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Complications of Chemotherapy • Discuss post-chemotherapy complications and their management • Chemotherapy can have wide-ranging effects on patients • Human body amazing at what it can tolerate What is chemotherapy? • Treatment with drugs that kill cancer cells (or • make them less active) Interfering with tumour cells ability to grow and proliferate – Adjuvant chemotherapy ie localized breast cancer – Induction chemotherapy ie AML – Curative chemotherapy ie Diffuse Large B Cell Lymphoma – Palliative chemotherapy Categories of Chemotherapy • • • • • • • • Antibiotic derived—anthracyclines, bleomycin Plant Alkaloids—periwinkle plant--vincristine, paclitaxel Alkylators—cylcophosphamide Antimetabolites—interfere with synthesis of nucleic acids-5FU, Methotrexate Epipodophyllotoxins—inhibit topoisomerase 2--etoposide Anti-hormonal—tamoxifen, coritcosteroids TYROSINE KINASE INHIBITORS--GLEEVEC MONOCLONAL ANTIBODIES—TARGETED therapy Complications of Chemotherapy • SHORT TERM Fever Nausea Infusional reactions Oral complications Diarrhea Anemia Neuropathy Alopecia Rash, Extravasation Emotional FEBRILE NEUTROPENIA On Chemotherapy, 7 to 14 days post chemo WBC nadir, NEUTROPHILS are 1st line of DEFENCE Temperature great than or equal to 38.3 degrees centigrade Absolute Neutrophil count (ANC) less than 1.0 One of the few Oncologic EMERGENCIES FEBRILE NEUTROPENIA • History, Physical • Focus on possible source of infection • Respiratory tract, urine, skin, gi tract • CBC, LFT,CR • CXR FEBRILE NEUTROPENIA • Draw cultures from 2 different sites, urine C/S • 50% of cultures positive – 65% positive cultures are gram positive organisms • Broad Spectrum antibiotics • If well, hemodynamically stable – CIPRO and CLAVULIN PO and home FEBRILE NEUTROPENIA • IF UNWELL • ADMIT WITH BROAD SPECTRUM IV ANTIOBIOTICS IE TAZOCIN OR IMIPENEM OR AMP AND GENT • WITH NEUPOGEN SUPPORT( 300mcg sc daily until anc >1.0), IV FLUIDS ETC. FEBRILE NEUTROPENIA • Usually fever lasts less than 48 hours • If fever longer than 48 hrs, patient needs IV antibiotics, consider antifungals • Usually bacterial or viral infections but fungal infections becoming more of an issue • As WBC and ANC recover, patient usually improves NB special situation for Acute Leukemics, PICC lines FEBRILE NEUTROPENIA • Clinical consideration and follow-up very important, especially if patient discharged home NAUSEA • Most chemotherapeutic agents cause nausea • Why? 1) systemically as drug makes it’s way to nausea centre of brain (chemotherapeutic trigger zone) 2) Sight and smell of drug Neuronal pathways involved with chemotherapy- and radiotherapy-induced nausea and vomiting Sensory input (pain, smell, sight) Chemotherapy Chemotherapy Radiotherapy Chemoreceptor Trigger Zone (area prostrema, 4th ventricle) Stomach Small intestine Higher cortical centres Memory, fear, anticipation Vomiting Centre (medulla) Vomiting Reflex Labyrinths Neuronal pathways Factors which can cause nausea & vomiting NAUSEA • Types of Nausea – Anticipatory—conditioned reflex to sight and smell of chemotherapy area – Acute—within 24hrs and related to chemotherapeutic agents – Delayed—more than 24 hrs. post chemotherapy--specific agents—cisplatin, cyclophosphamide, adriamycin NAUSEA • Worst offenders: – Cisplatin – High dose cyclophosphamide – Doxorubicin, eprirubicin, carboplatin also have a high incidence of nausea NAUSEA TREATMENT Medications: Prochlorperazine (stemetil) Metoclopramide (maxeran) Ondansetron (Zofran)—5HT3 antagonists Dexamethasone Lorazepam, Haloperidol Aprepitant Drug treatment of chemotherapy- and radiotherapy-induced nausea and vomiting Sensory input (pain, smell, sight) Higher cortical centres Histamine antagonists Muscarinic antagonists Dopamine antagonists Cannabinoids Chemotherapy Chemoreceptor Trigger Zone (area prostrema, 4th ventricle) Memory, fear, anticipation Benzodiazepines Vomiting Centre (medulla) Vomiting Reflex 5HT3 antagonists Sphincter modulators Chemotherapy Radiotherapy Stomach Small intestine Labyrinths Neuronal pathways Factors which can cause nausea & vomiting Sites of action of drugs NAUSEA TREATMENT • Relaxation • Varying foods, meals INFUSIONAL REACTIONS • Very common with new MONOCLONAL • • • • • ANTIBODY agents ie RITUXIMAB Infusion of these agents may take several hours Fever, hypotension, asthmatic like reactions, pain Premedicate or treat with Dexamthasone, Benadryl, Tylenol May have to stop infusion temporarily If serious, may have to discontinue agent Oral Complications • Occurs in approx 40% of patients receiving chemotherapy • Very common • Team approach using nutritionist, nursing, dentist, pain management team • Oral hygiene important-soft tooth