IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

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• 作者：David B. Landau ; MRCP^&lowast ; ; ^{david.landau@kcl.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; Laura Hughes ; NDipSc^&dagger ; ; Angela Baker ; MSc^&Dagger ; ; Andrew T. Bates ; MBBS^§ ; ; Michael C. Bayne ; MD^‖ ; Nicholas Counsell ; MSc^&dagger ; ; Angel Garcia-Alonso ; MD^¶ ; ; Susan V. Harden ; DM^# ; Jonathan D. Hicks ; FRCR^&lowast ; &lowast ; ; Simon R. Hughes ; FRCR^&lowast ; ; Marianne C. Illsley ; MA^&dagger ; &dagger ; ; Iftekhar Khan ; PhD^&dagger ; ; Virginia Laurence ; FRCR^‖ ; Zafar Malik ; FRCR^&Dagger ; ; Helen Mayles ; MSc^&Dagger ; ; William Philip M. Mayles ; PhD^&Dagger ; ; Elizabeth Miles ; MPhil^&Dagger ; &Dagger ; ; Nazia Mohammed ; FRCR^&lowast ; &lowast ; ; Yenting Ngai ; BSc^&dagger ; ; Emma Parsons ; BHSc^&Dagger ; &Dagger ; ; James Spicer ; FRCP^&lowast ; ; Paula Wells ; PhD^§ ; § ; ; Dean Wilkinson ; MSc^&Dagger ; &Dagger ; ; John D. Fenwick ; PhD^‖‖
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2016
• 出版时间：1 August 2016
• 年：2016
• 卷：95
• 期：5
• 页码：1367-1377
• 全文大小：831 K

文摘

To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer.

Patients and Methods

Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined.

Results

Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years.

Conclusions

IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.