Survey
* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project
Download Thames Valley Chemotherapy Regimens
Document related concepts
no text concepts found
Transcript
Thames Valley Thames Valley Chemotherapy Regimens Upper Gastrointestinal Cancer Thames Valley Notes from the editor These protocols are available on the Network website www.tvcn.nhs.uk. Any correspondence about the protocols should be addressed to: Sally Coutts, Cancer Pharmacist, Thames Valley email: [email protected] Tel: 01865 857166 Acknowledgements These regimens have been compiled by the Network Pharmacy Group in collaboration with the Upper GI TSSG with key contribution from Dr Kinnari Patel, Consultant Oncologist, OUH Dr James Gildersleve, Consultant Oncologist, RBFT Dr Nicola Warner, Consultant Oncologist, OUH Dr Claire Blesing, Consultant Oncologist, OUH Karen Carter, Pharmacist, RBFT Jane Gibbard, Pharmacist, OUH Alison Ashman, Formerly Lead Pharmacist Thames Valley Cancer Network © Thames Valley Cancer Network. All rights reserved. Not to be reproduced in whole or in part without the permission of the copyright owner. Chemotherapy Regimens – Upper GI Cancer 2 Thames Valley Thames Valley Chemotherapy Regimens Upper Gastrointestinal Cancer Network Chemotherapy regimens used in the management of Upper Gastrointestinal Cancer Date published: June 2013 Date of review: June 2015 Chemotherapy Regimens Name of protocol List of amendments to this version Cisplatin + Fluorouracil (CF 80 pre-op) infusor ECF EC capecitabine (ECX) Epirubicin, oxaliplatin and capecitabine (EOX) FAM Trastuzumab, capecitabine and cisplatin Cisplatin + Fluorouracil (CF 75 RT) + RT infusor Cisplatin + Capecitabine + RT Docetaxel 75 Mitomycin + Fluorouracil (MF) Paclitaxel 7 day Carboplatin 7 day + RT Capecitabine + RT Gemcitabine Gemcitabine + RT Gemcitabine and capecitabine Fluorouracil continuous + RT FOLFIRINOX Oxaliplatin and capecitabine Cisplatin + Modified De Gramont infusor daypatient Epirubicin Gemcitabine (1000) + Cisplatin (25) daypatient Pre and post-hydration regimen Common Toxicity criteria Indication Oesophagus Gastric and oesophagus Gastric and oesophagus Gastric and oesophagus Gastric and oesophagus Gastric oesophageal junction Oesophagus Oesophagus Gastric and oesophagus Gastric and oesophagus Oesophagus Pancreas Pancreas Pancreas Pancreas Pancreas Pancreas Pancreas Gallbladder Gallbladder Gallbladder cholangiocarcinoma Page 4 5 7 10 14 17 19 23 25 28 30 32 34 37 39 41 44 46 48 51 53 55 57 58 Chemotherapy Regimens – Upper GI Cancer 3 Thames Valley List of amendments in this version Regimen type: Upper GI Tumours Date due for review: June 2015 Previous Version number: 3.3 This version number: 3.4 Table 1 Amendments Page Action Type Amendment Made/ asked by Table 2 New protocols to be approved and checked by TSSG included in this version Name of regimen Indication Reason / Proposer Capecitabine + RT Carboplatin Paclitaxel weekly +RT Pancreas Oesophageal Dr Mukherjee Dr Mukherjee Chemotherapy Regimens – Upper GI Cancer 4 Thames Valley CISPLATIN + FLUOROURACIL (CF 80 pre-op) infusor Indication: Pre-operative chemotherapy for cancer of the oesophagus DRUG REGIMEN Day 1 Pre hydration CISPLATIN 80mg/m2 in 1000ml sodium chloride 0.9% infusion over 2 hours (daypatient) FLUOROURACIL 4000mg/m2 infusion over 96 hours via an infusor Post hydration Cycle Frequency: Repeat day 21 (2 cycles only) DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min consider carboplatin or switch to an appropriate oxaliplatin containing regimen Discuss with Consultant re omission / substitution If patient complains of tinnitus, tingling of fingers and/or toes discuss with SpR or Consultant before administration. Fluorouracil: Not to go ahead if cisplatin is contra-indicated/discontinued Consider dose reduction in severe renal impairment only. Bilirubin <85micromol/L or ALT/AST <180 give 100% dose Bilirubin >85micromol/L or ALT/AST >180 omit Treatment delays If Neutrophils <1.5x109/L and/or the platelet count <100x109/L delay the second course by one week, recheck blood count. If satisfactory (>1.5x109/L and >100x109/L) give 75% dose Cisplatin and 5FU. If not satisfactory delay by a further week and recheck blood count, if satisfactory (>1.5x109/L and >100x109/L) then give 50% dose Cisplatin and 5FU. If still unsatisfactory after 2 week delay chemotherapy should be discontinued. CF infusor Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 5 Thames Valley INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 Plt x 109/L ≥100 <100 ≥1.5 <1.5 Neutrophils x 109/L ≥3.5 <3.5 WBC x 109/L Creatinine clearance (GFR) calculated or EDTA or 24 hour urine collection at the Consultant discretion. (Cisplatin) 2) Non-urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per inpatient schedule at the end of TVCN protocols. If fluid balance is > 2L positive after 8 hours post hydration OR if patient gains >2kg in weight or urine output <100ml//hour during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV ANTI-EMETIC POLICY Highly emetogenic day 1 Low emetogenic risk days 2, 3, 4 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds Mucositis – use routine mouthcare Diarrhoea –treat with codeine or loperamide Nephrotoxicity – ensure adequate pre and post hydration is prescribed Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease or those who develop chest pain during treatment with fluorouracil. REFERENCES 1. Lancet 2002. May 18; 359 (9319): 1727-33 CF infusor Upper GI TSSG Chair Authorisation: Date: Page 2 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 6 Thames Valley ECF Indication: Advanced gastric, oesophageal cancer, adjuvant gastric cancer and unknown adenocarcinoma Unknown primary if appropriate DRUG REGIMEN EPIRUBICIN 50mg/m2 IV bolus Pre-hydration CISPLATIN 60mg/m2 in 1000ml sodium chloride 0.9% infusion over 2 hours Post hydration FLUOROURACIL 200mg/m2/24 hours continuous infusion for 7 days, Day 8 FLUOROURACIL 200mg/m2/24 hours continuous infusion for 7 days Day 15 FLUOROURACIL 200mg/m2/24 hours continuous infusion for 7 days and continue for 21 days after last Epirubicin / Cisplatin admission. Day 1 Note on cycle Fluorouracil should start 4 hours prior to cisplatin. Cycle Frequency: Every 21 days up to 6 cycles Adjuvant 3 cycles pre-op and 3 cycles post-op DOSE MODIFICATIONS Platelets x 109/L Neutrophils x 109/L WBC x 109/L Dose modification ECF 100 1.5 2.0 50-100 0.5-1.5 1.0-1.9 25-49 <0.5 <1.0 Full dose Stop 5FU, delay Cisplatin and epirubicin until recovery. Restart give 75% epirubicin dose on subsequent cycles Stop 5FU, delay Cisplatin and epirubicin until recovery. Restart 5FU at full dose, give 50% epirubicin dose on subsequent cycles Upper GI TSSG Chair Authorisation: Date: Page 1 of 3 <25 Stop 5FU, delay Cisplatin and epirubicin until recovery. Restart 5FU at full dose BUT omit epirubicin from subsequent cycles Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 7 Thames Valley Epirubicin: Bilirubin 24-51micromol/L give 50% dose Bilirubin 51-85micromol/L give 25% dose Bilirubin >85micromol/L omit Dose reduce in severe renal impairment. Neutropenia / fever infection Neutrophils 0.5-1.0 give 75% dose of epirubicin for subsequent cycles Neutrophils <0.5 give 50% dose of epirubicin for subsequent cycles Maximum lifetime dose = 650mg/m2 (in combination with thoracic radiotherapy or previous anthracyclines = 1000 mg/m2 (with normal cardiac function) Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min consider carboplatin or switch to an appropriate oxaliplatin containing regimen Discuss with Consultant re omission / substitution Consider substitution with carboplatin AUC 4 or 5 every 4 weeks if cisplatin is contra-indicated If patient complains of tinnitus, tingling of fingers and/or toes discuss with SpR or Consultant before administration. Fluorouracil: Consider dose reduction in severe renal impairment only. Bilirubin <85micromol/L or ALT/AST <180 give 100% dose Bilirubin > 85micromol/L or ALT/AST >180 omit Diarrhoea and/or mucositis Grade 2 toxicity – 1 week break from 5FU then restart at 150mg/m2/day Grade 3 toxicity – stop 5FU until symptoms resolve, then restart at 100mg/m2/day Grade 4 toxicity – stop 5FU until symptoms resolve, then restart at 50mg/m2/day ECF Upper GI TSSG Chair Authorisation: Date: Page 2 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 8 Thames Valley INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 Plt x 109/L ≥100 <100 Neutrophils x 109/L ≥1.5 <1.5 Creatinine clearance (GFR) calculated or EDTA or 24 hour urine collection at the Consultant discretion. (Cisplatin) 2) Non-urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre-and post-hydration prescribed as per TVCN protocols. Daypatient: If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 20 - 40mg Furosemide PO/IV or 200ml Mannitol 10% IV Inpatient: If fluid balance is > 2L positive after 8 hours post hydration OR urine output is < 100ml/hour during IV administration post Cisplatin give 20 ¬ 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV ANTI-EMETIC POLICY Highly emetogenic day 1 Low emetogenic risk days 2 to 21 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds if symptoms fail to improve then stop 5FU for 1 week then restart at 150mg/m2/day. Mucositis – see dose modifications use routine mouthcare Diarrhoea – see dose modifications treat with loperamide or codeine Nephrotoxicity – ensure adequate pre and post hydration is prescribed Cardiotoxicity – monitor cardiac function. To minimise risk of anthracycline induced cardiac failure signs of cardiotoxicity e.g. cardiac arrhythmias, pericardial effusion, tachycardia with fatigue. Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease or those who develop chest pain during treatment with fluorouracil. REFERENCES 1. Waters JS et al. Br J Cancer 1999; 80: 269-72 ECF Upper GI TSSG Chair Authorisation: Date: Page 3 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 9 Thames Valley EC CAPECITABINE (ECX) Indication: Advanced gastric, oesophageal cancer, adjuvant and neoadjuvant gastric cancer and unknown adenocarcinoma, adjuvant gastric and type 3 gastro oesophageal junction cancer. Unknown primary if appropriate DRUG REGIMEN Day 1 EPIRUBICIN 50mg/m2 IV bolus Pre-hydration CISPLATIN 60mg/m2 in 1000ml sodium chloride 0.9% infusion over 2 hours Post hydration CAPECITABINE 1250mg/m² daily in 2 divided doses for 21 days Cycle frequency: Every 21 days (up to 6 cycles). Adjuvant chemo, give 3 cycles pre-op and 3 cycles post-op Note: Tablets are only available as 150mg and 500mg tablets Note: on cycle 1 capecitabine should start prior to cisplatin. DOSE MODIFICATIONS Platelets x 109/L Neutrophils x 109/L WBC x 109/L Dose modification 100 1.5 2.0 Full dose 50-100 0.5-1.5 1.0-1.9 Stop capecitabine, delay Cisplatin and epirubicin until recovery. Restart capecitabine at full dose, give 75% epirubicin dose on subsequent cycles 25-49 <0.5 <1.0 Stop capecitabine, delay Cisplatin and epirubicin until recovery. Restart capecitabine at full dose, give 50% epirubicin dose on subsequent cycles <25 Stop capecitabine, delay Cisplatin and epirubicin until recovery. Restart capecitabine at full dose BUT omit epirubicin from subsequent cycles Epirubicin: Bilirubin 24-51 micromol/L give 50% dose Bilirubin 51-85 micromol/L give 25% dose Bilirubin >85 micromol/L omit Dose reduce in severe renal impairment. Neutropenia / fever infection Neutrophils 0.5-1.0 give 75% dose of epirubicin for subsequent cycles Neutrophils <0.5 give 50% dose of epirubicin for subsequent cycles Maximum lifetime dose = 1000mg/m2 (with normal cardiac function) = 650mg/m2 (in combination with thoracic radiotherapy or previous anthracyclines EC capecitabine Upper GI TSSG Chair Authorisation: Date: Page 1 of 3 Published: June 2013 Version 3.4 Review: June 2015June Chemotherapy Regimens – Upper GI Cancer 10 2015 Thames Valley Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min consider carboplatin or switch to an appropriate oxaliplatin containing regimen Discuss with Consultant re omission / substitution Consider substitution with carboplatin AUC 4 or 5 every 4 weeks if cisplatin is contra-indicated If patient complains of tinnitus, tingling of fingers and/or toes discuss with SpR or Consultant before administration. Capecitabine: Check CrCl prior to every cycle CrCl (ml/min) > 50 give 100% dose CrCl (ml/min) 30 - 50 give 75% dose CrCl (ml/min) < 30 contraindicated (2) Hepatic impairment – SPC recommends interruption of capecitabine therapy if treatment related elevations in bilirubin of > 3 x ULN or ALT/AST > 2.5 x ULN occur. Treatment may be resumed when bilirubin decreases to < 3 x ULN or hepatic aminotransferases decrease to < 2.5 x ULN. Please refer to summary of product characteristics for detailed guidance on dose modification due to toxicity (including plantar palmar, erythema and gastrointestinal toxicity). Brief guidance on initial dose modifications at the first appearance of toxicity is given below. the Summary of Product Characteristics (SPC) which can be viewed at www.medicines.org.uk. This includes details on how to manage 2nd and subsequent appearance of toxicities. Toxicity can be managed by symptomatic treatment and/or modification of the dose (treatment interruption or dose reduction). Once the dose has been reduced it should not be increased at a later time. Dose limiting toxicities include diarrhoea, abdominal pain, nausea, stomatitis and handfoot syndrome. EC capecitabine Upper GI TSSG Chair Authorisation: Date: Page 2 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 11 Thames Valley Toxicity Grades * Grade 1 * Grade 2 - 1st appearance - 2nd appearance - 3rd appearance - 4th appearance * Grade 3 - 1st appearance - 2nd appearance - 3rd appearance * Grade 4 - 1st appearance Dose changes within a treatment cycle Maintain dose level Dose adjustment for next cycle/dose (% of starting dose) Maintain dose level Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Discontinue treatment permanently 100% 75% 50% Not applicable Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Discontinue treatment permanently 75% 50% Not applicable Discontinue permanently OR If physician deems it to be in the patient's best interest to continue, interrupt until resolved to grade 0-1 - 2nd appearance Discontinue permanently 50% Not applicable INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 Plt x 109/L ≥100 <100 ≥1.5 <1.5 Neutrophils x 109/L Creatinine clearance (GFR) calculated or EDTA or 24 hour urine collection at the Consultant discretion. (Cisplatin) 2) Non-urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre-and post-hydration prescribed as per TVCN protocols. Daypatient: If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 20 - 40mg Furosemide PO/IV or 200ml Mannitol 10% IV Inpatient: If fluid balance is > 2L positive after 8 hours post hydration OR urine output is < 100ml/hour during IV administration post Cisplatin give 20 ¬ 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV Patients taking phenytoin concomitantly with capecitabine should be regularly monitored for increased phenytoin plasma concentrations. Capecitabine enhances the anticoagulant effects of warfarin. Patients taking warfarin concomitantly with capecitabine must have regular monitoring of INR. EC capecitabine Upper GI TSSG Chair Authorisation: Date: Page 2 of 3 Published: June 2013 Version 3.4 Chemotherapy Regimens – Upper GI Cancer 12 Review: June 2015June 2015 Thames Valley ANTI-EMETIC POLICY Highly emetogenic day 1 Low emetogenic risk days 2 to 21 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds Mucositis – see dose modifications Diarrhoea – see dose modifications Nephrotoxicity – ensure adequate pre and post hydration is prescribed Cardiotoxicity – monitor cardiac function. To minimise risk of anthracycline induced cardiac failure signs of cardiotoxicity e.g. cardiac arrhythmias, pericardial effusion, tachycardia with fatigue. REFERENCES 1. REAL 2 trial (arm 3) 2. ST03 trial EC capecitabine Upper GI TSSG Chair Authorisation: Date: Page 3 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 13 Thames Valley EPIRUBICIN, OXALIPLATIN and CAPECITABINE (EOX) Indication: Advanced gastric, oesophageal cancer, adjuvant gastric cancer and unknown adenocarcinoma Unknown primary if appropriate DRUG REGIMEN Day 1 EPIRUBICIN 50mg/m2 IV bolus OXALIPLATIN 130mg/m2 in 500ml glucose 5% infusion over 2 hours Flush with glucose 5% after infusion CAPECITABINE 1250mg/m² daily in 2 divided doses for 21 days Cycle frequency: Every 21 days (up to 6 cycles). Note: Tablets are only available as 150mg and 500mg tablets therefore dose must be rounded appropriately Oxaliplatin should always be administered before fluoropyrimidines. DOSE MODIFICATIONS Refer to the REAL-2 protocol Previous neutropenic sepsis, discuss with SpR or Consultant, Symptoms including diarrhoea, mucositis and leucopenia, discuss with SpR or Consultant. Epirubicin: Bilirubin 24-51 micromol/L give 50% dose Bilirubin 51-85 micromol/L give 25% dose Bilirubin >85 micromol/L omit Neutropenia / fever infection Neutrophils 0.5-1.0 give 75% dose of epirubicin for subsequent cycles Neutrophils <0.5 give 50% dose of epirubicin for subsequent cycles Maximum lifetime dose = 1000mg/m2 (with normal cardiac function) = 650mg/m2 (in combination with thoracic radiotherapy or previous anthracyclines Oxaliplatin: If persistent sensory symptoms occur, withdraw treatment GFR >20ml/min give 100% dose and adjust according to toxicity GFR <20ml/min dose reduce [4] Hepatic impairment: Probably no dose reduction necessary Clinical decision If patients develop acute laryngopharyngeal dysaesthesia infuse the next cycle over 6 hours. If symptoms persist give 80% dose. EOX cape Colorectal TSSG Chair Authorisation: Date: Page 1 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 14 Thames Valley Capecitabine: Check CrCl prior to every cycle CrCl (ml/min) >50 give 100% CrCl (min/min) 30 - 50 give 75% dose CrCl (ml/min) <30 capecitabine is contraindicated (2) Hepatic impairment – SPC recommends interruption of capecitabine therapy if treatment related elevations in bilirubin of > 3 x ULN or ALT/AST > 2.5 x ULN occur. Treatment may be resumed when bilirubin decreases to < 3 x ULN or hepatic aminotransferases decrease to < 2.5 x ULN. Please refer to summary of product characteristics for detailed guidance on dose modification s due to toxicity (including plantar palmar, erythema and gastrointestinal toxicity). Brief guidance on initial dose modifications at the first appearance of toxicity is given below. the Summary of Product Characteristics (SPC) which can be viewed at www.medicines.org.uk. This includes details on how to manage 2nd and subsequent appearance of toxicities. Toxicity can be managed by symptomatic treatment and/or modification of the dose (treatment interruption or dose reduction). Once the dose has been reduced it should not be increased at a later time. Dose limiting toxicities include diarrhoea, abdominal pain, nausea, stomatitis and handfoot syndrome. Toxicity Grades * Grade 1 * Grade 2 - 1st appearance - 2nd appearance - 3rd appearance - 4th appearance * Grade 3 - 1st appearance - 2nd appearance - 3rd appearance * Grade 4 - 1st appearance Dose changes within a treatment cycle Maintain dose level Dose adjustment for next cycle/dose (% of starting dose) Maintain dose level Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Discontinue treatment permanently 100% 75% 50% Not applicable Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Discontinue treatment permanently 75% 50% Not applicable Discontinue permanently OR If physician deems it to be in the patient's best interest to continue, interrupt until resolved to grade 0-1 - 2nd appearance Discontinue permanently EOX cape Colorectal TSSG Chair Authorisation: Date: 50% Not applicable Page 2 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 15 Thames Valley INVESTIGATIONS Routine Blood tests 1. Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 ≥75 <75 Plt x 109/L ≥1.5 <1.5 Neutrophils x 109/L 51 2. GFR assessed using Cr-EDTA result or calculated creatinine clearance at the Consultant’s discretion. 