Phase III trial of concurrent thoracic radiotherapy (TRT) with either the first cycle or the third cycle of cisplatin and etoposide chemotherapy to determine the optimal timing of TRT for limited-disease small cell lung cancer.

Abstract

7004 Background: Concurrent thoracic radiotherapy (TRT) with chemotherapy has been regarded as optimal treatment for limited-disease small cell lung cancer (SCLC). However, the issue on how early TRT should be commenced is not yet defined. Methods: A total of 219 patients with limited-disease SCLC, who were enrolled from July 2003 to June 2010, received four cycles of cisplatin plus etoposide (cisplatin 70 mg/m2 on day 1 and etoposide 100 mg/m2 on days 1 to 3 every 3 weeks). We randomly assigned these patients to receive concurrent TRT, beginning with the first cycle (initial arm) or the third cycle (delayed arm) of chemotherapy. In both arms, patients received 2.1 Gy once-daily in 25 fractions over a period of five weeks, with a total dose of 52.5 Gy. Patients with partial or complete response were recommended to receive prophylactic cranial irradiation (PCI). Results: Approximately 82% of patients completed planned four cycles of chemotherapy with 52.5 Gy TRT (81.1% and 82.4% in the initial and delayed arm, respectively). After a median follow-up of 4.9 years (range, 1.2 – 8.1 years), the median overall survivals were 24.1 and 26.8 months (P=0.60) in the initial and delayed arm, respectively. Progression-free survival and complete response rates were 12.2 vs. 12.1 months (P=0.94) and 36.0% vs. 38.0% (P=0.77) in the initial and delayed arms, respectively. PCI was given to 49.5% and 55.6% of patients in the initial and delayed arms, respectively (P = 0.37). Febrile neutropenia was significantly more frequent with the initial arm, occurring in 21.6% of patients, as compared with 10.2% in the delayed arm (P = 0.02). All grade esophagitis occurred in 45.0% and 37.0% of the initial and delayed arms, respectively (p = 0.23). Conclusions: TRT (52.5 Gy, once daily) beginning with the third cycle of chemotherapy showed comparable survival outcomes and complete response rates with TRT beginning with the first cycle of chemotherapy, with a lower frequency of febrile neutropenia.