Cytotoxic means destructive to living cells. Cytotoxic drugs possess anti-cancer properties but also have the potential to damage normal tissue. Their use is twofold: to eliminate a cancer and so prolong life; or to alleviate distressing symptoms, especially in patients whose prospects of a cure are poor. In many cases CHEMOTHERAPY with cytotoxic drugs is combined with surgery, RADIOTHERAPY or both. Chemotherapy may be used initially to reduce the size of the primary TUMOUR (a process called neoadjuvant therapy) before using radiotherapy or surgery to eliminate it. Cytotoxic drugs may also be used as adjuvant treatment to prevent or destroy secondary spread of the primary tumour that has either been removed by surgery or treated with radiotherapy. All chemotherapy causes side-eﬀects: the ONCOLOGIST – a specialist in cancer treatment – has to strike a balance between hoped-for beneﬁts and acceptable (for the patient) toxic eﬀects, which include nausea and vomiting, BONE MARROW suppression, ALOPECIA (hair loss) and teratogenic eﬀects (see TERATOGENESIS).
Cytotoxic drugs are used either singly or in combination, when an enhanced response is the aim. Chemotherapy of cancer is a complex process and should be supervised by an oncologist in co-operation with physicians, surgeons, radiotherapists and radiologists as appropriate.
The cytotoxic drugs include:
(1) The alkylating agents which act by damaging DNA, thus interfering with cell reproduction. Cyclophosphamide, ifosfamide, chlorambucil, kelphalan, busulphan, thiotepa and mustine are examples of alkylating agents.
(2) There are a number of cytotoxic antibiotics used in the treatment of cancer – doxorubicin, bleomycin, dactinomycin, mithramycin and amsacrine are examples. They are used primarily in the treatment of acute leukaemia and lymphomas.
(3) Antimetabolites – these drugs combine irreversibly with vital enzyme systems of the cell and hence prevent normal cell division. Methotrexate, cytarabine, ﬂuorouracil, mercaptopurine and azathioprine are examples.
(4) Another group of cytotoxic drugs are the vinca alkaloids such as vincristine, vinblastine and vindesima.
(5) Platinum compounds such as carboplatin, cisplatin and oxaliplatin are eﬀective. All of them are given intravenously, but the latter two tend to have more unpleasant side-eﬀects. Carboplatin and cisplatin are useful in the treatment of solid tumours. Carboplatin, a derivative of cisplatin, is given intravenously in ovarian cancer and in small-cell lung cancer. Better tolerated than cisplatin, the drug causes less nausea and vomiting, nephrotoxicity, neurotoxicity and ototoxicity. Where platinum-containing therapy has failed, intravenous treatment with paclitaxel may be tried. With only a limited success rate, it is relatively toxic and should be carefully supervised; responses, however, are sometimes prolonged.
Also of increasing importance in treating cancer are interferons. These are naturally occurring proteins with complex eﬀects on immunity and cell function. Although toxic, with numerous adverse eﬀects, they have shown some anti-tumour eﬀect against certain lymphomas and solid tumours.