Anticancer Drugs: Classification and Principles

Anticancer Drugs: Classification and Principles

1. Definition & scope of cancer chemotherapy

• Cancer chemotherapy = the treatment of malignant disease with drugs that either kill cancer cells or modify their growth; the malignant cell is conceptually viewed as an "invader," by analogy with antimicrobial chemotherapy (KDT 8e Ch.64, pp.915, 933).
• Two fundamental differences from antimicrobial chemotherapy explain why anticancer drugs are among the most toxic agents in therapeutics (KDT 8e Ch.64, p.933):
  • Limited selectivity — bacteria differ markedly in metabolism from the host, but malignant cells are host cells with deranged growth/differentiation regulation and relatively minor other differences; therefore selective killing is hard, and special measures must be used to enhance tumour selectivity.
  • Loss of immune surveillance — infecting microorganisms are amenable to host defence mechanisms, but these are absent or minimal against cancer cells.
  • The discovery of unique tumour antigens and oncogenes (e.g. the BCR-ABL tyrosine kinase in CML) now provides specific molecular targets that partly overcome the selectivity problem (KDT 8e Ch.64, p.933).
• Few categories of medication have a narrower therapeutic index and greater potential for harm than anticancer drugs; safe use demands a thorough grasp of mechanism, clinical pharmacokinetics, drug interactions and adverse effects (G&G 14e Ch.69, p.1337).
• Modern cancer pharmacotherapy is multimodal — drugs are used with surgery, radiotherapy and immunotherapy in a combined-modality approach, especially for solid and metastatic tumours (KDT 8e Ch.64, p.915).
• Anticancer drugs are increasingly used in non-malignant disease and are now standards of care for several: rituximab (autoimmune disease), methotrexate and cyclophosphamide (rheumatoid arthritis), 6-mercaptopurine (Crohn's), methotrexate and azathioprine (organ transplantation), hydroxyurea (sickle cell anaemia), methotrexate (psoriasis), ranibizumab and aflibercept (wet macular degeneration) (G&G 14e Ch.69, p.1337).
• The field is now a highly specialised one handled by oncology specialists with a multidisciplinary team; standard textbooks present only the general principles and an outline (KDT 8e Ch.64, p.915).