6533b858fe1ef96bd12b6543

RESEARCH PRODUCT

Dose-finding study of oxaliplatin associated to capecitabinebased preoperative chemoradiotherapy in locally advanced rectal cancer

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// Gemma Bruera 1, 2 , Mario Di Staso 3 , Pierluigi Bonfili 3 , Antonio Galvano 4 , Rosa Manetta 5 , Gino Coletti 6 , Roberto Vicentini 7 , Stefano Guadagni 2, 8 , Corrado Ficorella 2, 9 , Ernesto Di Cesare 2, 3 , Antonio Russo 4 and Enrico Ricevuto 1, 2 1 Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy 2 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy 3 Radiotherapy, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy 4 Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy 5 Radiology, S. Salvatore Hospital, L’Aquila, Oncology Network ASL1 Abruzzo, Italy 6 Pathology, S. Salvatore Hospital, L’Aquila, Oncology Network ASL1 Abruzzo, Italy 7 Hepatobiliar-pancreatic Surgery, S. Salvatore Hospital, L’Aquila, Oncology Network ASL1 Abruzzo, Italy 8 Universitary General Surgery, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy 9 Medical Oncology, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy Correspondence to: Antonio Russo, email: antonio.russo@usa.net Keywords: capecitabine; chemoradiotherapy; dose-finding; locally advanced rectal cancer; oxaliplatin Received: December 07, 2017     Accepted: February 27, 2018     Published: April 03, 2018 ABSTRACT Introduction: Proper administration timing, dose-intensity, efficacy/toxicity ratio of oxaliplatin added to fluoropyrimidin should be improved to safely perform two-drugs intensive preoperative chemoradiotherapy in locally advanced rectal cancer (LARC). This dose-finding study investigated recommended oxaliplatin dose, safety of oxaliplatin/capecitabine regimen and preliminary activity. Methods: Schedule: oxaliplatin dose-levels, 35-40 mg/m 2 /week; capecitabine 825 mg/m 2 / twice daily, radiotherapy on rectum/nodes, 50/45 Gy, 45 and 9 boost/45 Gy, in first 5 and subsequent patients, 5 days/week, respectively; for 5 weeks. Pathologic complete response (pCR) 10% was projected in order to positively affect clinical outcome. Results: Seventeen fit <75 years patients enrolled: median age 60; young-elderly 4 (23%); T3/T4, 15/2, N0/N1/N2, 7/9/1. At first dose-level, no dose-limiting toxicity (DLT). At second, 2 DLT, G3 mucositis, G3 thrombocytopenia, in 2/6 patients (33%). Oxaliplatin recommended dose, 40 mg/m 2 /week. Cumulative G3-4 toxicities: mucositis 6%, thrombocytopenia 6%. Limiting toxicity syndromes 18%, 25% in young-elderly, all single site. Objective response rate intent-to-treat 94%. Sphinter preservation 87%, pCR 6%. After 17 months follow-up, progression-free survival and overall survival were not reached. Conclusions: Oxaliplatin can be safely added to preoperative capecitabine-based chemoradiotherapy at the recommended dose 40 mg/m 2 /week, in LARC, with promising pCR and high activity.