3. LFTs Non-urgent Blood tests Tests relating to disease response/progression. CONCURRENT MEDICATIONS Patients taking phenytoin concomitantly with capecitabine should be regularly monitored for increased phenytoin plasma concentrations. Capecitabine enhances the anticoagulant effects of warfarin. Patients taking warfarin concomitantly with capecitabine must have regular monitoring of INR. ANTI-EMETIC POLICY Highly emetogenic day 1 Low emetogenic risk days 2 to 21 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds. Diarrhoea – treat with loperamide or codeine Peripheral sensory neuropathy and laryngeal spasm – avoid cold drinks and touching cold items Cardiotoxicity – monitor cardiac function. To minimise risk of anthracycline induced cardiac failure signs of cardiotoxicity e.g. cardiac arrhythmias, pericardial effusion, tachycardia with fatigue. Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease or those who develop chest pain during treatment with fluorouracil. REFERENCES 1. REAL 2 trial (arm 4) 2. REAL 3 standard arm EOX cape Colorectal TSSG Chair Authorisation: Date: Page 3 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 16 Thames Valley FAM Indication: Advanced gastric or oesophageal cancer (if performance status is not good enough for ECF) DRUG REGIMEN Day 1 FLUOROURACIL 500mg/m2 IV bolus DOXORUBICIN 30mg/m2 IV bolus MITOMYCIN 10mg/m2 IV bolus Day 22 FLUOROURACIL 500mg/m2 IV bolus DOXORUBICIN 30mg/m2 IV bolus Cycle Frequency: Every 42 days for 3 cycles DOSE MODIFICATIONS Doxorubicin: Dose reduce in severe renal impairment. Bilirubin 20-50micromol/L give 50% dose Bilirubin 51-85micromol/L give 25% dose Bilirubin >85micromol/L omit If ALT/AST is 2-3 x ULN give 75% dose If ALT/AST is >3 x ULN give 50% dose Maximum cumulative dose = 450mg/m2 (in normal cardiac function) = 400mg/m2 (in combination with thoracic radiation treatment or Cyclophosphamide or in patients with cardiac risk factors) Fluorouracil: Consider dose reduction in severe renal impairment only. Bilirubin <85micromol/L or ALT/AST <180 give 100% dose Bilirubin >85micromol/L or ALT/AST >180 omit INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 Plt x 109/L ≥100 <100 ≥1.5 <1.5 Neutrophils x 109/L FAM Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: July 2012 Review: Version 3.2 July 2014 Chemotherapy Regimens – Upper GI Cancer 17 Thames Valley 2) Non-urgent blood tests Tests relating to disease response/progression ECG (possible ECHO) required if patient has pre-existing cardiac disease (Doxorubicin) CONCURRENT MEDICATION ANTI-EMETIC POLICY Moderately emetogenic ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds Mucositis – use routine mouthcare Diarrhoea – treat with codeine or loperamide Cardiotoxicity – monitor cardiac function. To minimise risk of anthracycline induced cardiac failure signs of cardiotoxicity e.g. cardiac arrhythmias, pericardial effusion, tachycardia with fatigue. Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease or those who develop chest pain during treatment with fluorouracil. REFERENCES 1. J Clin Onc 1997; 5 (No 1): 277-284 FAM Upper GI TSSG Chair Authorisation: Date: Page 2 of 2 Published: July 2012 Review: Version 3.2 July 2014 Chemotherapy Regimens – Upper GI Cancer 18 Thames Valley TRASTUZUMAB, CISPLATIN and CAPECITABINE Indication: HER2+ve metastatic adenocarcinoma of stomach or gastrointestinal oesophageal junction. NICE guidance - www.nice.org.uk Trastuzumab, in combination with cisplatin and capecitabine or 5-fluorouracil, is recommended as an option for the treatment of people with human epidermal growth factor receptor 2 (HER2)positive metastatic adenocarcinoma of the stomach or gastro-oesophageal junction who: have not received prior treatment for their metastatic disease and have tumours expressing high levels of HER2 as defined by a positive immunohistochemistry score of 3 (IHC3 positive). DRUG REGIMEN Pre-hydration CISPLATIN 80mg/m2 in 1000ml sodium chloride 0.9% IV infusion over 2 hours Post hydration Days 1 to 14 CAPECITABINE 1000mg/m2 po twice daily Day 1 Cycle Frequency: Every 21 days for 6 cycles Day 2 TRASTUZUMAB 8mg/kg in 250ml sodium chloride 0.9% IV infusion cycle 1 Day 1 TRASTUZUMAB 6mg/kg in 250ml sodium chloride 0.9% IV infusion cycles 2 to 18 Cycle Frequency: Every 21 days until disease progression starting on cycle 1 of cisplatin and capecitabine DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min consider carboplatin or switch to an appropriate oxaliplatin containing regimen Discuss with Consultant re omission / substitution If patient complains of tinnitus, tingling of fingers and/or toes discuss with SpR or Consultant before administration. Trastuzumab cisplatin capecitabine Upper GI TSSG Chair Authorisation: Date: Page 1 of 4 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 19 Thames Valley Capecitabine: Check CrCl prior to every cycle CrCl (ml/min) >50 give 100% dose CrCl (ml/min) 30 -50 give 75% dose CrCl (ml/min) <30 contraindicated Hepatic impairment – SPC recommends interruption of capecitabine therapy if treatment related elevations in bilirubin of > 3 x ULN or ALT/AST > 2.5 x ULN occur. Treatment may be resumed when bilirubin decreases to < 3 x ULN or hepatic aminotransferases decrease to < 2.5 x ULN. Please refer to summary of product characteristics (SPC) for detailed guidance on dose modifications due to toxicity (including plantar palmar, erythema and gastro-intestinal toxicity). Toxicity can be managed by symptomatic treatment and/or modification of the dose (treatment interruption or dose reduction). Once the dose has been reduced it should not be increased at a later time. Dose limiting toxicities include diarrhoea, abdominal pain, nausea, stomatitis and handfoot syndrome. Toxicity Grades * Grade 1 * Grade 2 - 1st appearance - 2nd appearance - 3rd appearance - 4th appearance * Grade 3 - 1st appearance - 2nd appearance - 3rd appearance * Grade 4 - 1st appearance Dose changes within a treatment cycle Maintain dose level Dose adjustment for next cycle/dose (% of starting dose) Maintain dose level Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Discontinue treatment permanently 100% 75% 50% Not applicable Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Discontinue treatment permanently 75% 50% Not applicable Discontinue permanently OR if physician deems it to be in the patient's best interest to continue, interrupt until resolved to grade 0-1 - 2nd appearance Discontinue permanently Trastuzumab cisplatin capecitabine Upper GI TSSG Chair Authorisation: Date: 50% Not applicable Page 2 of 4 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 20 Thames Valley Trastuzumab: No dose reduction or cessation of Trastuzumab is required if patient has acute reversible neutropenia. If trastuzumab infusion is delayed by more than 7 days the patient should be reloaded at 8mg/kg. Continuation and discontinuation of trastuzumab based on interval LVEF assessment If LVEF <44 hold trastuzumab, repeat LVEF in 3 weeks. If repeat LVEF <44 or LVEF 45-49 and >10 points from baseline then stop trastuzumab. If repeat LVEF 45-49 and <10 points from baseline or LVEF >49 resume trastuzumab. If LVEF 45-49 and >10 EF points from baseline hold trastuzumab, repeat LVEF in 3 weeks. If repeat LVEF <44 or LVEF 45-49 and >10 points from baseline stop trastuzumab. If repeat LVEF 45-49 and <10 points from baseline or LVEF >49 resume trastuzumab. If LVEF > 50 or LVEF 45-49 and <10 EF points from baseline continue trastuzumab. New LVEF assessment results should be available by the day of the next scheduled trastuzumab administration and a decision to give or hold the dose must be made based on this algorithm. INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 9 Plt x 10 /L ≥100 <100 ≥1.5 <1.5 Neutrophils x 109/L Creatinine clearance (GFR) calculated or EDTA or 24 hour urine collection at the Consultant's discretion. (Cisplatin) 2) Non-urgent blood tests - Tests relating to disease response / progression - Baseline weight and every 3 months - Monitor cardiac function (ECG/ECHO/MUGA) of all patients before and during treatment, aiming for assessments every 3 months. CONCURRENT MEDICATION Trastuzumab infusion related chills and/or fevers – treat with paracetamol and chlorphenamine. Patients taking phenytoin concomitantly with capecitabine should be regularly monitored for increased phenytoin plasma concentrations. Capecitabine enhances the anticoagulant effects of warfarin. Patients taking warfarin concomitantly with capecitabine must have regular monitoring of INR Give mouthcare and bowel support regimen as per Upper GI protocol Trastuzumab cisplatin capecitabine Upper GI TSSG Chair Authorisation: Date: Page 2 of 4 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 21 Thames Valley ANTI-EMETIC POLICY High emetic risk day 1 cycles 1 to 6 Low emetic risk days 2 to 13 cycles 1 to 6 Minimal emetic risk cycles 7 to 18 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Cardiotoxicity - monitor cardiac function. Special attention is advisable in treating patients with a history of heart disease, arrhythmias or angina pectoris or those who develop chest pain during treatment with capecitabine. Trastuzumab infusion related chills and/or fevers are commonly observed during the first infusion (but infrequently with subsequent infusions). Other symptoms may include nausea, hypertension, vomiting, pain, rigors, headache, cough, dizziness, rash, and asthenia. Some adverse reactions to trastuzumab infusion including dyspnoea, hypotension, wheezing, bronchospasm, supraventricular tachyarrhythmia, reduced oxygen saturation and respiratory distress can be serious and potentially fatal. If symptoms of back ache, nausea or vomiting, do a set of obs. Give hydrocortisone 100mg IV, chlorphenamine 10mg IV. Hand foot syndrome: Palmer Plantar causing red palms and soles - treat with pyridoxine 50mg tds Diarrhoea - treat with loperamide or codeine Mucositis - see dose modifications Nephrotoxicity - ensure adequate pre- and post- hydration is prescribed REFERENCES Trastuzumab cisplatin capecitabine Upper GI TSSG Chair Authorisation: Date: Page 2 of 4 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 22 