Introduction to Medical Oncology


Spiffistan, 2007


Discovery of cytotoxic agents has been primarily empirical; based on observation and experience.  The screening of natural products, antibiotics and chemical synthetics and testing in in vitro and in vivo tumour model systems including human tumour cell lines has led to the approval and availability of > 50 cytotoxic agents.


Cytotoxics target DNA (direct toxicity, interference with replication and synthesis) and the process of cell division.  Many cytotoxics share mechanisms of action.








 5FU, cytarabine, purine analogs, methotrexate

 mainly active during synthetic phase of cell cycle, structural analogs of normal metabolite that are incorporated into DNA/RNA causing  false message transmission enzyme inhibitors for the synthesis of essential compounds

 mitotic inhibitors

vincas, taxanes 

mainly active during mitotic phase, vincas bind to tubulin causing metaphase arrest, taxanes enhance microtubule assembly forming a stable nonfunctional microtubule

 alkylating agents

 cyclophosphamide, cisplatin, carmustine

DNA cross linking inhibiting DNA replication and RNA transcription 

 antitumour antibiotics

 anthracyclines, bleomycin

 intercalating agents, insertion between DNA base pairs

 topoisomerase inhibitors

 camptothecins, anthracyclines, etoposide

inhibit enzymes that break and reseal DNA strands 






Sites of Action
















 Tumour antibodies










 Vinca alkaloids


















Theory points to need to give repeated doses of cytotoxic agents. The optimal timing of repeat doses for individual drug depends on whether it is cell cycle phase specific and the normal tissue toxicity of drug and its recovery period.

Cell cycle specific agents  (in S or M phase) are more active when give frequently or continuously.  This allows new cells not yet in cycle to enter into vulnerable state. So, repeated smaller doses are preferable to fewer larger doses.


All models of tumour growth support that antineoplastic drugs be administered:

  • in combination

  • in an alternating fashion

  • at the maximally tolerated dose

  • over the shortest time possible


Dose, dose intensity and schedule are important contributors to outcome in oncology.

 The dose intensity is the drug dose per unit of time.

Drugs are given in doses and schedules to balance the toxic effects and efficacy. Efficacy is more dependent on inherent sensitivity of the tumour to a particular agent than on how the agent is given.

Most gains are to be made from combination treatment. Single agent treatment has limited value except in rare cases.


Ideal combinations of drugs are those which have:

  • activity in the same tumour type

  • different  mechanisms of action (and resistance)

  • non-overlapping toxicity (though this is not possible with full doses of each drug)

  • acceptable side effects



Toxicity occurs acutely and in the long term.




 nausea and vomiting







 almost all

 local complications of extravasation


 hepatic toxicity





 cyclophosphamide, ifosfamide


cerebellar toxicity with arabinoside



second malignancies

alkylating agents, anthracyclines


anthracyclines, cyclophosphamide




bleomycin, cyclophosphamide





gonadal (sterility)



vincas, taxanes, platinum, thalidomide




Toxicity Prevention:

  • prophylactic antiemetics

  • vascular access devices minimize extravasation

  • adequate pre/post hydration

  • stop below known toxic cumulative doses

  • dose reduction / delay

  • growth factor support

  • prophylactic antibiotics

  • mouth care

  • cytoprotectants / rescue agents

Maintain a high index of suspicion and intervene early!





Limits of cytotoxics

  • only 3-4 drug combination regimens are possible

  • DNA synthesis/replication as a target is limited because of normal tissue toxicity