Phase III Study of Concurrent Versus Sequential Thoracic Radiotherapy in Combination With Cisplatin and Etoposide for Limited

We treated 231 patients with LS-SCLC. TRT consisted of 45 Gy over 3 weeks (1.5 Gy twice daily), and the patients were randomly assigned to receive either sequential or concurrent TRT. All patients received four cycles of cisplatin plus etoposide every 3 weeks (sequential arm) or 4 weeks (concurrent arm). TRT was begun on day 2 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm.

RESULTS: Concurrent radiotherapy yielded better survival than sequential radiotherapy . The median survival time was 19.7 months in the sequential arm versus 27.2 months in the concurrent arm. The 2-, 3-, and 5-year survival rates for patients who received sequential radiotherapy were 35.1%, 20.2%, and 18.3%, respectively, as opposed to 54.4%, 29.8% and 23.7%, respectively, for the patients who received concurrent radiotherapy. Hematologic toxicity was more severe in the concurrent arm. However, severe esophagitis was infrequent in both arms, occurring in 9% of the patients in the concurrent arm and 4% in the sequential arm.

CONCLUSION: This study strongly suggests that cisplatin plus etoposide and concurrent radiotherapy is more effective for the treatment of LS-SCLC than cisplatin plus etoposide and sequential radiotherapy.

Thoracic Radiotherapy
TRT was begun on day 2 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle of chemotherapy in the sequential arm. It was administered twice daily (1.5 Gy per fraction, with 4 hours or more between fractions) and directed to the primary tumor for a total dose of 45 Gy in 3 weeks. The initial field included the primary disease site with a 1.5-cm margin around the mass, the ipsilateral hilum, the entire width of the mediastinum, and the supraclavicular lymph nodes (only if there was tumor involvement). The initial field in the sequential arm was also based on the pretreatment tumor volume. TRT was suspended if a patient experienced grade 4 hematologic toxicities, radiation pneumonitis or fever, a decrease in arterial oxygen pressure exceeding 10 mmHg, or if a patient had difficulty swallowing a liquid diet. The maximum spinal cord dose was limited to 30 Gy.

After TRT, prophylactic whole-brain irradiation was administered to patients with a complete or near-complete response: a scar-like shadow on chest films but no positive cytology and/or bronchoscopic biopsy. The brain irradiation consisted of 24 Gy in 1.5-Gy fractions twice daily, 5 days per week.

The 24% 5-year survival in this study was impressive and consistent with the 26% reported by Turrisi et al13 in a large intergroup trial. The results of the two trials have updated the recommendation for treatment of patients with LS-SCLC to cisplatin plus etoposide and early, concurrent, twice-daily thoracic radiotherapy. This combined-modality treatment yielded a median survival time of 23 to 27 months and 24% to 26% long-term survivors.