Thames Valley CISPLATIN + FLUOROURACIL (CF 75 RT) concurrent with radical radiotherapy infusor Indication: Localised oesophageal carcinoma DRUG REGIMEN Day 1 Prehydration CISPLATIN 75mg/m2 in 1000ml sodium chloride 0.9% infusion over 2 hours FLUOROURACIL 4000mg/m2 over 96 hours via an infusor Posthydration Cycle Frequency: Week 1, 5 (with radiotherapy week 1 to 5 inc) and then week 9 and 13 DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min consider carboplatin or switch to an appropriate oxaliplatin containing regimen If patient complains of tinnitus, tingling of fingers and/or toes discuss with SpR or Consultant before administration Fluorouracil: Discuss with consultant whether 5FU to go ahead if cisplatin is contra-indicated/discontinued. Consider dose reduction in severe renal impairment only. Bilirubin <85micromol/L or ALT/AST <180 give 100% dose Bilirubin > 85micromol/L or ALT/AST >180 omit Treatment delays If Neutrophils <1.5x109/L and/or the platelet count <100x109/L delay the second course by one week, recheck blood count. If satisfactory (>1.5x109/L and >100x109/L) give 75% dose Cisplatin and 5FU If not satisfactory delay by a further week and recheck blood count, if satisfactory (>1.5x109/L and >100x109/L) then give 50% dose Cisplatin and 5FU. If still unsatisfactory after 2 week delay chemotherapy should be discontinued. CF + RT infusor Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 23 Thames Valley INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 Plt x 109/L ≥100 <100 Neutrophils x 109/L ≥1.5 <1.5 Creatinine clearance (GFR) calculated or EDTA or 24 hour urine collection at the Consultant discretion. (Cisplatin) 2) Non-urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Prescribe mouth and bowel support. Ensure adequate pre-and post-hydration prescribed as per TVCN protocols. Daypatient: If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 20 - 40mg Furosemide PO/IV or 200ml Mannitol 10% IV Inpatient: If fluid balance is > 2L positive after 8 hours post hydration OR urine output is < 100ml/hour during IV administration post Cisplatin give 20 ¬ 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV ANTI-EMETIC POLICY Highly emetogenic. day 1 Low emetogenic risk days 2, 3, 4 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds Mucositis – use routine mouthcare. Discuss dose reduction if severe. Diarrhoea – treat with codeine or loperamide, Discuss dose reduction if severe Nephrotoxicity – ensure adequate pre and post hydration is prescribed Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease, arrhythmias or angina pectoris or those who develop chest pain during treatment with fluorouracil. REFERENCES 1. J Clin Onc 1997; 5 (No 1): 277-284 CF + RT infusor Upper GI TSSG Chair Authorisation: Date: Page 2of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 24 Thames Valley CISPLATIN + CAPECITABINE concurrent with radical radiotherapy Indication: Oesophageal carcinoma (SCOPE-1 control arm) DRUG REGIMEN Day 1 Prehydration CISPLATIN 60mg/m2 in 1000ml sodium chloride 0.9% infusion over 2 hours CAPECITABINE 625mg/m2 po twice daily for 21 days Posthydration Cycle Frequency: every 21 days, 2 cycles followed by 2 cycles with concurrent RT DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 50% dose GFR <45ml/min Consider carboplatin or switch to an appropriate oxaliplatin containing regimen If patient complains of tinnitus, tingling of fingers and/or toes discuss with SpR or Consultant before administration Capecitabine: GFR >51ml/min give 100% dose GFR 30-50ml/min give 75% dose GFR < 30ml/min omit dose Cisplatin capecitabine RT Upper GI TSSG Chair Authorisation: Date: Page 1 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 25 Thames Valley Treatment delays Capecitabine dose reduction schedule for non-haematological toxicities. Grade 1: during a course -> Maintain dose level, for next cycle -> Maintain dose level Grade 2 1st appearance: during a course interrupt until resolved to grade 0-1, for next cycle -> 100% dose 2nd appearance: during a course interrupt until resolved to grade 0-1, for next cycle -> 75% dose 3rd appearance: during a course interrupt until resolved to grade 0-1, for next cycle -> 50% dose 4th appearance: during a course discontinue treatment permanently Grade 3 1st appearance: during a course interrupt until resolved to grade 0-1, for next cycle -> 75% dose 2nd appearance: during a course interrupt until resolved to grade 0-1, for next cycle -> 50% dose 3rd appearance: during a course discontinue treatment permanently Grade 4 1st appearance: during a course discontinue permanently or If physician deems it to be in the patient’s best interest to continue, interrupt until resolved to grade 0-1after discussion with Chief Investigator, for next cycle -> 50% dose INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 9 Plt x 10 /L ≥100 <100 ≥1.5 <1.5 Neutrophils x 109/L Creatinine clearance (GFR) calculated or EDTA or 24 hour urine collection at the Consultant discretion. (Cisplatin) 2) Non-urgent blood tests Tests relating to disease response/progression Cisplatin capecitabine RT Upper GI TSSG Chair Authorisation: Date: Page 2 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 26 Thames Valley CONCURRENT MEDICATION Prescribe mouth and bowel support. Ensure adequate pre-and post-hydration prescribed as per TVCN protocols. Daypatient: If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 20 - 40mg Furosemide PO/IV or 200ml Mannitol 10% IV Inpatient: If fluid balance is > 2L positive after 8 hours post hydration OR urine output is < 100ml/hour during IV administration post Cisplatin give 20 ¬ 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV ANTI-EMETIC POLICY Highly emetogenic. day 1 Low emetogenic risk days 2 to 21 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds Mucositis – use routine mouthcare. Discuss dose reduction if severe. Diarrhoea – treat with codeine or loperamide, Discuss dose reduction if severe Nephrotoxicity – ensure adequate pre and post hydration is prescribed Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease, arrhythmias or angina pectoris or those who develop chest pain during treatment with fluorouracil. Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease, arrhythmias or angina pectoris or those who develop chest pain during treatment with capecitabine. REFERENCES 1. J Clin Onc 1997; 5 (No 1): 277-284 2. SCOPE 1 version 5.0 February 2010 Cisplatin capecitabine RT Upper GI TSSG Chair Authorisation: Date: Page 3 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 27 Thames Valley DOCETAXEL (75) Indication: Second line therapy for oesophago-gastric carcinoma DRUG REGIMEN Day 1 PREMEDICATION: DEXAMETHASONE 8 mg BD starting 24 hours before chemotherapy (or 20mg IV on day of chemotherapy) and 8mg bd post-chemotherapy for 2 days (for patients who are unable to tolerate high doses of steroids 4mg doses may be considered) DOCETAXEL 75mg/m2 infusion in 250ml sodium chloride 0.9% over 60 minutes Cycle Frequency: Every 21 days Number of cycles: Individualised but not usually more than 6 (subject to tolerance and response) DOSE MODIFICATIONS Discuss if severe cutaneous reactions, peripheral neuropathy or fluid retention after previous course. Patients who have both elevations of transaminase (ALT and/or AST) > 1.5 x ULN and ALP > 2.5 x ULN: the SPC recommended dose is 75mg/m2. Patients with serum bilirubin > ULN and/or ALT and AST > 3.5 x ULN associated with ALP > 6 x ULN: docetaxel should not be used unless strictly indicated. INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 < 10 9 Plt x 10 /L ≥100 < 100 ≥1.5 < 1.5 Neutrophils x 109/L 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure pre-medication is given. This can reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions Docetaxel Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: November 2012 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 28 Thames Valley ANTIEMETIC POLICY Low emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Discuss if severe cutaneous reactions, peripheral neuropathy or fluid retention after previous course. REFERENCES 1. Shepherd F et al. J Clin Oncol 2000; 18: 2095 2103. Fossella F et al. J Clin Oncol 2000; 18: 2354 2362 2. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic impairment. 2009, The North London Cancer Network. Docetaxel Upper GI TSSG Chair Authorisation: Date: Page 2 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 29 Thames Valley MITOMYCIN + FLUOROURACIL (MF) Indication: Second line therapy for gastric or oesophageal cancer after failure of platinum based chemotherapy DRUG REGIMEN MITOMYCIN 7mg/m2 IV bolus. FLUOROURACIL 300mg/m2/24 hours continuous infusion for 7 days via an infusor Day 8 FLUOROURACIL 300mg/m2/24 hours continuous infusion for 7 days via an infusor Day 15 FLUOROURACIL 300mg/m2/24 hours continuous infusion for 7 days via an infusor Day 1 Cycle Frequency: Mitomycin – repeat every 3 - 6 weeks according to blood count Fluorouracil – repeat day 21 for 6 cycles DOSE MODIFICATIONS Symptoms including diarrhoea, mucositis and leucopenia, discuss with Registrar or Consultant. Fluorouracil: Consider dose reduction in severe renal impairment only. Bilirubin <85micromol/L or ALT/AST <180 give 100% dose Bilirubin > 85micromol/L or ALT/AST >180 omit The 5FU course should be delayed for a week or until completely recovered in the event of either low blood counts (neutrophils <1.5x109 or platelets <100x109) or any persistent mucositis or diarrhoea. Non-haematological toxicity (diarrhoea, stomatitis) CTC Grade 0-1 2 3 4 Haematological toxicity: 0-2 (P=or>50 & N=or>1.0) 100% 80% 50% No further treatment (NFT) Platelets (P), 3 (P=25-49 or N=0.5-0.9) 80% 70% 50% NFT Neutrophils (N) 4 (P<25 or N<0.5) 50% 50% 50% NFT Mitomycin: GFR >10ml/min give 100% dose GFR <10ml/min give 75% dose MF Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 30 Thames Valley INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 Plt x 109/L ≥100 <100 ≥1.5 <1.5 Neutrophils x 109/L GFR assessed using 51Cr-EDTA result or calculated creatinine clearance at the Consultant’s discretion. 