Principles of Cancer Chemotherapy
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Direct answer
Cancer chemotherapy uses cytotoxic drugs that exploit tumour proliferation, killing the maximum number of malignant cells at acceptable cost to normal tissues. By the log-kill hypothesis of Skipper, each cycle destroys a fixed fraction of the tumour, not a fixed number of cells — hence multiple courses are essential. Chemotherapy may be curative, adjuvant, neoadjuvant or palliative depending on the tumour and stage.
What you must remember
- Cell-cycle-specific agents act in S phase (antimetabolites — methotrexate, 5-fluorouracil, cytarabine) or M phase (vincristine, vinblastine, taxanes); cell-cycle non-specific agents — alkylating drugs, platinum compounds and anthracyclines — kill at any point and suit slow-growing tumours.
- Log-kill hypothesis: a given dose kills a constant proportion of cells, so clinical remission is not cure; residual cells are cleared by repeated cycles and host defences.
- Goals of treatment: curative regimes in acute lymphoblastic leukaemia, Hodgkin lymphoma, choriocarcinoma and testicular tumours; adjuvant therapy after surgery for micrometastases (breast, colorectal cancer); neoadjuvant therapy before surgery to downstage tumours and permit limb salvage (osteosarcoma); palliative therapy in advanced disease.
- Combination principles: drugs individually active against the tumour, different mechanisms to avoid cross-resistance, and non-overlapping toxicities; classic regimens include CHOP and ABVD.
- Dose-limiting toxicities worth memorising: cyclophosphamide — haemorrhagic cystitis from acrolein, prevented by MESNA and hydration; cisplatin — nephrotoxicity, ototoxicity and severe emesis; doxorubicin — cumulative cardiotoxicity mitigated by dexrazoxane; bleomycin — pulmonary fibrosis; vincristine — peripheral neuropathy and constipation (vinblastine is myelosuppressive); methotrexate — myelosuppression and mucositis, rescued by leucovorin.
- Shared toxicities: myelosuppression with a nadir around seven to fourteen days, mucositis, alopecia, infertility and secondary leukaemia from alkylators; tumour lysis syndrome after rapid lysis of bulky disease is prevented by hydration with allopurinol or rasburicase.
- Targeted agents complement cytotoxics — imatinib against BCR-ABL1 in CML and gastrointestinal stromal tumours, trastuzumab in HER2-positive breast cancer (itself cardiotoxic) and rituximab in CD20 lymphomas.
Common confusion
Adjuvant and neoadjuvant are habitually interchanged. Adjuvant therapy follows definitive surgery, attacking micrometastatic disease invisible to the surgeon; neoadjuvant therapy precedes it, shrinking the primary to allow less mutilating operations and providing an in-vivo test of sensitivity. A second recurring mix-up is vincristine with vinblastine — vincristine is neurotoxic and sparing of marrow, vinblastine the reverse.
Exam-focused takeaway
Theory answers should classify agents by cell-cycle specificity, state the log-kill hypothesis, list the goals of therapy and combination-regimen principles, then give the drug-toxicity map. Viva examiners ask why combinations outperform single agents and what MESNA or leucovorin rescue achieves. MCQs are dominated by drug-toxicity matching, acrolein and haemorrhagic cystitis, doxorubicin cardiotoxicity and tumour lysis syndrome biochemistry.
Frequently asked questions
What is the log-kill hypothesis?
Each dose of chemotherapy kills a constant fraction of tumour cells rather than a constant number, so repeated cycles are required to approach eradication.
How does adjuvant differ from neoadjuvant chemotherapy?
Adjuvant therapy is given after surgery to eliminate residual micrometastases; neoadjuvant therapy is given before surgery to shrink the tumour and enable less radical operations.
Why is MESNA given with cyclophosphamide?
MESNA detoxifies acrolein, the urotoxic metabolite responsible for haemorrhagic cystitis, alongside vigorous hydration.
Which chemotherapeutic drug is cardiotoxic and how is this limited?
The anthracycline doxorubicin, causing cumulative dose-related cardiomyopathy; lifetime dose capping and dexrazoxane reduce the risk.
What is tumour lysis syndrome?
Massive release of potassium, phosphate and uric acid when bulky tumours lyse, causing hyperkalaemia, hypocalcaemia and acute kidney injury — prevented by hydration and allopurinol or rasburicase.