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PH8.11 | PH8.11 | Anticancer Drugs and Toxicity Amelioration — SDL Guide — SDL Guide (Part 3)

Self-Assessment: Anticancer Pharmacotherapy

Apply your knowledge to these clinical scenarios:

Scenario A: A 55-year-old man with metastatic colon cancer receives FOLFOX (5-FU + leucovorin + oxaliplatin). After 4 cycles, he develops tingling and numbness in his hands and feet that worsens when he touches cold objects. He also complains of severe nausea after each infusion. (1) What is the cause of the tingling? (2) Is leucovorin given to this patient to rescue him from methotrexate toxicity? Explain its actual role. (3) What anti-emetic regimen do you recommend?

Discussion: (1) Oxaliplatin neuropathy — oxaliplatin causes both acute cold-triggered dysaesthesia (immediately after infusion — distinctive, pathognomonic for oxaliplatin; advise avoidance of cold drinks/food/objects for 48 hours post-infusion) and cumulative sensory peripheral neuropathy (dose-limiting). No reliably effective neuroprotective agent — dose reduction or discontinuation if severe. (2) Leucovorin in FOLFOX is NOT given to rescue from methotrexate (there is no methotrexate in FOLFOX). It is given to modulate (enhance) 5-FU activity: leucovorin stabilises the FdUMP-thymidylate synthase-leucovorin ternary inhibitory complex → prolongs TS inhibition → enhances 5-FU's anticancer effect. This is a frequently confused point — leucovorin has two distinct contexts in oncology (MTX rescue vs 5-FU modulation). (3) Oxaliplatin is moderately emetogenic; 5-FU also contributes. Recommended: ondansetron (5-HT₃ antagonist) + dexamethasone ± aprepitant (for the delayed CINV component); can add lorazepam for anticipatory nausea.

Scenario B: A 12-year-old girl with ALL (acute lymphoblastic leukaemia) is started on VDCP induction chemotherapy including vincristine. After the first dose, she develops severe constipation and reports difficulty with her grip. How do you manage and prevent these toxicities?

Discussion: Vincristine-induced autonomic and peripheral neuropathy — the constipation results from autonomic neuropathy of the bowel (reduced gut motility → paralytic ileus in severe cases). Management: (1) Prophylactic laxatives (stimulant laxative — senna or bisacodyl — from day 1 of vincristine, before constipation begins; continue throughout vincristine-containing therapy). Increased fibre and hydration. (2) For the grip weakness (motor neuropathy — rare but serious at standard paediatric doses): monitor neurologically; consider dose reduction if severe motor neuropathy develops. Importantly, vincristine dose is NOT adjusted for myelosuppression (it is not myelosuppressive) — adjustments are for neurological toxicity.

Scenario C: A 45-year-old woman with HER2-positive breast cancer is treated with AC (doxorubicin + cyclophosphamide) × 4 cycles followed by paclitaxel + trastuzumab × 4 cycles. She asks: 'Can I take both doxorubicin and Herceptin together, since both are for my cancer?' How do you counsel her?

Discussion: Concurrent doxorubicin + trastuzumab is not recommended due to synergistic cardiotoxicity — both agents cause left ventricular dysfunction by different mechanisms (doxorubicin via oxidative free radical damage; trastuzumab via HER2 signalling inhibition in cardiomyocytes, which need HER2 for survival signalling). Clinical trial data show significantly higher rates of cardiac events with concurrent use. Standard practice: complete AC (4 cycles) first, then switch to paclitaxel + trastuzumab (sequential, not concurrent). LVEF monitoring: echo before starting any anthracycline, and before starting trastuzumab. If LVEF falls >10% from baseline or to <50%, hold trastuzumab (the cardiotoxicity of trastuzumab is reversible — unlike anthracycline cardiomyopathy which is permanent at high cumulative doses).