2) Non-urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION ANTI-EMETIC POLICY Low emetogenic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds Mucositis – use routine mouthcare. Discuss dose reduction if severe. Diarrhoea – treat with codeine or loperamide. Discuss dose reduction if severe. Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease, arrhythmias or angina pectoris or those who develop chest pain during treatment with fluorouracil. MF Upper GI TSSG Chair Authorisation: Date: Page 2 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 31 Thames Valley PACLITAXEL 7 day and CARBOPLATIN 7 day with RT Indication: Oesophageal cancer pre-operatively DRUG REGIMEN Day 1 PRE-MEDICATION 30 mins prior to infusion: DEXAMETHASONE 10-20mg IV bolus RANITIDINE 50mg IV bolus CHLORPHENAMINE 10mg IV bolus PACLITAXEL 80mg/m2 in 250ml sodium chloride 0.9% infusion over 1 hour (PVC free) CARBOPLATIN AUC 2* in 500ml glucose 5% infusion over 60 minutes Dose (mg) = (GFR + 25) x AUC Day 8 PRE-MEDICATION 30 mins prior to infusion: DEXAMETHASONE 10-20mg IV bolus RANITIDINE 50mg IV bolus CHLORPHENAMINE 10mg IV bolus PACLITAXEL 80mg/m2 in 250ml sodium chloride 0.9% infusion over 1 hour (PVC free) CARBOPLATIN AUC 2* in 500ml glucose 5% infusion over 60 minutes Dose (mg) = (GFR + 25) x AUC Day 15 PRE-MEDICATION 30 mins prior to infusion: DEXAMETHASONE 10-20mg IV bolus RANITIDINE 50mg IV bolus CHLORPHENAMINE 10mg IV bolus PACLITAXEL 80mg/m2 in 250ml sodium chloride 0.9% infusion over 1 hour (PVC free) CARBOPLATIN AUC 2* in 500ml glucose 5% infusion over 60 minutes Dose (mg) = (GFR + 25) x AUC *EDTA Ideally GFR is measured using 51Cr-EDTA then AUC = 2 *Calculated CrCl If GFR is calculated from serum creatinine then AUC = 3 Cycle Frequency: Every 28 days for 2 to 4 cycles. Patient may be changed to 21 day Paclitaxel and carboplatin according to response DOSE MODIFICATIONS Previous neutropenic sepsis, discuss with Consultant or Registrar Paclitaxel: If patient complains of tinnitus, tingling of fingers and/or toes or motor weakness discuss with Consultant or Registrar before administration. If grade II or > neuropathy, consider using reducing dose of paclitaxel Delay 1 week if day 1 neutrophil count < 1.5x109/L and / or platelet count is < 100x109/L. Myelosuppression is reasonably common consider dose reduction from 80 to 60 mg/m2 In the absence of Gilbert's syndrome: Bilirubin >51micromol/L stop treatment Paclitaxel carboplatin 7 day + RT Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: June 2013 Version 3.4 Review: June 2015 Chemotherapy Regimens – Upper GI Cancer 32 Thames Valley Carboplatin: If GFR = or < 20ml/min contraindicated INVESTIGATIONS 1) Blood results required before chemotherapy administration: Give Hb x g/dL ≥10 ≥100 Plt x 109/L Neutrophils x 109/L ≥1.5 Discuss <10 <100 <1.5 Liver function tests (LFTs). GFR assessed using 51Cr-EDTA result or calculated creatinine clearance the Consultant’s discretion. Patients with hydronephrosis or serum creatinine > 100 micromol/L need a serum creatinine checked every cycle. All patients have serum creatinine checked 1st and 4th cycle. 2) Non-urgent blood tests- Tests relating to disease response/progression CONCURRENT MEDICATION Anaphylaxis treatment should be prescribed if the patient has had an anaphylactic episode previously. DEXAMETHASONE 20mg IV bolus CHLORPHENAMINE 10mg IV bolus RANITIDINE 50mg IV bolus Carboplatin should be given at a slower rate e.g. 2-4 hours. ANTI-EMETIC POLICY Moderately emetogenic day 1 (routinely dexamethasone and metoclopramide is adequate but 5HT3 antagonist may be required if there is inadequate control). Mildly emetogenic day 8 and 15 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS 2% risk of severe hypersensitivity. Reactions range from mild hypotension (light-headedness) to full cardiac collapse (anaphylactic shock). Discontinue infusion and resuscitate appropriate to reaction. If reaction is mild and settles promptly (i.e. within 5-10mins), cautiously restart at a slower rate under close supervision. If further reactions occur stop treatment. Ototoxicity - monitor Neurotoxicity - monitor REFERENCES Paclitaxel carboplatin 7 day + RT Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: June 2013 Review: Version 3.4 June 2015 Chemotherapy Regimens – Upper GI Cancer 33 Thames Valley CAPECITABINE (5 day) with RT Indication: Locally advanced pancreatic cancer DRUG REGIMEN CAPECITABINE 830mg/m2 twice daily (1660mg/m2/day) for 5 days per week Tablets available as strengths of 150 mg and 500 mg. Cycle Frequency: for duration of radiotherapy (i.e. 28 days) DOSE MODIFICATIONS Capecitabine Consider giving 75% dose of capecitabine for patients >70 years depending on performance status Check CrCl prior to every cycle CrCl (ml/min) > 50 give 100% dose CrCl (ml/min 30 -50 give 75% dose CrCl (ml/min < 30 contraindicated Hepatic impairment – SPC recommends interruption of capecitabine therapy if treatment related elevations in bilirubin of > 3 x ULN or ALT/AST > 2.5 x ULN occur. Treatment may be resumed when bilirubin decreases to < 3 x ULN or hepatic aminotransferases decrease to < 2.5 x ULN. Please refer to summary of product characteristics for detailed guidance on dose modification s due to toxicity (including plantar palmar, erythema and gastrointestinal toxicity). Brief guidance on initial dose modifications at the first appearance of toxicity is given below. Users of these guidelines should also refer to the more detailed guidance contained within the Summary of Product Characteristics (SPC) which can be viewed at www.medicines.org.uk. This includes details on how to manage 2nd and subsequent appearance of toxicities. Toxicity can be managed by symptomatic treatment and/or modification of the dose (treatment interruption or dose reduction).Once the dose has been reduced it should not be increased at a later time. Dose limiting toxicities include diarrhoea, abdominal pain, nausea, stomatitis and handfoot syndrome. Capecitabine Upper GI TSSG Chair Authorisation: 5 day RT (pancreas) Date: Page 1 of 3 Published: June 2013 Review: Version 3.4 June2015 Chemotherapy Regimens – Upper GI Cancer 34 Thames Valley Toxicity Grades * Grade 1 * Grade 2 - 1st appearance - 2nd appearance - 3rd appearance - 4th appearance * Grade 3 - 1st appearance - 2nd appearance - 3rd appearance * Grade 4 - 1st appearance Dose changes within a treatment cycle Maintain dose level Dose adjustment for next cycle/dose (% of starting dose) Maintain dose level Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Discontinue treatment permanently 100% 75% 50% Not applicable Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Discontinue treatment permanently 75% 50% Not applicable Discontinue permanently OR if physician deems it to be in the patient's best interest to continue, interrupt until resolved to grade 0-1 - 2nd appearance Discontinue permanently 50% Not applicable INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Serum creatinine - GFR should be calculated or measured using EDTA CONCURRENT MEDICATION Patients taking phenytoin concomitantly with capecitabine should be regularly monitored for increased phenytoin plasma concentrations. Capecitabine enhances the anticoagulant effects of warfarin. Patients taking warfarin concomitantly with capecitabine must have regular monitoring of INR. ANTIEMETIC POLICY Low emetogenic risk Capecitabine Upper GI TSSG Chair Authorisation: 5 day RT (pancreas) Date: Page 2 of 3 Published: June 2013 Review: Version 3.4 June2015 Chemotherapy Regimens – Upper GI Cancer 35 Thames Valley ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds Diarrhoea – treat with loperamide or codeine Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease or those who develop chest pain during treatment with capecitabine. REFERENCES 1. SCALOP study Capecitabine Upper GI TSSG Chair Authorisation: 5 day RT (pancreas) Date: Page 3 of 3 Published: June 2013 Review: Version 3.4 June2015 Chemotherapy Regimens – Upper GI Cancer 36 Thames Valley GEMCITABINE Indication: Adjuvant and advanced pancreatic cancer NICE guidance – www.nice.org.uk Gemcitabine may be considered as a treatment option for patients with advanced or metastatic adenocarcinoma of the pancreas and a Karnofsky performance score of 50 or more, where first line chemotherapy is to be used DRUG REGIMEN Day 1 GEMCITABINE 1000mg/m2 in 250ml sodium chloride 0.9% infusion over 30 minutes Day 8 GEMCITABINE 1000mg/m2 in 250ml sodium chloride 0.9% infusion over 30 minutes Day 15 GEMCITABINE 1000mg/m2 in 250ml sodium chloride 0.9% infusion over 30 minutes Cycle Frequency: Every 28 days for 6 cycles DOSE MODIFICATIONS Gemcitabine: Do not give with concurrent radiotherapy. If patient has a serum creatinine > 150 micromol/L or CrCl <30ml/min consider dose reduction (Clinical decision). If bilirubin >27micromol/L initiate treatment with dose of 800mg/m2. Gemcitabine should be given with caution to patients with impaired hepatic function Neutrophils >1.5x109/L and platelets >100x109/L give 100% dose Neutrophils 0.5-1.5x109/L or platelets 50-100x109/L give 75% dose or delay based on clinical assessment Neutrophils <0.5x109/L or platelets <50x109/L delay treatment (Day 1) or omit treatment (Day 8 and 15) and give 75% dose for subsequent cycles once count has recovered Diarrhoea and/or mucositis Grade 2 toxicity – omit until toxicity resolved then restart at 100% dose Grade 3 toxicity – omit until toxicity resolved then restart at 75% dose Grade 4 toxicity – omit until toxicity resolved then restart at 50% dose Gemcitabine Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 37 Thames Valley INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 Plt x 109/L ≥100 <100 ≥1.5 <1.5 Neutrophils x 109/L 2) Non-urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION ANTI-EMETIC POLICY Low emetogenic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Diarrhoea – see dose modifications treat with loperamide or codeine Mucositis – see dose modifications use routine mouth care REFERENCES 1. Burris HA et al. J Clin Oncol 1997; 6: 2403-13 2. ESPAC-3 