Systemic Anticancer Therapy (Chemotherapy, Targeted Therapy, Immunotherapy)
Core concepts
Know cytotoxic classes and mechanisms: alkylators (cyclophosphamide, cisplatin - DNA crosslinks), antimetabolites (methotrexate, 5-FU, gemcitabine - folate/pyrimidine synthesis), topoisomerase inhibitors (etoposide, irinotecan, doxorubicin), taxanes (microtubule stabilisation), vinca alkaloids (microtubule depolymerisation). Understand cell-cycle specificity vs phase-nonspecificity, log-kill and dose density, combination principles (non-overlapping toxicity, different mechanisms, synergy). Targeted agents: TKIs (imatinib, erlotinib), monoclonal antibodies (trastuzumab, rituximab, bevacizumab), ADCs (T-DM1, trastuzumab deruxtecan), CDK4/6 inhibitors, PARP inhibitors, proteasome inhibitors. Immunotherapy: checkpoint inhibitors (anti-CTLA-4, anti-PD-1/PD-L1), CAR-T, bispecifics, and immune-related adverse events (colitis, pneumonitis, thyroiditis, hypophysitis). Recognise pharmacokinetics (CYP interactions, renal/hepatic dose adjustment) and resistance mechanisms (efflux, target mutation, bypass signalling).
Traps
Questions test which toxicity belongs to which drug (anthracycline cardiomyopathy, bleomycin pulmonary fibrosis, cisplatin nephro/ototoxicity, oxaliplatin neuropathy, irinotecan diarrhoea, taxane neuropathy). Distinguish on-target vs off-target toxicity. Do not confuse predictive (HER2 for trastuzumab) with prognostic markers. Watch for steroid premedication requirements and infusion reactions.
Worked example / rule of thumb
A patient on ipilimumab + nivolumab develops diarrhoea: suspect immune-mediated colitis, hold immunotherapy, start high-dose corticosteroids, and consider infliximab if refractory. Rule of thumb: any new organ dysfunction on checkpoint inhibitors is irAE until proven otherwise.