Daily paclitaxel and thoracic radiation therapy for non-small cell lung cancer: preliminary results.

Platinum-based combination chemotherapy plus thoracic radiation prolongs survival for patients with stage III non-small cell lung cancer. Paclitaxel demonstrates significant clinical antitumor activity in this disease and potentiates the effects of ionizing radiation by arresting cells at the sensitive G2/M cell cycle phase. The optimal schedule of paclitaxel administered concomitantly with thoracic radiation has not been established. The preliminary results of this phase I trial, which was designed to define the dose-limiting adverse event and the maximum tolerated dose of paclitaxel administered daily before each fraction of thoracic radiation, are being presented. Twenty-nine patients with inoperable clinical stage II to IIIB non-small cell lung cancer received two 21-day cycles of primary chemotherapy with carboplatin and paclitaxel. Six weeks from the initiation of therapy, daily paclitaxel was administered intravenously over 1 hour without premedication before 68 Gy of thoracic radiation in 34 fractions. Twenty-six patients completed concomitant daily paclitaxel with radiation and are evaluable for toxicity. Early radiation esophagitis was the dose-limiting toxicity at the 15 mg dose level. A daily paclitaxel dose of 10 mg or 6 mg/m2 and 68 Gy of thoracic radiotherapy are recommended for further study. Preliminary data from this dose-escalation trial suggest that this combined modality treatment with concurrent radiation and daily paclitaxel following primary induction therapy for stage II to III non-small cell lung cancer is feasible. The observed adverse effects within the radiation field suggest active radiosensitization by low-dose daily paclitaxel.