Phase 1/2 Study of the Addition of Cisplatin to Adjuvant Chemotherapy With Image Guided High-Precision Radiation Therapy for Completely Resected Gastric Cancer

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• 作者：Rebecca B. Goody ; MBChB^&lowast ; ; Helen MacKay ; MBChB ; MD^&dagger ; ; Bethany Pitcher ; MSc^&Dagger ; ; Amit Oza ; MD^&dagger ; ; Lillian L. Siu ; MD^&dagger ; ; John Kim ; MD^&lowast ; ; Rebecca K.S. Wong ; MBChB ; MSc^&lowast ; ; Eric Chen ; MD^&dagger ; ; Carol Swallow ; MD^§ ; ; Jennifer Knox ; MD^&dagger ; ; Zahra Kassam ; MBBS ; MSc^&lowast ; ; ^‖ ; Bernard Cummings ; MBChB^&lowast ; ; Ron Feld ; MD^&dagger ; ; David Hedley ; MD^&dagger ; ; Geoffrey Liu ; MD^&dagger ; ; Monika K. Krzyzanowska ; MD^&dagger ; ; Robert Dinniwell ; MD ; MSc^&lowast ; ; Anthony M. Brade ; MD ; CM ; PhD^&lowast ; ; Laura A. Dawson ; MD^&lowast ; ; Melania Pintilie ; MSc^&Dagger ; ; Jolie Ringash ; MD ; MSc^&lowast ; ; ^{jolie.ringash@rmp.uhn.on.ca}
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2016
• 出版时间：1 December 2016
• 年：2016
• 卷：96
• 期：5
• 页码：994-1002
• 全文大小：760 K
• 卷排序：96

文摘

Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy.Methods and MaterialsEligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma. Treatment constituted 12 weeks of infusional 5-FU (200 mg/m2/day) with cisplatin added in a standard 3 + 3 dose escalation protocol (0, 20, 30, and 40 mg/m2) during weeks 1, 3, 5, and 7, and an additional week 9 dose in the final cohort. Radiation therapy (45 Gy in 25 fractions) was delivered during weeks 3 to 7. Maximum tolerated dose (MTD) was determined in phase 1 and confirmed in phase 2.ResultsAmong the 55 patients (median age, 54 years; range 28-77 years; 55% male), the median follow-up time was 3.0 years (range, 0.3-5.3 years). Five patients in phase 1 experienced dose-limiting toxicity, and MTD was determined as 4 cycles of 40 mg/m2 cisplatin. Twenty-seven patients were treated at MTD. Acute grade 3 to 4 toxicity rate was 37.0% at MTD and 29.1% across all dose levels. No treatment-related deaths occurred. Fourteen patients experienced recurrent disease. The 2-year overall survival (OS) and relapse-free survival were 85% and 74%, respectively. Median OS has not been reached. Quality of life (QOL) was impaired during treatment, but most scores recovered by 4 weeks.ConclusionCisplatin can be safely delivered with 5-FU–based chemoradiation therapy. Acute toxicity was acceptable, and patient-reported QOL showed the regimen was tolerable. Outcomes are encouraging and justify further study of this regimen.