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Phase II study of preoperative radiotherapy and concomitant weekly intravenous oxaliplatin combined with oral capecitabine for stages II–III rectal cancer

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Abstract

Introduction

A prospective phase II study was conducted to assess the clinical activity and tolerability of oxaliplatin, capecitabine, and radiotherapy (RT) for neoadjuvant therapy of stages II–III rectal cancer.

Materials and methods

Patients with histologically confirmed stages II–III (T3–T4 and/or N+) resectable rectal adenocarcinoma were eligible. Capecitabine was administered at 825 mg/m2 twice daily for 5 days/week and oxaliplatin at 50 mg/m2 on day 1 weekly for 5 weeks starting the first day of RT (before RT). RT consisted of a total dose of 45 Gy delivered in 25 fractions of 1.8 Gy, 5 days per week, for 5 weeks.

Results

A total of 46 patients were included (35 male, 10 female, median age 62 years). TNM Stage was T3 in 43 patients and T4 in 2. Twenty-eight patients had suspected nodal involvement. The intended chemoradiation treatment was completed in 94 % patients. Grade 3/4 toxicity included lymphocytopenia (6 patients), diarrhea (4 patients), emesis (2 patients), asthenia (3 patients), anorexia (1 patient), and hepatic toxicity (1 patient). Grade 1 neurotoxicity occurred in 18 patients, Grade 2 neurotoxicity in 3, and Grade 1 palmoplantar erythrodysesthesia in 2. Forty-two patients underwent surgery (complete resection 95 %, sphincter-saving operation 55 %). The overall pathologic response rate was 83 %, with a pathologic complete response (pCR) rate of 11.9 % (95 % CI 4.0–25.6).

Conclusions

The pCR rate observed with oxaliplatin plus capecitabine and RT did not reach the pre-specified criteria of efficacy in this trial, which is in line with recent results of randomized phase III trials.

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Acknowledgments

We thank the patients and the medical and nursing staff of all the participating institutions, Inma Ruiz de Mena from the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) for logistic support, AAIPharma for monitoring, statistics and data management. The study was supported by an unrestricted grant from Roche and Sanofi Aventis, Spain.

Conflict of interest

Margarita Majem, Matilde Navarro, Ferran Losa, Vicente Alonso, Manel Gallén, Pilar Escudero, Encarnación González, have no potential conflicts of interest. Consultant or advisory role: Ramon Salazar, Roche: Bartomeu Massutí, Roche; Enrique Aranda, Roche; Fernando Rivera, Roche and Sanofi Aventis. Travel and Research Grants: Fernando Rivera, Roche and Sanofi Aventis. Honoraria: Bartomeu Massutí, Roche; Manuel Benavides; Sanofi Aventis.

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Correspondence to Ramon Salazar.

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On behalf of the Spanish Cooperative Group for Digestive Tumor Therapy (TTD).

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Salazar, R., Navarro, M., Losa, F. et al. Phase II study of preoperative radiotherapy and concomitant weekly intravenous oxaliplatin combined with oral capecitabine for stages II–III rectal cancer. Clin Transl Oncol 14, 592–598 (2012). https://doi.org/10.1007/s12094-012-0846-7

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  • DOI: https://doi.org/10.1007/s12094-012-0846-7

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