Principles of chemotherapy

Combination chemotherapy is the mainstay of treatment for most childhood cancer, either alone or in combination with surgery and radiotherapy. Sequential national and international studies of combinations of cytotoxic drugs have resulted in improvements in the outcomes for childhood cancer. These improvements have required careful attention to be paid to the maintenance of dose intensity and the optimisation of supportive care to manage acute toxicity. Increased understanding of the molecular basis of childhood cancer is now leading to the introduction of more targeted anti-cancer drugs, usually in combination with existing conventional agents. This will allow the remaining stubbornly drug-resistant childhood cancers to be treated more effectively, but will also allow does reduction of conventional agents in sensitive tumour types, reducing both acute and chronic toxicity. Increasing understanding of both pharmacokinetics and pharmacogenomics offers the opportunity for more personalized anti-cancer treatment, to optimize drug dosing for an individual, and to reduce their toxicity. This review will give an outline of the molecular basis for anticancer drug action, will look at some specific types of cytotoxic agent, and describe the principles for combining these into treatment protocols. It will describe short and long term side effects of chemotherapy, and how these often limit what can be given. The importance of pharmacokinetics, in understanding how drugs are handled by children of different ages, and increasingly these days, as a means of individualising drug dosing, will be discussed. Finally the growing importance of pharmacogenomics as a way of predicting both response and toxicity will be described.