Oncotarget

Clinical Research Papers:

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

Gemma Bruera, Mario Di Staso, Pierluigi Bonfili, Antonio Galvano, Rosa Manetta, Gino Coletti, Roberto Vicentini, Stefano Guadagni, Corrado Ficorella, Ernesto Di Cesare, Antonio Russo _ and Enrico Ricevuto

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Oncotarget. 2018; 9:17906-17914. https://doi.org/10.18632/oncotarget.24665

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Abstract

Gemma Bruera1,2, Mario Di Staso3, Pierluigi Bonfili3, Antonio Galvano4, Rosa Manetta5, Gino Coletti6, Roberto Vicentini7, Stefano Guadagni2,8, Corrado Ficorella2,9, Ernesto Di Cesare2,3, Antonio Russo4 and Enrico Ricevuto1,2

1Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy

2Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy

3Radiotherapy, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy

4Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy

5Radiology, S. Salvatore Hospital, L’Aquila, Oncology Network ASL1 Abruzzo, Italy

6Pathology, S. Salvatore Hospital, L’Aquila, Oncology Network ASL1 Abruzzo, Italy

7Hepatobiliar-pancreatic Surgery, S. Salvatore Hospital, L’Aquila, Oncology Network ASL1 Abruzzo, Italy

8Universitary General Surgery, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy

9Medical Oncology, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy

Correspondence to:

Antonio Russo, email: [email protected]

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/m2/week; capecitabine 825 mg/m2/ 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/m2/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/m2/week, in LARC, with promising pCR and high activity.


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