Examqo › Examqo library › Oncology › Principles of systemic therapy · IMLE
Chemotherapy pharmacology — mechanisms, the cell cycle and pharmacokinetics
Each chemotherapy damages DNA or cell division at a different point — alkylation, platinum, antimetabolites, topoisomerase inhibitors and microtubule drugs; exposure is measured as AUC, and carboplatin dosing is set by AUC and kidney function.
Why it matters in the exam
Pharmacology questions in the bank test understanding of mechanism and kinetics: what the AUC shows, how to calculate a carboplatin dose, the role of leucovorin with 5-FU, what causes resistance to pemetrexed, and when to switch cisplatin to carboplatin. The questions look theoretical, but each one links to an everyday treatment decision.
Another recurring topic is pharmacogenetics — DPD deficiency before 5-FU and capecitabine, and UGT1A1 before irinotecan — as well as differences between formulations, such as the advantages of nab-paclitaxel over standard paclitaxel. It is also worth remembering which drugs need adjustment for kidney function and which for liver function.
Key points
- Each chemotherapy group hits a different point: alkylation, platinum cross-links, base mimicry, DNA cutting through topoisomerase, or microtubules.
- AUC expresses total drug exposure, and the carboplatin dose is set by a target AUC and GFR in the Calvert formula.
- Leucovorin enhances the action of 5-FU on thymidylate synthase, and resistance to pemetrexed is linked to increased expression of the enzyme.
- Before 5-FU check DPD and before irinotecan think of UGT1A1, because deficiency causes severe toxicity.
- Cisplatin is switched to carboplatin when creatinine clearance is below 60, or with hearing loss, neuropathy or heart failure.
Summary table
| Group | Mechanism and cycle phase | Examples and details |
|---|---|---|
| Alkylators | Binding alkyl groups to DNA and cross-linking; not phase-dependent | Cyclophosphamide, ifosfamide, temozolomide; risk of MDS and AML years later |
| Platinum | Intrastrand and interstrand DNA cross-links | Carboplatin dosed by AUC: dose in mg = target AUC times (GFR plus 25) |
| Antimetabolites | Mimic bases or folic acid; active in S phase | 5-FU inhibits thymidylate synthase, and leucovorin stabilises the binding; pemetrexed inhibits several folate pathway enzymes |
| Topoisomerase inhibitors | Topo I: irinotecan, topotecan; topo II: etoposide and anthracyclines | Topo II inhibitors are linked to relatively rapid secondary leukaemia |
| Microtubule drugs | Taxanes stabilise microtubules; vinca alkaloids and eribulin prevent polymerisation; M phase | nab-paclitaxel: no oil-based solvent, no steroid premedication needed and a shorter infusion |
| Pharmacokinetics | AUC = total drug exposure over time | DPD deficiency (5-FU) and UGT1A1 (irinotecan) increase exposure and toxicity |
| Switching cisplatin to carboplatin | Creatinine clearance below 60, hearing loss, neuropathy, heart failure or poor performance status | Resistance to pemetrexed: increased thymidylate synthase expression |
In the full version for subscribers
- A simple algorithm
- Memory aid
- Exam traps
- 5 review cards
- Enough for IMLE
The full version is open to subscribers of: Oncology, Internal medicine, Medical licensing exam (IMLE).
Subscriber? Read the full topic Plans and prices 25 free questions
Sources
- Chabner and Longo, Cancer Chemotherapy, Immunotherapy and Biotherapy: Principles and Practice, 6th ed. (2018) — Clinical pharmacology of antineoplastic agents
- DeVita, Hellman and Rosenberg's Cancer: Principles and Practice of Oncology, 12th ed. (2023) — Pharmacokinetics and pharmacodynamics of anticancer drugs
- Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (2023) — Cytotoxic drugs
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-06. The text may contain errors; when in doubt, check the source.