Anticancer Drugs: Classification and Principles

Introduction & treatment intent

• Definition — cancer chemotherapy is the treatment of malignant disease with drugs that kill cancer cells or modify their growth; the malignant cell is conceptually an invader, by analogy with antimicrobial chemotherapy.
• Why so toxic — anticancer drugs have one of the narrowest therapeutic indices in all of medicine, for two reasons: limited selectivity (malignant cells are host cells with deranged growth regulation and only minor other differences) and loss of immune surveillance against tumour cells. Unique tumour antigens/oncogenes (e.g. BCR-ABL in CML) now provide molecular targets that partly overcome the selectivity problem.
• Multimodal & non-malignant use — drugs are combined with surgery, radiotherapy and immunotherapy (combined-modality approach); several are now standards of care in non-malignant disease — methotrexate/cyclophosphamide (RA), 6-mercaptopurine (Crohn's), azathioprine (transplantation), hydroxyurea (sickle-cell), methotrexate (psoriasis).
• Treatment intent — curative in a defined chemosensitive group (acute leukaemias, choriocarcinoma, Hodgkin's disease, Wilms', Ewing's & testicular tumours, Burkitt's lymphoma); palliative (shrinkage/symptom-relief without cure) in breast, ovarian, prostate, myeloma, CLL/CML, non-Hodgkin lymphoma, small-cell lung cancer.
  • Adjuvant — given after surgery/radiotherapy to eliminate residual micrometastases (early breast, lung, colonic cancer).
  • Neoadjuvant — given before definitive local treatment to shrink locally advanced tumours and permit less mutilating surgery (head-and-neck, breast, oesophageal cancer, sarcomas).