Phase III comparison of twice-daily split-course irradiation versus once-daily irradiation for patients with limited stage small-cell lung carcinoma

Purpose: Because small-cell lung cancer is a rapidly proliferating tumor, i t was hypothesized that it may be more responsive to thoracic irradiation ( TI) given twice-daily than once-daily. This hypothesis was tested in a phas e III trial. Patient and Methods: Patients with limited-stage small-cell lung cancer wer e entered onto a phase III trial, and all patients initially received three cycles of etoposide (130 mg/m(2) x 3) and cisplatin (30 mg/ m(2) x 3). Sub sequently, patients who did not have progression to a distant site (other t han brain) were randomized to twice-daily thoracic irradiation (TDTI) versu s once-daily thoracic irradiation (ODTI) given concomitantly with two addit ional cycles of etoposide (100 mg/m2 x 3) and cisplatin (30 mg/m2 x 3). The irradiation doses were TDTI, 48 Gy in 32 fractions, with a 2.5-week break after the initial 24 Gy, and ODTI, 50.4 Gy in 28 fractians. After thoracic irradiation, the patients received a sixth cycle of eroposidelcisplatin, fa llowed by prophylactic cranial irradiation (30 Gy/15 fractions) if they had a complete response. Results: Of 311 assessable patients enrolled in the trial, 262 underwent ra ndomization to TDTI or ODTI. There were no differences between the two trea tments with respect to local-only progression rates, overall progression ra tes, or overall survival. The patients who received TDTI had greater esopha gitis(greater than or equal to grade 3) than those who received ODTI (12.3% v 5.3%; P = .05), Although patients received thoracic irradiation encompas sing the postchemotherapy volumes, only seven of 90 local failures were out of the portal of irradiation. Conclusion: When TI is delayed until the fourth cycle of chemotherapy, TDTI does not result in improvement in local control or survival compared with ODTI. (C) 1999 by American Society of Clinical Oncology.