24.03.7 Other Treatments

A number of other agents that fall outside the regular classifications are used as anticancer treatments. Included in this group are the platinum coordination complexes such as cisplatin and carboplatin (both used in the treatment of metastatic testicular cancer, ovarian cancer and bladder carcinoma) and oxaliplatin (used in treatment of advanced colorectal cancer). All of these agents work in a similar way although cisplatin has severe toxicity issues. They crosslink with DNA through a guanine nucleobase and the resulting cytotoxic lesion inhibits both DNA replication and RNA synthesis. Adverse effects include severe, persistent vomiting (so anti-emetic agents should be used in conjunction), nephrotoxicity and ototoxicity.

Irinotecan (treatment of colorectal carcinoma) and topotecan (treatment of metastatic ovarian cancer, small-cell lung cancer) exert their actions by inhibition of topoisomerase I, an enzyme essential for the replication of DNA in human cells. In contrast, etopside (treatment of acute lymphoblastic leukaemia, lung cancer, testicular cancer) targets a second topisomerse enzyme, topoisomerase II and results in arrest of the cells in the late S to G2 phase of the cell cycle. These compounds cause the common adverse effects associated with anticancer drugs, however, etopside may cause leukaemia to develop.

Imatinib belongs to a new class of anticancer agents. These perturb intracellular signalling pathways. Imatinib, which is used to treat chronic myeloid lymphoma and gastrointestinal stromal tumours, works by blocking the unregulated expression of tyrosine kinases associated with tumour growth thus inhibiting cell proliferation. Unusual adverse effects associated with this drug include thrombocytopaenia, neutropaenia, oedema and gastrointestinal bleeding. Very rare instances of stroke and congestive heart failure have been reported with the use of this drug.

Recombinant DNA technology has proved particularly useful in producing usable quantities of low abundant biomolecules for use as treatments. In particular, production of interferons has proved particularly useful. These are proteins released by lymphocytes in response to pathogens or tumour cells. Two subtypes, interferon a2a and a2b have been shown to be particularly effective in the treatment of leukaemia, melanoma and AIDS-related Kaposi’s sarcoma.   

Comments