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RTOG 94-10: keenly awaited results validating the best therapeutic strategy for locally advanced non-small cell lung cancer.

About 30% of patients diagnosed with non–small cell lung cancer (NSCLC) have inoperable locally advanced disease. Despite therapeutic advances over the past two decades, these patients’ prognosis remains poor, with a 5-year survival rate of only 10%–15%. Until the late 1980s, radiotherapy was the only treatment option. The Radiation Therapy Oncology Group (RTOG) had shown that local disease control was improved by increasing the total dose to 60 Gy delivered in 30 fractions over 6 weeks (1). The 1990s saw the emergence of both sequential and concurrent combinations of chemotherapy and radiotherapy. A number of randomized phase III trials, and several meta-analyses, showed that chemoradiotherapy was superior to radiotherapy alone in terms of overall survival (2,3). Concurrent therapy seemed to give better results than sequential therapy, but this needed to be demonstrated. The Japanese trial published by Furuse et al. (4) was the first randomized phase III trial to show a statistically significant improvement in overall survival after concurrent chemoradiotherapy, with no increase in esophageal toxicity. In this issue of the Journal, Curran et al. (5) report the results of the RTOG 94-10 study, which compared three schedules: sequential treatment with cisplatin–vinblastine induction chemotherapy followed by radiotherapy at a total dose of 63 Gy (arm 1); a concurrent schedule in which two cycles of cisplatin–vinblastine were administered during the same radiotherapy schedule as in arm 1 (arm 2); and another concurrent schedule combining cisplatin–etoposide chemotherapy with bifractionated radiotherapy at a total dose of 69.6 Gy (arm 3), as used in the RTOG 91-06 study. Arm 2 was first compared with the sequential schedule, which served as the reference treatment, and then arm 3 was compared with the better of the other two arms. The results showed that concurrent cisplatin–vinblastine and radiotherapy statistically significantly increased overall survival compared with the sequential treatment, whereas there was no statistically significant difference between the two concurrent schedules. The benefit persisted at 5 years, as in the French GLOT-GFPC NPC 95-01 study in which the improvement in overall survival observed with the concurrent schedule was stable at 5 years (18.5% vs 8.5%) and at 7 years (15% vs 5.8%) (6, 7). The RTOG 94-10 study, already presented partially on two occasions, has been awaited for several years. Individual data from this study were included in the NSCLC Collaborative Group meta-analysis of six randomized trials that confirmed the superiority of concurrent treatment (8). The gain in overall survival was associated with better local control. As expected, acute esophageal toxicity was more