Single-agent paclitaxel and radiation for non-small cell lung cancer

Lung cancer must be viewed as a systemic disease, and control of latent metastases at both regional and systemic sites is the goal of therapy. Combined modalities have emerged as the dominant strategy with which to manage latent metastases, and paclitaxel has several properties, including a modest toxicity profile, significant activity, and radiosensitization potential, which contribute to its effectiveness in this setting. In phase I clinical trials, paclitaxel was administered weekly in combination with radiation therapy (60 Gy) in the outpatient setting to patients with stage III non-small cell lung cancer (NSCLC). The dose-limiting toxicity, which occurred at a paclitaxel dose of 70 mg/m2/wk, was esophagitis; thus, a paclitaxel dose of 60 mg/m2/wk was recommended for phase II evaluation. In the phase II trial in patients with inoperable stage IIIA or stage IIIB NSCLC, paclitaxel 60 mg/m2/wk (for 6 weeks) plus radiation therapy (60 Gy) resulted in an overall response rate of 86%. The overall median survival was 20 months, and projected 1-, 2-, and 3-year survival rates were 60%, 54%, and 39%, respectively. These results demonstrate the feasibility and potential efficacy of this combination in the treatment of regionally advanced malignancies. When paclitaxel is administered using this schedule, it appears to exhibit an altered pattern of toxicity, with much lower incidences of hematologic and neurologic toxicities, which may improve the overall therapeutic index of this combination. Until curative systemic therapy is developed, combined modality approaches offer the greatest potential for long-term control of advanced NSCLC. Based on the observed activity and toxicity profile, concurrent radiation therapy plus paclitaxel offers significant clinical utility for control of both local and distant metastatic disease.