Cytotoxic Drugs

Cytotoxic drugs were the first class of drugs used to effectively treat neoplasms. Nitrosourea was the first drug developed. These drugs target DNA or metabolic steps which are crucial for cell division, thus leading to apoptosis (cytotoxic). They are broadly classified as alkylating agents, antimetabolites, natural products, and miscellaneous drugs. Alkylating agents cause interstrand linking of DNA through alkylation. Platinum compounds also cause inter- and intra-strand linkage but by forming DNA adducts. Antimetabolites act by inhibiting purine, pyrimidine, or both syntheses. Natural products include microtubule-damaging drugs like vinca alkaloids and taxanes; camptothecins and epipodophyllotoxins—which act by interfering with topoisomerase function; and anti-tumour antibiotics—which cause breaks in DNA strands. Miscellaneous group includes drugs with an entirely different mechanism, for example, tretinoin (ATRA) and arsenic trioxide (ATO) induce cell differentiation. There are many newer analogues in each class of drugs. The essential pharmacokinetic parameters and important indications which help to differentiate between these analogues are presented in the chapter. Though cytotoxic chemotherapy has offered hope to patients, the use of these drugs is accompanied by a number of adverse drug reactions (ADRs) mainly due to their action on normal rapidly dividing cells of our body. Currently targeted chemotherapy has gained importance in research due to their lesser incidence of ADRs.