PH8.11 | PH8.11 | Anticancer Drugs and Toxicity Amelioration — SDL Guide — Summary & Reflection

KEY TAKEAWAYS

Cell-cycle specificity: CCNS (alkylators, anthracyclines — kill in any phase including G0); CCS (antimetabolites — S; vinca alkaloids — M; taxanes — M by opposite mechanism; bleomycin/etoposide — G2/M).

Alkylating agents: Covalent DNA crosslinks. Cyclophosphamide → acrolein → haemorrhagic cystitis → MESNA + hydration. Cisplatin → nephrotoxicity → IV hydration + amifostine; ototoxicity (irreversible); severe CINV.

Antimetabolites: S-phase. Methotrexate (DHFR inhibitor) → mucositis/bone marrow → leucovorin rescue (after HD-MTX). 5-FU (TS inhibitor) + leucovorin = enhanced TS inhibition (leucovorin modulates 5-FU efficacy, different from MTX rescue). 6-MP + allopurinol → reduce 6-MP to 25% (XO inhibition → accumulation).

Vinca alkaloids: Inhibit tubulin polymerisation → M-phase arrest. Vincristine: non-myelosuppressive; neuropathy + constipation (prophylactic laxatives). Vinblastine: myelosuppressive.

Taxanes: Stabilise microtubules (OPPOSITE to vincas) → M-phase arrest. Paclitaxel: Cremophor → hypersensitivity (premedicate). Bleomycin: DNA strand scission via free radicals; pulmonary fibrosis (DLCO monitoring; avoid high FiO₂ perioperatively).

Doxorubicin: DNA intercalation + TopII + free radicals; cumulative cardiomyopathy (>450 mg/m²) → dexrazoxane + echo monitoring. Vesicant — never extravasate.

CINV: Cisplatin (most emetogenic) → ondansetron + aprepitant + dexamethasone triple therapy. Tumour lysis: rasburicase (check G6PD first) or allopurinol + hydration.

REFLECT

A 30-year-old man with a curable Hodgkin lymphoma is too frightened to start ABVD chemotherapy after reading about hair loss, nausea, and heart damage online. He asks: 'Is it worth going through all this?' Consider the pharmacological reality: doxorubicin in ABVD is given at doses (total cumulative ~200 mg/m² for a standard 6-cycle regimen) well below the cardiomyopathy threshold (450–550 mg/m²); bleomycin lung toxicity is monitored with PFTs; CINV is manageable with modern anti-emetics; alopecia is reversible. Hodgkin lymphoma has a cure rate exceeding 85% with ABVD chemotherapy. How would you use your pharmacological understanding of toxicity management — not to minimise the patient's fears, but to make them specific, quantifiable, and manageable — to help this patient make an informed decision?