An introduction to chemotherapy
The origins of chemotherapy lie in the use of biological warfare during the First World War, in the form of mustard gas in 1917. This caused blistering of the skin, conjunctivitis and after about 4 days victims developed myelosuppression. In 1944, the first patient was treated using nitrogen mustard for a lymphoma and achieved a temporary remission but later died of bone marrow failure.
Chemotherapy involves the use of pharmacological agents to kill tumour cells. It can be effective in treating both primary tumours and metastatic spread. Chemotherapy agents act at different stages of the cell cycle and exert their effects primarily by three mechanisms:
- altering the chemistry of nucleic acids;
- interfering with DNA or RNA synthesis;
- disrupting mechanisms of cell division.
Most of the common agents act in a non-selective manner, not only damaging cancer cells but also affecting normal dividing cells such as hair follicles, bone marrow and gastrointestinal mucosa. This produces side effects that limit the dose that can be administered and the recovery time before the next dose can be given. The adverse effects of treatment are discussed in Chapter 22.
Most chemotherapy is given as a combination of drugs administered intravenously on an intermittent basis. An individual cycle is repeated every 21–28 days and a course of treatment typically comprises six cycles of chemotherapy. Malignant cells have less capacity for repair than normal cells and intermittent dosing exploits the fact that tumour cells recover from cytotoxic damage more slowly than normal cell populations. Each sequential treatment cycle aims to deplete tumour cells, while breaks between cycles give normal stem cells time to recover.
Chemotherapy drug dose is usually calculated from the surface area of the patient (based on height and weight). The goals and approach to treatment are outlined in Chapter 18.
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