Results of a Phase II Study of High-Dose Thoracic Radiation Therapy With Concurrent Cisplatin and Etoposide in Limited-Stage Small-Cell Lung Cancer (NCCTG 95-20-53) Steven E. Schild, James A. Bonner, Shauna Hillman, Timothy F. Kozelsky, Antonio P.G. Vigliotti, Randolph S. Marks, David L. Graham, Gamini S. Soori, John W. Kugler, Richard C. Tenglin, Donald B. Wender, and Alex Adjei A B S T R A C T Purpose To evaluate the outcome of patients with limited-stage small-cell lung cancer (L-SCLC) treated with cisplatin and etoposide (PE), early prophylactic cranial irradiation (PCI), and high-dose twice-daily thoracic radiotherapy (bid RT). Patients and Methods A total of 76 assessable patients were treated on this phase II trial, which included six cycles of PE. PCI (25 Gy/10 fractions) was delivered during cycle 3 to responding patients. Cycles 4 and 5 included concurrent chemotherapy and thoracic RT (30 Gy/20 bid fractions, a 2-week break, and another 30 Gy/20 bid fractions). Results Of the 76 assessable patients, 74 patients (97%) suffered grade 3 or greater (3+) toxicity and 61 patients (80%) had grade 4 or greater (4+) toxicity. Of these adverse events, grade 3+ hematologic toxicity occurred in 72 patients (95%), and grade 3+ nonhematologic toxicity occurred in 55 patients (72%). Only one (2%) of the 61 patients who received PCI experienced treatment failure in the brain. The 5-year survival rate of the 76 assessable patients was 24% (median, 20 months). The 5-year survival rate of the 64 patients who received thoracic RT was 29% (median, 22 months). The 5-year cumulative incidence of in-field treatment failure was 34%. Conclusion This regimen included a high total dose of bid TRT, which resulted in a favorable 5-year survival rate. Local failure remains a problem that will require additional investigation. Newer technology should allow the safe administration of greater doses of RT, which should improve patient outcome. Data from eight trials were combined to demonstrate a relationship between RT dose fractionation and 5-year survival. J Clin Oncol 25:3124-3129. © 2007 by American Society of Clinical Oncology INTRODUCTION Lung cancer is the leading cause of cancer deaths in the United States, and caused an estimated 169,440 deaths in 2006. 1 Approximately 15% of patients with lung cancer have small-cell lung cancer (SCLC) and of these, 30% have limited-stage disease. 2 The natural history of untreated SCLC includes rapid tumor progression and a median survival of 2 to 4 months. 3 The first major treatment breakthrough was the recognition that SCLC was more responsive to chemotherapy than non–small-cell lung cancer. 4 Since that time, the standard of care for SCLC pa- tients has included systemic chemotherapy. In 1992, two meta-analyses addressed the role of thoracic radiotherapy (RT) in addition to chem- otherapy in limited-stage SCLC (L-SCLC). 2,5 Pig- non et al 5 reported a 3-year survival rate of 14.3% with combined-modality therapy compared with 8.9% with chemotherapy alone (P = .001). This 5.4% difference in 3-year survival was equivalent to the 5.4% difference in 2-year survival (P  .001) reported by Warde and Payne. 2 Prophylactic cranial irradiation (PCI) has also improved survival of pa- tients who achieve a complete response. Auperin et al 6 performed a meta-analysis and found that the 3-year survival rate was 5.4% better for those who received PCI (P = .01). With regard to the specifics of RT administra- tion, twice-daily thoracic RT (bid TRT) was found to improve the outcome of patients with L-SCLC. Turrisi et al 7 reported the findings of the Intergroup From the Mayo Clinic Arizona, Scottsdale, AZ; University of Alabama at Birmingham, Birmingham, AL; Mayo Clinic and Mayo Foundation, Rochester, MN; Cedar Rapids Community Clinical Oncology Program (CCOP), Cedar Rapids; Siouxland Hematology- Oncology Associates, Sioux City, IA; Carle Cancer Center CCOP, Urbana; Illinois Oncology Research Association, CCOP, Peoria, IL; Missouri Valley Cancer Consortium, Omaha, NE; Rapid City Regional Oncology Group, Rapid City, SD; and Roswell Park Cancer Insti- tute, Buffalo, NY. Submitted November 15, 2006; accepted April 18, 2007. Supported in part by Public Health Service Grants No. CA-25224, CA-37404, CA-63849, CA-35113, CA-35103, CA-37417, CA-35269, CA-35448, CA-35101, CA-35272, CA-35415, CA-35101, CA-52352, and CA-60276. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Address reprint requests to Steven E. Schild, MD, Mayo Clinic, Department of Radiation Oncology, 13400 E Shea Blvd, Scottsdale, AZ 85259; e-mail: sschild@mayo.edu. © 2007 by American Society of Clinical Oncology 0732-183X/07/2521-3124/$20.00 DOI: 10.1200/JCO.2006.09.9606 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 25  NUMBER 21  JULY 20 2007 3124 Downloaded from ascopubs.org by 50.16.34.189 on June 21, 2022 from 050.016.034.189 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.