trial Gemcitabine Upper GI TSSG Chair Authorisation: Date: Page 2 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 38 Thames Valley GEMCITABINE with radiotherapy Indication: Locally advanced non-metastatic pancreatic cancer unable to receive capecitabine NICE guidance – www.nice.org.uk Gemcitabine may be considered as a treatment option for patients with advanced or metastatic adenocarcinoma of the pancreas and a Karnofsky performance score of 50 or more, where first line chemotherapy is to be used DRUG REGIMEN GEMCITABINE 300mg/m2 in 250ml sodium chloride 0.9% infusion over 30 minutes Day 1 to be prescribed to start on day 2 of radiotherapy (total planning target volume should be restricted to smaller than 800 CM3) Days 1, 8, 22 and 29 Cycle Frequency: For 1 cycle with radiotherapy DOSE MODIFICATIONS Gemcitabine: If patient has a serum creatinine > 150micromol/L or CrCl <30ml/min consider dose reduction (Clinical decision). Gemcitabine should be given with caution to patients with impaired hepatic function Neutrophils >=1.5 x 109/L and platelets >=100 x 109/L give 100% dose Neutrophils 1.0 - 1.49 x 109/L or platelets 75-99 x 109/L give 50% dose Neutrophils <1.0x109/L or platelets <75x109/L delay treatment by one week or until counts have completely recovered and give 50% dose for subsequent doses INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 9 Plt x 10 /L ≥100 <100 ≥1.5 <1.5 Neutrophils x 109/L 2) Non-urgent blood tests Tests relating to disease response/progression Liver function tests CONCURRENT MEDICATION Mouth & Bowel support Gemcitabine RT Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: June 2013 Version 3.4 Review: June 2015June 2015 Chemotherapy Regimens – Upper GI Cancer 39 Thames Valley ANTI-EMETIC POLICY Low emetogenic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Diarrhoea – see dose modifications treat with loperamide or codeine Mucositis – see dose modifications use routine mouth care REFERENCES 1. International archives of Medicine 2009 2:7-13 2. Huang et al IJROBP (2009) 73 (1): 159-165 Gemcitabine RT Upper GI TSSG Chair Authorisation: Date: Page 2 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 40 Thames Valley GEMCITABINE and CAPECITABINE Indication: Advanced pancreatic cancer NICE guidance – www.nice.org.uk Gemcitabine may be considered as a treatment option for patients with advanced or metastatic adenocarcinoma of the pancreas and a Karnofsky performance score of 50 or more, where first line chemotherapy is to be used NB Capecitabine has not been approved by TVCN or NICE for routine use. Named patient approval required prior to use DRUG REGIMEN Day 1 GEMCITABINE 1000mg/m2 in 250ml sodium chloride 0.9% infusion over 30 minutes CAPECITABINE 830mg/m2 twice daily (1660mg/m2/day) for 21 days followed by a 7 day rest Day 8 GEMCITABINE 1000mg/m2 in 250ml sodium chloride 0.9% infusion over 30 minutes Day 15 GEMCITABINE 1000mg/m2 in 250ml sodium chloride 0.9% infusion over 30 minutes Cycle Frequency: Every 28 days for 6 cycles NB capecitabine tablets are available in strengths of 150 mg and 500 mg. DOSE MODIFICATIONS Gemcitabine: Do not give with concurrent radiotherapy. If patient has a serum creatinine >150 micromol/L or CrCl <30ml/min consider dose reduction (Clinical decision). If bilirubin >27micromol/L initiate treatment with dose of 800mg/m2. Neutrophils >1.5x109/L and platelets >100x109/L give 100% dose Neutrophils 0.5-1.5x109/L or platelets 50-100x109/L give 75% dose or delay based on clinical assessment Neutrophils <0.5x109/L or platelets <50x109/L delay treatment (Day 1) or omit treatment (Day 8) and give 75% dose for subsequent cycles once count has recovered Diarrhoea and/or mucositis Grade 2 toxicity – omit until toxicity resolved then restart at 100% dose Grade 3 toxicity – omit until toxicity resolved then restart at 75% dose Grade 4 toxicity – omit until toxicity resolved then restart at 50% dose Gemcitabine Upper GI TSSG Chair Authorisation: and Capecitabine Date: Page 1 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 41 Thames Valley Capecitabine: Check CrCl prior to every cycle CrCl (ml/min) >50 give 100% dose CrCl (ml/min) 30 -50 give 75% dose CrCl (ml/min) <30 contraindicated Hepatic impairment – SPC recommends interruption of capecitabine therapy if treatment related elevations in bilirubin of >3 x ULN or ALT/AST >2.5 x ULN occur. Treatment may be resumed when bilirubin decreases to <3 x ULN or hepatic aminotransferases decrease to <2.5 x ULN. Please refer to summary of product characteristics for detailed guidance on dose modification s due to toxicity (including plantar palmar, erythema and gastrointestinal toxicity). Brief guidance on initial dose modifications at the first appearance of toxicity is given below. Users of these guidelines should refer to the more detailed guidance contained within the Summary of Product Characteristics (SPC) which can be viewed at www.medicines.org.uk. This includes details on how to manage 2nd and subsequent appearance of toxicities. Toxicity can be managed by symptomatic treatment and/or modification of the dose (treatment interruption or dose reduction). Once the dose has been reduced it should not be increased at a later time. Dose limiting toxicities include diarrhoea, abdominal pain, nausea, stomatitis and handfoot syndrome. Toxicity Grades * Grade 1 * Grade 2 - 1st appearance - 2nd appearance - 3rd appearance - 4th appearance * Grade 3 - 1st appearance - 2nd appearance - 3rd appearance * Grade 4 - 1st appearance Dose changes within a treatment cycle Maintain dose level Dose adjustment for next cycle/dose (% of starting dose) Maintain dose level Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Discontinue treatment permanently 100% 75% 50% Not applicable Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Discontinue treatment permanently 75% 50% Not applicable Discontinue permanently OR If physician deems it to be in the patient's best interest to continue, interrupt until resolved to grade 0-1 - 2nd appearance Discontinue permanently Gemcitabine Upper GI TSSG Chair Authorisation: and Capecitabine Date: 50% Not applicable Page 2 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 42 Thames Valley INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 Plt x 109/L ≥100 <100 Neutrophils x 109/L ≥1.5 <1.5 Serum creatinine - GFR should be calculated or measured using EDTA CONCURRENT MEDICATION Patients taking phenytoin concomitantly with capecitabine should be regularly monitored for increased phenytoin plasma concentrations. Capecitabine enhances the anticoagulant effects of warfarin. Patients taking warfarin concomitantly with capecitabine must have regular monitoring of INR. ANTIEMETIC POLICY Low emetogenic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds Diarrhoea – see dose modifications treat with loperamide or codeine Mucositis – see dose modifications Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease, arrhythmias or angina pectoris or those who develop chest pain during treatment with capecitabine. References 1. Gemcap trial arm 2 Gemcitabine Upper GI TSSG Chair Authorisation: and Capecitabine Date: Page 3 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 43 Thames Valley FLUOROURACIL continuous with radiotherapy Indication: Pancreatic cancer DRUG REGIMEN Day 1 FLUOROURACIL 225mg/m2/24 hours continuous infusion for 7 days Cycle Frequency: repeat Fluorouracil day 8, 15, 22 and 29 and so it is given continuously for 5 weeks during radiotherapy DOSE MODIFICATIONS Symptoms including diarrhoea, mucositis and leucopenia, discuss with Registrar or Consultant. Fluorouracil: Consider dose reduction in severe renal impairment only. Bilirubin <85micromol/L or ALT/AST <180 give 100% dose Bilirubin >85micromol/L or ALT/AST >180 omit The 5FU course should be delayed for a week or until completely recovered in the event of either low blood counts (neutrophils <1.5x109 or platelets <100x109) or any persistent mucositis or diarrhoea. Non-haematological toxicity (diarrhoea, stomatitis) CTC Grade 0-1 2 3 4 Haematological toxicity: 0-2 (P=or>50 & N=or>1.0) 100% 80% 50% No further treatment NFT Platelets (P), 3 (P=25-49 or N=0.5-0.9) 80% 70% 50% NFT Neutrophils (N) 4 (P<25 or N<0.5) 50% 50% 50% NFT INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 9 Plt x 10 /L ≥100 <100 ≥1.5 <1.5 Neutrophils x 109/L 2) Non-urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION ANTI-EMETIC POLICY Low emetogenic risk 5FU pancreas Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 44 Thames Valley ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds Mucositis – use routine mouthcare. Discuss dose reduction if severe. Diarrhoea – treat with codeine or loperamide. Discuss dose reduction if severe. Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease, arrhythmias or angina pectoris or those who develop chest pain during treatment with fluorouracil. 