Paclitaxel, Carboplatin, and Radiation Therapy for Non-Small-Cell Lung Cancer

ABSTRACT: Preclinically, the taxanes appear to potentiate radiation more effectively than do the platinum compounds. In our phase I trial (LUN-17) in patients with advanced non-small-cell lung cancer, we defined the maximum tolerated dose and toxicity profile of concomitant radiation and paclitaxel (Taxol). We then conducted a series of phase II clinical trials in patients with stage IIIA or stage IIIB non-small-cell lung cancer to explore the role of paclitaxel in a combined-modality approach; these trials were based on the very low paclitaxel concentrations needed to enhance radiation in the phase I trial and the relatively high response rate achieved. Our LUN-27 trial of weekly paclitaxel and concurrent radiation for 6 weeks with no adjuvant chemotherapy produced substantial response and survival rates with acceptable toxicity. LUN-56 added weekly carboplatin (Paraplatin) during the initial concurrent phase as well as two cycles of standard-dose paclitaxel and carboplatin. The ongoing LUN-63 phase II study delivers concurrent weekly paclitaxel and carboplatin with hyperfractionated radiation, followed by two cycles of adjuvant paclitaxel and carboplatin, to further improve local control and overall survival. We are currently extending the investigation of concurrent weekly paclitaxel plus radiation in a large-scale, three-arm, randomized phase II trial. To date, toxicity in all trials has been acceptable and compares favorably with other regimens. The major side effect, esophagitis, occurs predictably and is managed easily, abating shortly after therapy is completed. The rates of overall response and 1- and 2-year survival are very encouraging, and phase III evaluation is warranted.[ONCOLOGY 12(Suppl 2):80-86, 1998]

Combination treatment including chemotherapy and radiation therapy has only recently been introduced in clinical trials of lung cancer and some other malignancies. An extensive series of clinical trials[1-4] was conducted to evaluate the significance of in vitro synergy between chemotherapy, particularly cisplatin (Platinol), and radiation therapy in the treatment of lung cancer. Numerous preclinical studies[5-10] have suggested that the taxanes as a group may be more effective potentiators of radiation than are the platinum compounds, but their interactions appear to be complex, and additional preclinical studies are ongoing in hopes of increasing our understanding of the radiation-enhancing mechanisms of these agents. In this presentation we discuss clinical trials[11,12] incorporating paclitaxel (Taxol) and radiation that have been conducted to evaluate the effectiveness and the role for this combination in the treatment of lung cancer.

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