Simultaneous radiochemotherapy with paclitaxel in non-small cell lung cancer: a clinical phase I study.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most active single agents available for the treatment of non-small cell lung cancer (NSCLC), with reported response rates of 21% to 24%. Its observed radiosensitizing effect is attributed to its interruption of cell development at the G2/M phase of the cell cycle, when cells are most sensitive to the killing effects of ionizing radiation. This phase I study of paclitaxel and simultaneous radiation therapy in patients with previously untreated, locally advanced inoperable stage IIIA/B NSCLC was designed to determine the maximum tolerated paclitaxel dose, to define the safety and toxicity of this combined modality, and to obtain preliminary data on its activity. Patients received a fixed dose of radiotherapy (1.8 Gy/d, 5 days a week, in shrinking-field technique, for a total dose of 59.4 Gy) and concomitant chemotherapy with a 3-hour infusion of paclitaxel once weekly on day 1, initially at a dose of 45 mg/m2, for 3 weeks. This dose remained constant during study levels 1 to 3, with the number of weeks of treatment increasing to 5 and 7 at levels 2 and 3, respectively. At dose level 4, the paclitaxel dose was increased to 55 mg/m2 over 7 weeks. Of 22 NSCLC patients who entered the study, 18 are evaluable for toxicity and response. Responses included one complete and 10 partial remissions; the other seven patients had minimal improvement. The therapy was well tolerated; no severe adverse events were associated with paclitaxel or radiotherapy. This combined modality appears to be a practicable and effective treatment for NSCLC. The maximum tolerated paclitaxel dose has not yet been reached, and dose escalation is planned.