Download Cisplatin- Etoposide

ASWCS Chemotherapy Handbook Jan 2005 Update
B3
Version 2007.1
Small Cell Lung Cancer Protocols
B3.1
Cisplatin-Etoposide (CE)
B3.1.1 Indication
•
First line chemotherapy for limited small cell lung cancer when concomitant
thoracic RT is planned which starts with the second cycle of chemotherapy
•
Prophylactic cranial radiation is given after completion of chemotherapy for
patients with good response
B3.1.2 Pre treatment Evaluation
•
Multi-disciplinary review and Histological confirmation
•
Investigations should include CT scan of chest, and upper abdomen, CXR
•
CT head scans and bone scans are performed in the event of symptoms
only
•
Record WHO performance status, current height, weight and surface area
•
FBC, U&Es (including Magnesium and Calcium), Serum Creatinine, LFTs,
LDH
•
Calculate creatinine clearance (refer to renal dose modification table)
•
Consider formal measurement of creatinine clearance in patients with low
surface area using either 24-hour urine collection or EDTA measurements
•
Consider auditory assessment
•
Document evaluable disease where appropriate
•
Give adequate verbal and written information for patients and relatives
concerning patient’s disease, treatment strategy and side effects/mortality
risk.
•
Obtain written consent from patient or guardian.
•
If appropriate, discuss potential risk of infertility/early menopause with
patient and relatives.
B3.1.3 Drug Regimen
Days
Drug
1
Cisplatin†
Dose
80mg/m²
Route
IV
1 and 2
100mg/m²
IV
Etoposide
Comments
IV infusion in 500ml Sodium
Chloride 0.9% over 60
minutes with pre and post
hydration †
IV infusion in 500-1000ml
Sodium Chloride 0.9% over
1 Hour ††
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ASWCS Chemotherapy Handbook Jan 2005 Update
3
†
††
Etoposide
200mg/m²
PO
Orally for 1 day only ††
Refer to ASWCS Individual Drug Guidelines for specific recommendations
when administering Cisplatin (Section A3.2)
In patients with swallowing difficulties, Day 3 Etoposide can be given
intravenously rather than orally (at a dose of 100mg/m2)
B3.1.4 Additional Modifications
•
None
B3.1.5 Dose Modifications
•
Dose adjustments within a cycle will be made following the guidelines
shown in the following guidelines based on weekly white blood cell (WBC),
absolute neutrophil count (ANC) and platelet counts, and clinical
assessment of non-haematological toxicity.
B3.1.5.1 Haematological
•
Defer therapy for 1 week if neutrophils<1.0 x 109/l or platelets < 100 x 109/l
Dose modifications for subsequent cycles:
•
Reduce Etoposide by 25% following symptomatic neutropenia.
B3.1.5.2 Renal Function
GFR ml/min
Cisplatin Dose
Etoposide Dose
> 55
Use AUC as per protocol – 100%
100%
46 – 54
Either / or
Substitute with Carboplatin
85%
AUC x 5
30 – 45
Cisplatin dose
80%
mg=mls/min clearance †
< 30
* Consider Dose Reduction
75%
Carboplatin Contra-Indicated if GFR
<20ml/min
†
Although there is experience of using the same dose of Cisplatin as the
Creatinine Clearance (CrCl) (i.e. 1mg/ml/min GFR, there is no evidence to support
this practice)
††
If CrCl 20-30ml/min then calculate actual GFR using EDTA clearance or
24-hour urine collection and then use calculate Carboplatin dose using Calvert
Equation with usual AUC
B3.1.5.3 Hepatic Function
Bilirubin
AST/ALT
(µmol/L)
(µmol/L)
Cisplatin
Dose
Etoposide
Dose
<26
and
Normal
100%
100%
26 – 50
and
<180
100%
50%
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ASWCS Chemotherapy Handbook Jan 2005 Update
<51
and
≥180
100%
omit / 25% *
51 – 85
and
Normal
100%
25% *
>85
and
Normal
omit / delay
omit / delay
*
The decision to treat should be confirmed by the consultant
B3.1.5.4 Other Non-Haematological Dose Modifications
•
In case of grade 3 or 4 neurotoxicity, Cisplatin should be definitively
stopped.
B3.1.6 Antiemetics/supportive therapy
•
This regimen has moderate to severe emetic potential - refer to local
protocol
•
Continuous Ciprofloxacin 250 mg bd and Fluconazole 50 mg od following
symptomatic neutropenia
•
If Mucositis or Diarrhoea ≥ Grade 3 in previous course then give 66% dose
of both agents
B3.1.7 Cycle frequency
•
21 days for up to 6 cycles
B3.1.8 Adverse effects
•
Nausea/vomiting
•
Myelosuppression and risk of sepsis and thrombocytopenia
•
Constipation and/or diarrhoea
•
Alopecia
•
Peripheral neuropathy & ototoxicity including tinnitus
•
Encephalopathy
•
Caution with extravasation due to vesicant drugs
•
Nephrotoxicity
•
Ototoxicity
•
Stomatitis & Mucositis
•
Fatigue
•
Lung fibrosis
•
Haemorrhagic cystitis
•
Line thrombus
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ASWCS Chemotherapy Handbook Jan 2005 Update
•
Electrolyte Imbalance (especially hypomagnesaemia and
hypocalcalcaemia)
•
Hypersensitivity Reactions
B3.1.9 Investigations Prior to Subsequent Cycles
•
Before each course check:
1. FBC
2. U&Es (including albumin & magnesium)
3. Serum Creatinine and consider formal measurement of creatinine
clearance in patients with low surface area using either 24-hour urine
collection or EDTA measurements. Ensure that calculated creatinine
clearance >55mls/min (refer to renal dose modification table)
4. LFTs
•
Clinical toxicity assessment (including stomatitis, neurotoxicity &
ototoxicity)
B3.1.10 References
•
Hanna N, Bunn P, Langer C, Einhorn L, Guthrie T, Beck T, Ansari R, Ellis
P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized
Phase III Trial Comparing Irinotecan/Cisplatin With Etoposide/Cisplatin in
Patients With Previously Untreated Extensive-Stage Disease Small-Cell
Lung Cancer. Journal of Clinical Oncology, 2006; 24 (13); Pg. 2038-2043
•
Fukuoka M, Furuse K, Saijo N et al. Randomised trial of
Cyclophosphamide, Doxorubicin and Vincristine versus Cisplatin and
Etoposide versus alternation of these regimens in small-cell lung cancer.
1991. J Natl. Cancer Inst. 83: 855-61
Written By: Dr S Falk, Chemotherapy Head of Service, BHOC
Authorised By:
Chairman of ASWCS
Network Pharmacist
Group
Name:
Digitally signed by
Mr
Signature: Jarrod
Dunn
Mr Jarrod Dunn
DN: CN = Mr
Jarrod Dunn, C =
GB, O = ASWCS
Date: 2007.03.23
15:14:33 Z
Chairman of ASWCS
Network Nursing Group
Name:
Tariq
Signature: White
Date:
Date:
Date for review: November 2008
Digitally signed by
Tariq White
DN: CN = Tariq
White, C = GB, O
= ASWCS
Date: 2007.03.23
15:14:46 Z
Chairman of ASWCS
Drugs & Therapeutics
Committee
Name:
Signature:
Date:
Dr Steve
Falk
Digitally signed by Dr
Steve Falk
DN: CN = Dr Steve
Falk, C = GB, O =
ASWCS
Date: 2007.03.23
15:14:56 Z
23/03/2007
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