VINORELBINE - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND CLINICALUSE IN CANCER-CHEMOTHERAPY

Vinorelbine is a semisynthetic vinca alkaloid with a broad spectrum of antitumour activity The drug is effective as a single agent in inoper able/advanced non-small cell lung cancer (NSCLC), producing objective response rates of about 15 to 30%, and as first-line or later chemothe rapy for metastatic spread in advanced breast cancer. Combining vinore lbine with standard chemotherapeutic regimens improves response rates in these indications compared with vinorelbine monotherapy: in NSCLC r esponse rates increase to 30 to 50% when vinorelbine is administered w ith cisplatin. importantly survival was prolonged by a further 9 weeks with this combination in a trial in >600 patients with NSCLC. Compara tive trials evaluating vinorelbine in women with advanced breast cance r are few at present. However results suggest greater efficacy for vin orelbine than for melphalan as second-line chemotherapy, and similar e fficacy for vinorelbine plus doxorubicin compared with doxorubicin plu s 2 other drugs as first-line chemotherapy. Vinorelbine has tended to yield superior response rates when compared with vindesine, and appear s to have greater haematological toxicity (i.e. granulocytopenia) but less neurological toxicity (peripheral neuropathy, constipation, loss of deep tendon reflexes) than this agent. Myelosuppression is the most frequent cause of vinorelbine treatment delay or dose reduction. Othe r consequences of vinorelbine therapy are those typically seen with an tineoplastic agents, such as diarrhoea, nausea and vomiting, and alope cia. However these are rarely severe. Early clinical investigations in dicate that the antitumour effects of vinorelbine in other malignancie s including ovarian carcinoma, lymphoma and head and neck cancer warra nt further exploration, as does the efficacy of the drug relative to s tandard approaches and its possible beneficial effects on quality of l ife of cancer patients. Clarification is also required of the feasibil ity of an oral dosage form, which in preliminary investigations has sh own some efficacy in NSCLC, but a variable response rate and high inci dence of gastrointestinal disturbances in women with breast cancer.. T hus, vinorelbine as a single agent or combined palliative therapy is e ffective against advanced NSCLC, and as first- or second-line chemothe rapy in advanced breast cancel: This semisynthetic vinca alkaloid has a manageable tolerability profile and potential for use in other malig nancies and as an oral formulation. With these attributes, vinorelbine is a valuable option which extends the range of treatments available for these difficult-to-treat malignancies.