5FU pancreas Upper GI TSSG Chair Authorisation: Date: Page 2 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 45 Thames Valley FOLFIRINOX Indication: Advanced pancreatic cancer DRUG REGIMEN Day 1 ATROPINE 250mcg subcutaneously, premedication 30 minutes prior to treatment IRINOTECAN 180mg/m2 infusion in 250ml glucose 5% IV over 30 minutes Flush with glucose 5% after infusion CALCIUM LEVOFOLINATE* 175mg in glucose 5% infusion over 2 hours concurrently with oxaliplatin via a Y site placed immediately before the injection site. OXALIPLATIN 85mg/m2 in 500ml glucose 5% infusion over 2 hours FLUOROURACIL 400mg/m2 IV bolus FLUOROURACIL 2400mg/m2 continuous infusion over 46 hours via an infusor Cycle Frequency: Every 14 days for 6 cycles (review after 8 weeks) NBCalcium levofolinate is not the same as calcium folinate (calcium leucovorin). Calcium levofolinate is a single isomer of folinic acid and the dose is generally half that of calcium folinate. If calcium levofolinate is not available calcium folinate (leucovorin) may be used instead. DOSE MODIFICATIONS Symptoms including diarrhoea, mucositis and leucopenia, discuss with Registrar or Consultant. If neutrophils<1.5x109/L or platelets<100x109/L delay 1 week, only treat when neutrophils and platelets are above these limits. If >1 delay or 1 delay >or= 2 weeks reduce all the 5FU doses to 80% for future cycles. A further dose reduction may be made at the Clinician’s discretion. Fluorouracil: Consider dose reduction in severe renal impairment only. Bilirubin <85micromol/L or ALT/AST <180 give 100% dose Bilirubin > 85micromol/L or ALT/AST >180 omit Oxaliplatin: If persistent peripheral sensory symptoms occur, withdraw treatment GFR >20ml/min give 100% dose and adjust according to toxicity GFR <20ml/min dose reduce Hepatic impairment: Probably no dose reduction necessary Clinical decision f patients develop acute laryngopharyngeal dysaesthesia infuse the next cycle over 6 hours. If symptoms persist reduce dose to 65mg/m2 FOLFIRINOX Colorectal TSSG Chair Authorisation: Date: Page 1 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 46 Thames Valley Irinotecan: If Bilirubin 25 - 50micromol/L give 50% dose Bilirubin >51 clinical decision If patients suffer from severe diarrhoea, which required IV rehydration or neutropenic fever, consider reduction in subsequent cycles, discuss with SpR or Consultant. INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 Plt x 109/L ≥75 <75 Neutrophils x 109/L ≥1.5 <1.5 Serum creatinine - GFR should be calculated or measured using EDTA 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Patients who experience delayed diarrhoea will require loperamide 2mg every 2 hours to continue for 12 hours after the last loose stool. This high dose should be discontinued after 48 hours ANTIEMETIC POLICY Moderately emetogenic day 1 Low emetogenic risk day 2 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds Diarrhoea – treat with loperamide or codeine Drink large volumes of fluid containing electrolytes and an appropriate antidiarrhoeal therapy e.g. loperamide 4mg initially then 2mg every 2 hours, continuing for 12 hours after the last liquid stool (maximum of 48 hours in total). Peripheral sensory neuropathy and laryngeal spasm – avoid cold drinks and touching cold items. Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease or those who develop chest pain during treatment with fluorouracil. Mucositis – use routine mouth care FOLFIRINOX Colorectal TSSG Chair Authorisation: Date: Page 2 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 47 Thames Valley OXALIPLATIN and CAPECITABINE 21 day Indication: 2nd line advanced pancreatic cancer Unknown primary if appropriate Ensure funding is available prior to prescribing. DRUG REGIMEN Day 1 OXALIPLATIN 130mg/m2 in 500ml glucose 5% infusion over 2 hours Flush with glucose 5% after infusion CAPECITABINE 1000mg/m2 twice daily (2000mg/m2/day) po for 14 days followed by a 7 day rest Cycle frequency: Every 21 days [1] for 8 cycles Note: Tablets are only available as 150mg and 500mg tablets therefore dose must be rounded appropriately Oxaliplatin should always be administered before fluoropyrimidines. DOSE MODIFICATIONS Previous neutropenic sepsis, discuss with SpR or Consultant Symptoms including diarrhoea, mucositis and leucopenia, discuss with SpR or Consultant. Capecitabine: Check CrCl prior to every cycle CrCl (ml/min) > 50 give 100% CrCl (min/min) 30 - 50 give 75% dose CrCl (ml/min) < 30 capecitabine is contraindicated (2) Hepatic impairment – SPC recommends interruption of capecitabine therapy if treatment related elevations in bilirubin of > 3 x ULN or ALT/AST > 2.5 x ULN occur. Treatment may be resumed when bilirubin decreases to < 3 x ULN or hepatic aminotransferases decrease to < 2.5 x ULN. Please refer to summary of product characteristics for detailed guidance on dose modification due to toxicity (including plantar palmar, erythema and gastrointestinal toxicity). Brief guidance on initial dose modifications at the first appearance of toxicity is given below. Users of these guidelines should also refer to the more detailed guidance contained within the Summary of Product Characteristics (SPC) which can be viewed at www.medicines.org.uk. This includes details on how to manage 2nd and subsequent appearance of toxicities. Toxicity can be managed by symptomatic treatment and/or modification of the dose (treatment interruption or dose reduction).Once the dose has been reduced it should not be increased at a later time. Dose limiting toxicities include diarrhoea, abdominal pain, nausea, stomatitis and handfoot syndrome. Oxaliplatin + Upper GI TSSG Chair Authorisation: capecitabine Date: Page 1 of 3 Published: June 2013 Version 3.4 Review: June 2015June 2015 Regimens – Upper GI Cancer 48 Chemotherapy Thames Valley Toxicity Grades * Grade 1 * Grade 2 - 1st appearance - 2nd appearance - 3rd appearance - 4th appearance * Grade 3 - 1st appearance - 2nd appearance - 3rd appearance * Grade 4 - 1st appearance Dose changes within a treatment cycle Maintain dose level Dose adjustment for next cycle/dose (% of starting dose) Maintain dose level Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Discontinue treatment permanently 100% 75% 50% Not applicable Interrupt until resolved to grade 0-1 Interrupt until resolved to grade 0-1 Discontinue treatment permanently 75% 50% Not applicable Discontinue permanently OR If physician deems it to be in the patient's best interest to continue, interrupt until resolved to grade 0-1 - 2nd appearance Discontinue permanently 50% Not applicable Oxaliplatin: If persistent sensory symptoms occur, withdraw treatment GFR >20ml/min give 100% dose and adjust according to toxicity Omit if GFR <20ml/min [4] dose reduce Hepatic impairment: Probably no dose reduction necessary Clinical decision If patients develop acute laryngopharyngeal dysaesthesia infuse the next cycle over 6 hours. If symptoms persist reduce dose by 20%. INVESTIGATIONS Routine Blood tests 1. Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 9 Plt x 10 /L ≥75 <75 <1.5 Neutrophils x 109/L ≥1.5 2. GFR assessed using 51Cr-EDTA result or calculated creatinine clearance the Consultant’s discretion. 3. LFTs Non-urgent Blood tests Tests relating to disease response/progression. Oxaliplatin + Upper GI TSSG Chair Authorisation: capecitabine Date: Page 2 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 49 Thames Valley CONCURRENT MEDICATIONS Patients taking phenytoin concomitantly with capecitabine should be regularly monitored for increased phenytoin plasma concentrations. Capecitabine enhances the anticoagulant effects of warfarin. Patients taking warfarin concomitantly with capecitabine must have regular monitoring of INR. ANTI-EMETIC POLICY Moderately emetogenic day 1 Low emetogenic risk all other days ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds. Diarrhoea – treat with loperamide or codeine Peripheral sensory neuropathy and laryngeal spasm – avoid cold drinks and touching cold items Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease or those who develop chest pain during treatment with capecitabine. REFERENCES 1. Twelves C Oncology 2002; 16:23-26 2. Capecitabine SPC 03/2005. www.medicines.org.uk 3. Oxaliplatin SPC 09/2004 www.medicines.org.uk Oxaliplatin + Upper GITSSG Chair Authorisation: capecitabine Date: Page 3 of 3 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 50 Thames Valley CISPLATIN + MODIFIED DE GRAMONT infusor Indication: Locally advanced or metastatic carcinoma of the gallbladder DRUG REGIMEN Prehydration CISPLATIN 80mg/m2 in 1000ml sodium chloride 0.9% infusion over 4 hours CALCIUM LEVOFOLINATE 175mg in 250ml glucose 5% over 2 hours FLUOROURACIL 400mg/m2 IV bolus Post hydration FLUOROURACIL 2400mg/m2 continuous infusion over 46 hours via an infusor Day 15 CALCIUM LEVOFOLINATE 175mg in 250ml glucose 5% over 2 hours FLUOROURACIL 400mg/m2 IV bolus FLUOROURACIL 2800mg/m2 continuous infusion over 46 hours via an infusor Day 1 Cycle Frequency: Every 28 days for 3 cycles NB*Calcium folinate (calcium leucovorin) is not the same as Calcium levofolinate. Calcium levofolinate is a single isomer of folinic acid and the dose is generally half that of Calcium folinate. DOSE MODIFICATIONS Previous neutropenic sepsis, discuss with Registrar or Consultant Symptoms including diarrhoea, mucositis and leucopenia, discuss with Registrar or Consultant. Fluorouracil: Consider dose reduction in severe renal impairment only. Bilirubin <85micromol/Lor ALT/AST <180 give 100% dose Bilirubin > 85micromol/L or ALT/AST >180 omit If neutrophils<1.5x109/L or platelets<100x109/L delay 1 week, only treat when neutrophils and platelets are above these limits. If >1 delay or 1 delay >= 2 weeks reduce all the 5FU doses to 80% for future cycles. A further dose reduction may be made at the Clinician’s discretion. Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min consider carboplatin or switch to an appropriate oxaliplatin containing regimen Discuss with Consultant re omission / substitution If patient complains of tinnitus, tingling of fingers and/or toes discuss with SpR or Consultant before administration Cisplatin Mod de Gram infusor Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 51 Thames Valley INVESTIGATIONS 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 Plt x 109/L ≥100 <100 ≥1.5 <1.5 Neutrophils x 109/L Serum creatinine - GFR should be calculated or measured using EDTA 2) Non-urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN protocols. If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 20 - 40mg Furosemide PO/IV OR 200ml Mannitol 10% IV ANTI-EMETIC POLICY Highly emetogenic day 1 Low emetogenic risk days 2, 15 and 16 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Palmar plantar (hand foot syndrome) causing red palms and soles – treat with pyridoxine 50mg tds Mucositis – use routine mouthcare Diarrhoea – treat with codeine or loperamide Nephrotoxicity – ensure adequate pre and post hydration is prescribed Cardiotoxicity - special attention is advisable in treating patients with a history of heart disease, arrhythmias or angina pectoris or those who develop chest pain during treatment with fluorouracil. Cisplatin Mod Gram infusor Upper GI TSSG Chair Authorisation: Date: Page 2 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 52 Thames Valley EPIRUBICIN Indication: Locally advanced or metastatic carcinoma of the gallbladder DRUG REGIMEN Day 1 EPIRUBICIN 50mg/m2 IV bolus Cycle Frequency: Every 21 days for 6 cycles DOSE MODIFICATIONS Previous neutropenic sepsis, discuss with Consultant or Registrar. Epirubicin: Bilirubin 24-51micromol/L give 50% dose Bilirubin 51-85micromol/L give 25% dose Bilirubin >85 micromol/L omit Dose reduce in severe renal impairment.