Basic considerations of chemotherapy

this is sort of chemotherapy for beginers.... part 1

1. Basic considerations of chemotherapy Dr. R ajib Bhattacharjee Consultant Dept. of Medical Oncology CNCI

2. WHAT IS CHEMOTHERAPY?

3. WHY DO WE NEED MULTIPLE CYCLES OF CHEMOTHERAPY

4. WHY 21 DAY CYCLE? GOMPERTZ CURVE

5. WHO CAN BE TREATED? PS 0-2 Consider Chemo PS 3-4 Do not consider Chemo

6. ALKYLATING AGENTS

7. CYCLOPHOSPHAMIDE Forms- Tab & Inj Drug interaction – doxo + cyclo = increased cardiotoxicity Renal compromise – use with caution. CrCl may be calculated before chemo. Toxicities Myelosuppression – calculate ANC Bladder toxicity – hydration, MESNa Moderate to high emetogenic

8. IFOSFAMIDE Forms – only Inj (oral form is highly neurotoxic ) Drug interaction – Enzyme inducers lead to increased activation to active substrate Cisplatin – increased Ifosfamide induced renal toxicity Warfarin – closely monitor PT, INR

9. IFOSFAMIDE Administration Prophylactic antiemetic Uroprotection – hydration, MESNa , start early Renal compromise – use with caution. CrCl may be calculated before chemo. Monitor urine RE before each cycle

10. IFOSFAMIDE Toxicities Myelosuppression Bladder toxicity – hemorrhagic cystitis, chronic fibrosis, secondary cancers Nausea and vomiting Neurotoxicity

11. MESNa Form – tab or inj Used to protect bladder from hemorrhagic cystitis caused by Ifosfamide or Cyclophosphamide Dose – std dose Ifosfamide – 60% of Ifos dose high dose ifosfamide – 100% of Ifos dose Timing of dose – 0, 4, 8 Hrs after starting Ifosfamide

12. DACARBAZINE Form – Injectable Metabolized in liver Highly emetogenic Toxicities Myelosuppression Flu like syndrome – last for several days Neuropathy Photosensitivity – avoid sun exposure

13. BENDAMUSTINE Use with caution in patients with mild or moderate renal impairment. Bendamustine should not be used in patients with CrCl < 40 mL /min. Use with caution in patients with mild hepatic impairment. Monitor for tumor lysis syndrome, especially within the first treatment cycle. Closely monitor CBCs on a periodic basis. Bendamustine therapy should be held or discontinued in severe or progressive skin reactions

14. PLATIN COMPOUNDS

15. CISPLATIN Form – injectable Cisplatin should be used after other chemo drugs Should be used with caution in renal compromise Check electrolytes (Na, K, Ca, Mg) during T/t Aggressive hydration before and after Cisplatin Highly emetogenic – aggressively control nausea vomiting Caution in patient with pre-existing hearing difficulty

16. CISPLATIN Toxicities Nephrotoxicity – electrolyte abnormality Nausea and vomiting – acute & delayed Myelosupression Ototoxicity Neurotoxicity Transient elevation in liver enzymes

17. CARBOPLATIN Form – injectables Cockroft Gault Formula

18. CARBOPLATIN Caution in renal compromised patients Oral hydration is adequate Toxicities Myelosuppression – much more than Cisplatin Neuropathy – much less than Oxaliplatin Nephrotoxicity – much less than Cisplatin Nausea & Vomiting - much less than Cisplatin

19. OXALIPLATIN Form – injectables Caution in renal compromised patients Neurotoxicity

20. OXALIPLATIN Oxaliplatin should be mixed in 5%D only. It should not come in contact with NS Toxicity Neurotoxicity – peripheral sensory neuropathy dyesthesia in laryngopharynx Nausea & vomiting Myelosupression Hepatotoxicity

21. Dose limiting toxicities of Platins

22. TOPOISOMERASE INHIBITOR

23. ETOPOSIDE Forms- Tab & Injectables Hepatic metabolism – caution in abnormal LFT Caution in renal compromise Hypotension - stop infusion and start IV fluids after BP correction restart at lower rate

24. ETOPOSIDE Toxicities Myelosuppression Nausea vomiting Mucositis , diarrhoea Hypersensitivity reaction Alopecia Metallic taste during drug infusion

25. IRINOTECAN Form – inj Emetogenic drug – anti-emetics needed Mildly vesicant drug – be careful about extravasation Be extra cautious in elderly patients(>65yrs), poor PS patients, and patients who have received prior abdominal or pelvic radiation Ask patients to avoid laxatives

26. IRINOTECAN EARLY DIARRHOEA Within 24 hrs of administration Cholinergic effect Treated with Atropine (0.25-1mg) Prophylaxis indicated if previous history LATE DIARRHOEA Direct gastric irritation Treated with Loperamide Oral Fluoroquinolone IV Antibiotics & IV fluids

27. IRINOTECAN Toxicities Diarrhoea Myelosuppression Nausea & vomiting

28. ANTIBIOTICS

29. DOXORUBICIN Form – injectable Drug interaction – Doxo+Cyclo = Increased risk of hemorrhagic cystitis Be cautious in patients with liver dysfunction Reduce dose in renal impairment (50% dose reduction if creat is more than 5.0mg/dl) Be cautious in elderly patients

30. DOXORUBICIN Monitor cardiac function with echocardiography Cummulative dose – 450mg/m 2 Red orenge discoloration of urine Vesicant Avoid sun exposure Radiation recall phenomenon

31. DOXORUBICIN ADMINISTRATION

32. DOXORUBICIN Toxicities Myelosuppression Cardiotoxicity Acute – Conduction disturbances, chest pain, myopericarditis Chronic – Dilated cardiomyopathy CHF Mild nausea & vomiting Mucositis & Diarrhoea Alopecia Skin rash

33. EPIRUBICIN Form – injectable Drug interaction – Epi+Cyclo+5FU = Increased myelosuppressionm > prophylactic G-CSF support needed Be cautious in patients with liver dysfunction Reduce dose in renal impairment (50% dose reduction if creat is more than 5.0mg/dl) Be cautious in elderly patients

34. EPIRUBICIN Monitor cardiac function with echocardiography Cumulative dose – 900mg/m 2 Red orange discoloration of urine Avoid sun exposure

35. EPIRUBICIN Extravasation Radiation recall

36. EPIRUBICIN Toxicities Myelosuppression Cardiotoxicity Acute – Conduction disturbances, chest pain, myopericarditis Chronic – Dilated cardiomyopathy CHF Mild nausea & vomiting Mucositis & Diarrhoea Alopecia Skin rash

37. BLEOMYCIN Form – injectable Renal elimination – caution in renal compromised patients Pulmonary toxicity – check PFT, and CXR before start of treatment and every cycle. >15% decrease in PFT values warrants discontinuation of treatment Max Cummulative dose – 400 U Oxygen therapy enhance pulmonary toxicity Lymphoma patients are at increased risk of developing anaphylactic reaction

38. BLEOMYCIN

39. NEXT TIME… Anti-metabolites – Gemcitabine , 5FU, Capecitabine , Methotrexate , Pemetrexed Taxanes – Paclitaxel , Docetaxel Vinca alkaloids – Vincristine , Vinblastin Others…