Paclitaxel and Vinorelbine in Non-Small-Cell Lung Cancer

By combining active agents with different mechanisms of action and/or toxicity to prevent drug resistance, combination chemotherapy can offer better therapeutic results for cancer patients than single-agent treatment. The advantages of combination chemotherapy have been demonstrated in the treatment of Hodgkin’s disease, non-Hodgkin’s lymphoma, breast cancer, testicular carcinoma, and small-cell lung cancer.[1] Vinorelbine (Navelbine) and paclitaxel (Taxol) affect microtubular functions but act at different binding sites and in different steps of mitosis. Vinorelbine inhibits the formation of microtubules from tubulin dimers, whereas paclitaxel stabilizes and prevents depolymerization of microtubules.[2,3] Adams has demonstrated synergistic cytotoxicity of these two agents against MCF-7 and MDA-MB-231 breast cancer cells in vitro.[4] In addition, Knick et al have demonstrated improved survival with the combination of vinorelbine and paclitaxel vs either agent alone (80% vs 0%, respectively) in treating mice bearing P388 leukemic cells, without increasing toxicities.[5] We have also shown increased cytotoxicity of vinorelbine and paclitaxel against A549 cells (human adenocarcinoma of the lung), as compared with either agent alone. When used as first-line therapy for advanced non-small-cell lung cancer (NSCLC), vinorelbine alone produces an objective response rate of 14% to 30% and a 1-year survival rate of 25% to 30%.[6,7] When used as a single agent in patients with metastatic non-small-cell lung cancer, paclitaxel is associated with a 21% to 24% objective response rate and a 40% 1-year survival rate.[8,9] These results clearly demonstrate that vinorelbine and paclitaxel are among the most active drugs when used as single agents or in combination chemotherapy regimens for the treatment of non-small-cell lung cancer. Because there is no standard second-line therapy for patients with refractory and/or metastatic non-small-cell lung cancer, who have an urgent need for effective treatment, we chose to study this combination in an in vitro model and in a clinical trial.