Principles of cancer chemotherapy
How cytotoxic drugs exploit cell division, why they are given in combinations and cycles, and why they share toxicities in fast-growing normal tissues.
Cytotoxic chemotherapy kills or stops the growth of cells that divide quickly. Cancer cells are the target, but bone marrow, gut lining and hair follicles also divide fast, so they are hurt too. Regimens are designed to kill as many tumour cells as possible while giving normal tissues time to recover between cycles.
The cell cycle and phase specificity
Tumours with many dividing cells (leukaemias, lymphomas, germ-cell tumours) respond better to phase-specific drugs than slow-growing solid tumours.
- G1 → S (DNA synthesis) → G2 → M (mitosis); resting cells sit in G0 and are relatively resistant
- S phase: methotrexate, fluorouracil and other antimetabolites
- M phase: vincristine and vinblastine (stop microtubule assembly), paclitaxel and docetaxel (freeze microtubules)
- G2: bleomycin; topoisomerase inhibitors (etoposide, irinotecan) act in S and G2
- Any phase: alkylating agents, cisplatin and carboplatin, doxorubicin
Fractional kill, cycles and combinations
A given dose kills roughly the same proportion of sensitive cells each time, so a tumour of many billions of cells needs repeated cycles. The gap between cycles lets marrow and gut recover. Combination regimens join drugs that act differently and do not share the same dose-limiting toxicity. Chemotherapy is often combined with surgery or radiation: before them to shrink the tumour (neoadjuvant) or after them to destroy remaining cells (adjuvant).
Shared toxicities and supportive care
- Bone marrow: neutropenia, anaemia and low platelets; colony-stimulating factors (filgrastim) shorten neutropenia
- Fever during neutropenia needs urgent assessment and antibiotics
- Nausea and vomiting: 5-HT3 antagonists, NK1 antagonists and dexamethasone
- Tumour lysis syndrome: hydration, allopurinol or rasburicase
- Drug-specific rescue or protection: calcium folinate after high-dose methotrexate, mesna for the bladder with cyclophosphamide and ifosfamide, dexrazoxane for anthracycline heart toxicity
- Organ toxicities: kidney (cisplatin), heart (doxorubicin), lung (bleomycin), nerves (vincristine, paclitaxel, oxaliplatin)
Safety in practice
Cytotoxic drugs are prepared in protected areas, double-checked and given by trained staff. Vesicants such as vincristine and doxorubicin can destroy tissue if they leak out of the vein, so the site is watched closely. Most cytotoxics harm the fetus, and contraception is discussed before treatment. Vaccinations are planned around immunosuppression (see immunopharmacology principles).
Test yourself
Think of the answer, then tap the question to see it.
Why are hair, gut lining and bone marrow affected by chemotherapy?
They contain normal cells that divide rapidly, which cytotoxic drugs also damage.
In which phase of the cell cycle do methotrexate and fluorouracil act?
S phase, when DNA is synthesised.
Why are cytotoxic drugs given in repeated cycles?
Each cycle kills a fraction of the tumour cells, so several cycles are needed, and the gaps allow normal tissues such as the marrow to recover.
Which two drugs can protect normal tissues from specific cytotoxics?
Any two of: calcium folinate (methotrexate), mesna (cyclophosphamide or ifosfamide bladder toxicity), dexrazoxane (anthracycline cardiotoxicity), amifostine (cisplatin kidney toxicity).
Example drugs
- Methotrexate
- Fluorouracil
- Vincristine
- Paclitaxel
- Cisplatin
- Doxorubicin
- Bleomycin
- Etoposide
- Irinotecan
- Calcium folinate
- Mesna
- Dexrazoxane
- Rasburicase
- Filgrastim
- Ondansetron
Connections
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Chemotherapy to Treat Cancer (National Cancer Institute (NCI), 2026); Infection and Neutropenia during Cancer Treatment (National Cancer Institute (NCI), 2026); Vincristine Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.