WEEKLY PACLITAXEL AND CISPLATIN WITH CONCURRENT RADIOTHERAPY IN LOCALLY ADVANCED NON-SMALL-CELL LUNG-CANCER - A PHASE-I STUDY

Purpose: Both cisplatin (CDDP) and paclitaxel have shown good antitumo r activity in non-small-cell lung cancer (NSCLC) patients and are able to potentiate the antitumor effects of radiation therapy (RT). This s tudy aimed to determine the maximum-tolerated doses (MTDs) of CDDP and paclitaxel (escalated alternately) when given concurrently with RT an d to define the nature of the dose-limiting toxicity (DLT). Patients a nd Methods: Chemotherapy-naive patients with locally advanced NSCLC re ceived six weekly administrations of a CDDP-paclitaxel combination wit h concurrent local RT. The starting doses of CDDP and paclitaxel were 30 mg/m(2)/wk and 35 mg/m(2)/wk, respectively. RT was initially given at the dose of 1.2 Gy twice daily for 5 days per week for 5 weeks (tot al dose, 60 Gy) and at a single daily dose of 2 Gy for 5 days per week for 6 weeks in the last two cohorts of patients. The drug doses were escalated alternately until DLT occurred in more than one third of the patients in a given cohort. Results: Overall, 25 patients were recrui ted through five different cohorts. All were assessable for toxicity. Esophagitis was the main toxicity and occurred in 16 of 25 patients (6 4%) and was grade 3 or 4 in five of them. At step 3 (CDDP 35 mg/m(2)/w k and paclitaxel 45 mg/ m(2)/wk), two of five patients had to disconti nue treatment because of severe esophagitis and one of these died of c omplications related to grade 4 esophagitis. However, keeping the some doses of chemotherapy and replacing hyperfractionation with a standar d single-day fraction, weekly doses of CDDP and paclitaxel of 35 mg/m( 2) and 45 mg/m(2) could be safely administered. Neutropenia was by far the most relevant hematologic toxicity and occurred in 33 of 141 week ly delivered courses, but it was of grade 4 in only four courses. Subs tantial pulmonary or neurologic toxicity was not observed in this stud y. Two complete responses (CRs) and 13 partial responses (PRs) were ob served, for a 60% overall response rate (95% confidence interval [CI], 39% to 79%). The median survival time was 16 months, with a 66% 1-yea r survival probability. Conclusion: CDDP 35 mg/m(2)/wk and paclitaxel 45 mg/m(2)/wk can be safely administered with concurrent standard RT. The use of hyperfractionation is associated with a more frequent occur rence of severe esophagitis and requires a reduction of the CDDP dose to 30 mg/m(2)/wk. Only future randomized trials will elucidate which o f these two approaches (standard or hyperfractionated RT) is the bette r option to improve the outcome of patients with locally advanced NSCL C. 1417. (C) 1997 by American Society of Clinical Oncology.