Principles of chemotherapy

Summary

Chemotherapy is any pharmacological agent given with the intention of eradicating malignant cells, and can be given intravenously, orally and topically. It is the mainstay of treatment of germ cell tumours, lymphomas and leukaemias. It is also used with curative intent as an adjunct to surgery or radiotherapy (RTX) in many tumour types and with palliative intent in metastatic disease.

Systemic chemotherapy: definitions

Neoadjuvant: the use of chemotherapy prior to surgery or RTX to downstage tumour.

Adjuvant: the use of chemotherapy after surgery to eradicate micrometastases and improve overall survival.

Palliative: the use of chemotherapy to palliate symptoms and prolong the life of patients with metastatic disease.

Cytotoxic chemotherapy

Cytotoxic chemotherapy is relatively non-selective. It is not targeted to the tumour and damages normal cells as well as cancer cells. However, malignant cells are more sensitive to its effect because they do not have the same capacity for repair. Cytotoxic drugs predominately damage proliferating cells; malignant tumours are often rapidly growing and therefore susceptible to damage from cytotoxics. Rapidly proliferating normal tissues such as bone marrow and mucous membranes are also often affected, accounting for (some of) the common side-effects of myelosuppression and mucositis.

Cytotoxic chemotherapy drugs have a narrow therapeutic index. This means that the difference between maximum tolerated dose (MTD) and minimum effective dose (MED) tends to be small. Therefore great care is required when prescribing these drugs and patients need to be monitored carefully throughout treatment.

Mechanism of action of cytotoxics

Cytotoxics act at various stages of the cell cycle; different drugs work at different stages.