[1,2] Neutropenic Fever / Infections If Neutrophils <1, subsequent give 75% dose epirubicin If Neutrophils <0.5, subsequent give 50% dose epirubicin Maximum cumulative lifetime dose = 1000mg/m2 (in normal cardiac function) = 650mg/m2 (in combination with thoracic radiation treatment or previous anthracyclines or patients with cardiac risk factors or age above 70.) [2] INVESTIGATIONS Routine Blood tests 1. Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 ≥100 <100 Plt x 109/L <1.5 Neutrophils x 109/L ≥1.5 51 2. GFR assessed using Cr-EDTA result or calculated creatinine clearance at the Consultant’s discretion. (cisplatin) 3. LFT’s Non-urgent Blood tests Tests relating to disease response/progression. CONCURRENT MEDICATION Epirubicin Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 53 Thames Valley ANTI-EMETIC POLICY Moderately emetogenic ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Cardiotoxicity – monitor cardiac function. Epirubicin may be stopped in future cycles if signs of cardiotoxicity e.g. cardiac arrhythmias, pericardial effusion, tachycardia with fatigue. Epirubicin may be stopped in future cycles if signs of cardiotoxicity e.g. cardiac arrhythmias, pericardial effusion, tachycardia with fatigue. REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxic in hepatic impairment. 2009, The North London Cancer Network. 2. COIN guidelines. Clin Oncol (R Coll Radiol), 2001. 13: p. S211-248. Epirubicin Upper GI TSSG Chair Authorisation: Date: Page 2 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 54 Thames Valley GEMCITABINE (1000) and CISPLATIN (25) Indication: Advanced cholangiocarcinoma and gallbladder Unknown primary if appropriate DRUG REGIMEN Day 1 Prehydration CISPLATIN 25mg/m2 IV in 500ml sodium chloride 0.9% IV over 1 hour Post hydration GEMCITABINE 1000mg/m2 in 250ml sodium chloride 0.9% infusion over 30 minutes Day 8 Prehydration CISPLATIN 25mg/m2 IV in 500ml sodium chloride 0.9% IV over 1 hour Post hydration GEMCITABINE 1000mg/m2 in 250ml sodium chloride 0.9% infusion over 30 minutes Cycle Frequency: Every 21 days for 6 cycles (restage after 3 cycles) DOSE MODIFICATIONS Gemcitabine: Do not give with concurrent radiotherapy. If patient has a serum creatinine > 150micromol/L or CrCl <30ml/min consider dose reduction (Clinical decision). If bilirubin >27micromol/L initiate treatment with dose of 800mg/m2. Neutrophils >1.5x109/L and platelets >100x109/L give 100% dose Neutrophils 0.5-1.5x109/L or platelets 50-100x109/L give 75% dose or delay based on clinical assessment Neutrophils <0.5x109/L or platelets <50x109/L delay treatment (Day 1) or omit treatment (Day 8) and give 75% dose for subsequent cycles once count has recovered Diarrhoea and/or mucositis Grade 2 toxicity – omit until toxicity resolved then restart at 100% dose Grade 3 toxicity – omit until toxicity resolved then restart at 75% dose Grade 4 toxicity – omit until toxicity resolved then restart at 50% dose Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min consider carboplatin or switch to an appropriate oxaliplatin containing regimen Discuss with Consultant re omission / substitution If patient complains of tinnitus, tingling of fingers and/or toes discuss with SpR or Consultant before administration Gemcitabine and Cisplatin Upper GI TSSG Chair Authorisation: Date: Page 1 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 55 Thames Valley INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration Give Discuss Hb x g/dL ≥10 <10 Plt x 109/L ≥100 <100 Neutrophils x 109/L ≥1.5 <1.5 If Neutrophils x 109/L = 0.5-1 and or Platelets x 109/L = 50-99 give 75% dose gemcitabine and full dose cisplatin If Neutrophils x 109/L <0.5 and or Platelets x 109/L <50 delay both drugs Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion (Cisplatin) Liver function tests 2) Non-urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre-and post-hydration prescribed as per day case schedule at the end of the TVCN protocols. If urine output is < 100ml/hour or if patient gains >2kg weight during IV administration post Cisplatin give 20 - 40mg Furosemide PO/IV OR 200ml Mannitol 10% IV. ANTIEMETIC POLICY High emetogenic risk day 1 and 8 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Diarrhoea - see dose modifications Mucositis - see dose modifications Nephrotoxicity - ensure adequate pre and post hydration is prescribed. Ototoxicity - assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic impairment. 2009, The North London Cancer Network 2. J.W Valle et al; 2009 ASCO meeting Abstract 4503; J Clin Oncol 27:15s 2009(suppl;abstr 4503) 3. J.W Valle et al; ABC-02 trial; NEJM 8.4.10: Vol 362:1273-81 Gemcitabine and Cisplatin Upper GI TSSG Chair Authorisation: Date: Page 2 of 2 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 56 Thames Valley Pre-hydration and post-hydration regimens Ensure adequate diuresis is obtained prior to administration and maintained during and after administration. 1. Inpatient Pre 1L sodium chloride 0.9% + 20mmol KCl + 8mmol MgSO4 infusion over 4 hours Give cisplatin in 1000ml volume over 4 hours Post 1L sodium chloride 0.9% + 20mmol KCl + 8mmol MgSO4 infusion over 4 hours 1L sodium chloride 0.9% + 20mmol KCl + 8mmol MgSO4 infusion over 4 hours NB 1L sodium chloride 0.9% + 20mmol KCl + 8mmol MgSO4 infusion over 6 hours if oral intake is inadequate 2. Day case Pre 1L sodium chloride 0.9% + 20 mmol KCl + 8mmol MgSO4 infusion over 2 hours 200ml mannitol 10% infusion over 30 minutes Give cisplatin in 1000ml volume over 2 hours Post 1L sodium chloride 0.9% + 20 mmol KCl + 8mmol MgSO4 infusion over 2 hours NB Furosemide 40mg may be added if required Hydration Upper GI TSSG Chair Authorisation: Date Page 1 of 1 Published: June 2013 Review: 2015 Version 3.4 June 2015June Chemotherapy Regimens – Upper GI Cancer 57 Thames Valley Common Toxicity Criteria Toxicity 0 1 Allergic None Transient rash, drug fever <38C (100.4F) Alopecia Normal Mild hair loss Anorexia None Blood counts Neutrophils Within normal limits Blood counts Within Haemoglobin normal limits Blood counts Within Platelets normal limits Blood counts Within White blood normal count limits Diarrhoea None (patients with colostomy) 4 Anaphylaxis Requiring IV fluids 0.5-0.9x109/l Requiring feeding tube or parenteral nutrition <0.5x109/l 10.0g/dl – normal 8.0 9.9g/dl 6.5-7.9g/dl <6.5g/dl 75x109/l - normal 50-74x109/l 10-49x109/l <10x109/l 3.0x109/l normal 2.0-2.9x109/l 1.0-1.9x109/l <1.0x109/l Mild increase in loose, watery colostomy output compared with pre-treatment Moderate increase in loose, watery colostomy output compared with pretreatment, but not interfering with normal activity Increase of 4-6 stools/day, or nocturnal stools Physiologic consequences requiring intensive care, or haemodynamic collapse Skin changes with pain, not interfering with function >2.5 – 5.0xULN Severe increase in loose, watery colostomy output compared with pre-treatment, interfering with normal activity Increase of 7-9 stools/day, or incontinence; or need for parenteral support for dehydration Skin changes with pain, interfering with function 5.0 – 20.0xULN >1.5 – 3.0xULN 3.0 – 10.0xULN >10.0XULN Moderate (decrease in performance status Severe (decrease in performance status by 2 Bedridden or disabling Loss of appetite 1.5x109/l normal None Increase of <4 stools/day over pre-treatment Hand-foot skin reaction None Hepatic – alk phos Hepatic – bilirubin Lethargy UNL Skin changes or dermatitis without pain >ULN – 2.5x ULN >ULN – 1.5x ULN Increased fatigue over baseline, but not altering None 3 Symptomatic bronchospasm requiring parenteral medication(s) with or without urticaria; allergy related oedema / angioedema - Pronounced hair loss Oral intake significantly decreased 1.0-1.4x109/l Diarrhoea (patients without colostomy) UNL 2 Urticaria, drug fever 38C (100.4F) and/or asymptomatic bronchospasm - Increase of > 10 stools/day or bloody diarrhoea or parenteral support needed >20.0XULN Chemotherapy Regimens – Upper GI Cancer 58 Thames Valley normal activities Nausea None Able to eat Neuropathy motor Normal Subjective weakness but no objective findings Neuropathy sensory Normal Loss of deep tendon reflexes or paresthesia (including tingling) but not interfering with function Pain None Mild pain not interfering with function Stomatitis / mucositis None Painless ulcers, erythema or mild soreness Vomiting None 1 episode in 24 hours by level 1) or causing difficulty performing some activities Oral intake significantly decreased Mild objective weakness interfering with function, but not interfering with activities of daily living Objective sensory loss or paresthesia (including tingling), interfering with function, but not interfering with activities of daily living Moderate pain: pain or analgesics interfering with function but not interfering with activities of daily living Painful erythema, oedema or ulcers but can eat or swallow 2-5 episodes in 24 hours levels), or loss of ability to perform some activities No significant intake, requiring IV fluids Objective weakness interfering with activities of daily living Paralysis Sensory loss of paresthesia interfering with activities of daily living Permanent sensory loss that interferes with function Severe pain: pain or analgesics severely interfering with activities of daily living Disabling Painful erythema oedema, or ulcers requiring IV hydration Severe ulceration or requires parenteral or enteral nutritional support or prophylactic intubation Requiring parenteral nutrition, or physiological consequences requiring intensive care; haemodynamic collapse 6 episodes in 24 hours, or need for IV fluids Chemotherapy Regimens – Upper GI Cancer 59