brushes, floss? • Source of bacteremia Oral Complications • loss of taste – Affects appetite, nutrition – Which in turn affects healing – In this situation, we advise patients to think of eating as a job – Sometimes, oral complications require nutrition supplements or alternatives MUCOSITIS • Chemotherapy is intended to injure rapidly dividing cells such as the MUCOSA • Presents with mouth sores, inflammation, sometimes sloughing of mucosa anywhere in the GASTROINTESTINAL TRACT, RESP TRACT … • Usually occurs in the mouth MUCOSITIS • SIMPLE ORAL MUCOSITIS TREATED WITH MOUTH RINSE – MAGIC MOUTHWASH – SALT WATER GARGLES – TOPICAL ANALGESIA ie Xylocaine viscous, tantum – Systemic analgesia – NYSTATIN MUCOSITIS • Upper gi tract – Heartburn – Very common • Antacid, Ranitidine, Pantoloc MUCOSITIS • SEVERE MUCOSITIS – GI TRACT • DIARRHEA, SLOUGHING OF MUCOSA, ESOPHAGITIS • ADMISSION, TNA, BOWEL REST, OTHER SUPPORTIVE MEASURES • 5FU ONE OF THE MAIN CULPRITS DIARRHEA • VERY COMMON, approx 45%. USUALLY A FEW DAYS AND SELF-LIMITING DIARRHEA • Risk factors – Elderly – Known colitis – GI tumour – 5FU, irinotecan – Concomitant irradiation DIARRHEA • Infection—CDIFF or other • Laxatives, other medications (stool softeners) • Of course, usually the chemotherapy is the culprit. DIARRHEA • Usually self-limiting • Hydration—po, IV if more SERIOUS • Diet—fluids, BRAT (Bananas, Rice, Apples, Toast) • Loperamide (immediately if on Irinotecan) – 4mg followed by 2mg Q4H or until formed stool. Up to 16 mg per day – Usually rule out CDIFF first DIARRHEA • If severe, Ocreotide (Sandostatin) – Decreases fluid output from bowel – 100mcg sc TID – Growth hormone analogue-decreases all salivary gland secretions And Antibiotics may be considered espec if CDIFF positive oral metronidazole or oral vancomycin oral CIPRO ANEMIA • Bone marrow suppression from chemotherapeutic agents • Secondary to malignancy • Anemia work-up ANEMIA • Chemotherapy induced anemia • Erythropoietin, Aranesp – Stimulate marrow to produce RBC’s – Used while on chemotherapy only – Additional iron: po vs. iv – Sc injection ANEMIA • Adverse effects of Erythropoietin – Flu-like illness – Rashes – Diarrhea – Headache – Bone pain – Liver, kidney – Vascular event: FOLLOW HEMOGLOBIN ANEMIA • Dosage: Eprex 40,000 units sc qweekly Aranesp: 150mcg sc qweeklyto 7 days) NEUROPATHY • Very common with vincristine, vinblastine, cisplatin • Usually temporary. • Sometimes leads to dose alterations or stopping of some drugs NEUROPATHY • Most commonly, we see numbness and tingling in fingers and toes • Can you do up your buttons? • Is numbness becoming more proximal? • May need to alter chemotherapeutic agents or doses thereof Emotional effects of chemotherapy • Malignant diagnosis can be overwhelming • The discussion of treatments and adverse effects can also be overwhelming • Anxiety, depression, fatigue related to diagnosis and treatments • LOTS of information regarding treatments Emotional effects of chemotherapy • “Gaining Control by giving up control”. Dr. B. Rotella • daily routine goes upside down • Changing work routine…missing work for weeks, months • Income changes Emotional effects of chemotherapy • “The inability to forget is infinitely more devastating than the inability to remember”. Mark Twain • Hard to forget some of the stressful times one goes through • Battle fatigue Emotional effects of chemotherapy • “It always seems impossible until it’s done”. Nelson Mandela • Getting through months of chemotherapy is very, very difficult • People are amazing though. • The human condition is to battle Emotional effects of chemotherapy • “Things to do today: Exhale, Inhale, Exhale”. Buddha • Just surviving each day step by step • Team approach: social worker, supportive care coordinators, pastoral care, pharmacy Complications of Chemotherapy • Longterm – Cardiac – Secondary Malignancies – Fatigue – Neuropathy – Arthropathy Cardiac Complications • Adriamycin or other anthracyclines • 450mg per m2 dose lifetime • Strong treatment for breast cancer and hematologic malignancies • Affects myocardium longterm above maximum dose Secondary Malignancies • Skin cancers • Breast cancers • Hematologic Malignancies Fatigue • Thorough history, physical exam and ancillary tests • Fatigue workshop Arthropathy • Post monoclonal antibodies • Treated in usual fashion with NSAIDs, prednisone GLEEVEC • Oral “chemotherapy” for Chronic Myeloid • • • • Leukemia Molecular model of chemotherapeutic treatments, tyrosine kinase inhibitor Philadelphia Chromosome produces abnormal protein, BCR-ABL Gleevec stops the signal of the BCR-ABL protein, therefore halting Leukemogenesis Fluid retention, diarrhea, nausea, fatigue, abdo pain, muscle cramps, bone pain