Paclitaxel-based therapy in non-small-cell lung cancer: improved third generation chemotherapy

Abstract

The newer or 'third generation' chemotherapeutic agents (paclitaxel, docetaxel, vinorelbine, gemcitabine, irinotecan, topotecan) have all recently been shown to have substantial activity against non-small-cell lung cancer (NSCLC). Many of these agents are now being incorporated into the therapy for patients with advanced disease. Paclitaxel was the first 'third generation' drug to be studied. The use of paclitaxel and carboplatin has proven to be a well tolerated and quite active regimen with one-year survival in patients with stage IV disease of about 40% and two-year survival of about 20%. These survival rates are at least twice as good as previous platinum-based regimens. We have simplified the administration of paclitaxel by using a one-hour infusion and many other investigators and clinicians have followed suit. The results are equivalent to a three-hour infusion schedule. Given the degree of activity in patients with stage IV disease, it is imperative to begin neoadjuvant and adjuvant trials with the newer drugs and drug combinations. We and others have started a neoadjuvant strategy which has proven to be feasible and most patients tolerate surgery well. While the results are quite preliminary, we have seen some complete pathologic responses (about 20%) and are encouraged by these early data. In addition, we have routinely used adjuvant paclitaxel and carboplatin in patients with stage IB-IIIA disease who have been previously resected. Radiotherapy and a weekly schedule of paclitaxel and carboplatin have been incorporated for patients with stages II-IIIB (selected IIIB patients). Randomized comparisons are certainly needed in the neoadjuvant and adjuvant arena and the other 'third generation' drugs need to be quickly evaluated. We have chosen to add a third agent to paclitaxel and carboplatin. The evaluation of several triple combinations including the addition of gemcitabine, vinorelbine and topotecan, respectively to the paclitaxel-carboplatin combination has been completed. Preliminary results from these trials will be briefly summarized and plans for additional studies of the newer agents will also be discussed. Studies to learn the appropriate combinations, doses and schedules of the newer drugs in concert with radiotherapy and/or resection are also urgently needed. Since the newer 'third generation' drugs appear to genuinely improve the survival of patients with stage IV disease, it is likely that incorporation of these more active agents into therapy for lower stages of disease will make an even greater impact on overall survival for patients with this common neoplasm.