Systemic Therapy: Chemotherapy, Targeted Agents and Immunotherapy
What this domain tests
This domain tests drug-class knowledge, dose calculation and modification, and the biomarker logic that selects targeted agents and checkpoint inhibitors. Expect questions that combine a creatinine value, a molecular result and a toxicity grade.
Core rules
- Cytotoxic classes: alkylating agents (cyclophosphamide, ifosfamide), platinum compounds, antimetabolites (5-FU, capecitabine, gemcitabine, pemetrexed, methotrexate), topoisomerase I inhibitors (irinotecan, topotecan), topoisomerase II inhibitors (etoposide), taxanes, anthracyclines, vinca alkaloids.
- Dose calculation: most cytotoxics use body surface area; carboplatin uses the Calvert formula, total dose (mg) = target AUC × (GFR + 25). Verify renal function for cisplatin (creatinine clearance), and reduce or omit for capecitabine, methotrexate and pemetrexed in renal impairment.
- Cumulative limits: doxorubicin 550 mg/m² (400 mg/m² with mediastinal radiotherapy); bleomycin pulmonary toxicity rises above roughly 400 units.
- Targeted agents need a target: EGFR and ALK rearrangements in lung cancer, HER2 amplification, KRAS G12C, BRCA1/2 for PARP inhibitors, ER and HER2 for endocrine and anti-HER2 therapy, MSI-H/dMMR and high TMB for immunotherapy.
- Immune-related adverse events (colitis, hepatitis, pneumonitis, thyroiditis, hypophysitis, myocarditis) are managed by grade: hold for grade 2, corticosteroids for grade 2–3, permanent discontinuation for grade 4 (except endocrinopathies managed by replacement).
- Extravasation: stop the infusion, aspirate residual drug, and use dexrazoxane for anthracyclines or hyaluronidase for vinca alkaloids.
Worked example
A patient with a GFR of 60 mL/min is prescribed carboplatin at AUC 5. Dose = 5 × (60 + 25) = 425 mg intravenously every 3 weeks. Reasoning: the Calvert formula substitutes measured or calculated GFR directly and adds 25 to account for the agent's non-renal clearance; forgetting the +25 gives 300 mg and systematic underdosing.
Traps
Capping BSA at 2.0 m² without institutional policy; giving live vaccines during cytotoxic therapy; continuing immunotherapy after a grade 3 colitis; missing pre-treatment DPYD testing before fluoropyrimidines.