RESUMEN
The purpose of this trial was to evaluate the feasibility of concurrent paclitaxel/cisplatin and conventional thoracic irradiation in locally advanced non-small cell lung cancer (NSCLC). Ambulatory patients with medically inoperable or unresectable stage II-III NSCLC, and performance status 0-2 were eligible. Patients were not excluded from this trial if they had lost more than 5% of their body weight during the preceding 3 months, and/or if they had small ipsilateral pleural effusion. The initial dose of paclitaxel/cisplatin was 110 and 50 mg/m(2), and was escalated through five dose levels. Four cycles of chemotherapy were planned; the first two cycles were given concurrently with radiotherapy (4 weeks apart), followed by two additional cycles (every 3 weeks). Conventional chest radiotherapy to a total dose of 60 Gy (2 Gy per day) was delivered in 6 weeks. Forty-three patients were enrolled of which 38 were evaluable for response. Dose-limiting toxicities were grade 4 neutropenia (43% of patients) and grade 3 esophagitis (26% of patients) during the chemoradiotherapy phase. Grade > or = 2 acute and late pulmonary toxicity occurred in 10 and 68% of the patients, respectively. In most patients, prompt symptomatic and radiologic improvement was observed with early steroid administration. The volume of lung receiving 15-30 Gy was correlated with late pulmonary toxicity. The overall response was 84% with ten complete and 22 partial responses. The median survival was 16.5 months (95% confidence interval, 9.5 to 25) for those patients evaluable for response. After a median follow-up of 70 months, 5 (13%) patients are alive without evidence of disease. The maximum tolerated dose (MTD) of paclitaxel and cisplatin with concurrent radiotherapy is at dose level 3 paclitaxel (135 mg/m(2)) and cisplatin (75 mg/m(2)). Toxicity, although significant, was manageable in the great majority of the patients. The activity observed with this regimen is particularly noteworthy when considering the advanced nature of these patients, and the fact that patients (N=18) with poor risk factors were included in the study.