Medical Oncology: Systemic Therapy and Drug Classes
What this domain tests
Medical Oncology questions ask you to select a systemic regimen, justify it with a biomarker or trial result, and predict the toxicity or dose adjustment that follows. Expect mechanism-of-action items on drug classes, cross-class toxicity comparisons, and one or two calculation stems such as carboplatin dosing.
Core rules
- Cytotoxic classes: alkylators (cyclophosphamide, ifosfamide - hemorrhagic cystitis, mesna), platinum (cisplatin - nephro-, oto-, neurotoxicity and high emetogenicity; carboplatin - myelosuppression), antimetabolites (methotrexate - leucovorin rescue; 5-FU/capecitabine - DPD deficiency, hand–foot syndrome, coronary vasospasm), topoisomerase inhibitors (irinotecan - cholinergic diarrhea, UGT1A1), taxanes (neuropathy, hypersensitivity, premedication), anthracyclines (cumulative doxorubicin cardiotoxicity, dexrazoxane).
- Targeted agents: trastuzumab (LVEF monitoring), rituximab (infusion reaction, HBV reactivation), TKIs (rash, diarrhea, QTc), antibody–drug conjugates (trastuzumab deruxtecan - interstitial lung disease; T-DM1 - thrombocytopenia).
- Checkpoint inhibitors: PD-L1 as predictive biomarker and immune-related adverse events in skin, gut, thyroid, lung, liver and pituitary. Grade 3–4 events mean holding drug and high-dose corticosteroids; infliximab for steroid-refractory colitis.
- Endocrine agents: tamoxifen (VTE, endometrial cancer), aromatase inhibitors (bone loss, arthralgia), GnRH agonists (tumor flare - add antiandrogen in prostate cancer), abiraterone (mineralocorticoid effects, requires prednisone).
Worked example
A 62-year-old with lung adenocarcinoma, eGFR 45 mL/min, is prescribed carboplatin AUC 5 with pemetrexed. Calvert: dose (mg) = AUC × (GFR + 25) = 5 × (45 + 25) = 350 mg. The same patient given cisplatin instead would need a creatinine clearance above about 60 mL/min plus aggressive saline hydration; with eGFR 45, carboplatin substitution is the correct answer.
Traps
- Using Cockcroft–Gault creatinine clearance when the Calvert formula calls for GFR, and forgetting to cap GFR at 125 mL/min in obesity.
- Mis-timing leucovorin rescue for high-dose methotrexate (start within 24–36 hours, continue until the level is safe).
- Missing that immunotherapy toxicity can appear weeks after the last dose, and that rechallenge after grade 3 toxicity is usually contraindicated.
- Naming a regimen whose biomarker gate has not been tested - always state the test before the drug.
- Forgetting dose reductions for hepatic dysfunction with taxanes and vinca alkaloids, and for renal impairment with methotrexate and cisplatin.