Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer

Radiation Oncology

Jürgen Dunst⁸  Dirk Arnold¹  Michael Richter⁶  Wolfgang Wagner²  Claus Rödel⁷  Erik Engel³  Florian Würschmidt⁴  Thomas Reese⁹  Thomas Höhler⁵  Kathrin Dellas⁸ 

[1] Clinic for Medical Oncology, Tumor Biology Center Freiburg, Freiburg, Germany;Department of Radiooncology, Osnabrueck, Germany;Private Practice of Hematology and Medical Oncology, Hamburg, Germany;Private Practice of Radiooncology, Radiologische Allianz, Hamburg, Germany;Prosper Hospital Recklinghausen, Recklinghausen, Germany;Coordination Center for Clinical Trials, Halle, Saale, Germany;University of Frankfurt, Department of Radiooncology, Frankfurt, Germany;Department of Radiooncology, University of Luebeck, Luebeck, Germany;Martin Luther University Halle-Wittenberg, Department of Radiotherapy, Halle, Saale, Germany

关键词: Oxaliplatin;    Capecitabine;    Preoperative radiochemotherapy;    Rectal cancer;    Bevacizumab;   

Others  :  1154176
DOI  :  10.1186/1748-717X-8-90

 received in 2012-12-29, accepted in 2013-04-01,  发布年份 2013

【 摘 要 】

Background

Preoperative radiochemotherapy (RCT) with 5-FU or capecitabine is the standard of care for patients with locally advanced rectal cancer (LARC). Preoperative RCT achieves pathological complete response rates (pCR) of 10-15%. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab and oxaliplatin to preoperative standard RCT with capecitabine.

Methods

Eligible patients had LARC (cT3-4; N0/1/2, M0/1) and were treated with preoperative RCT prior to planned surgery. Patients received conventionally fractionated radiotherapy (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with capecitabine 825 mg/m² bid (d1-14, d22-35) and oxaliplatin 50 mg/m² (d1, d8, d22, d29). Bevacizumab 5 mg/kg was added on days 1, 15, and 29. The primary study objective was the pCR rate.

Results

70 patients with LARC (cT3-4; N0/1, M0/1), ECOG < 2, were enrolled at 6 sites from 07/2008 through 02/2010 (median age 61 years [range 39–89], 68% male). At initial diagnosis, 84% of patients had clinical stage T3, 62% of patients had nodal involvement and 83% of patients were M0. Mean tumor distance from anal verge was 5.92 cm (± 3.68). 58 patients received the complete RCT (full dose RT and full dose of all chemotherapy). During preoperative treatment, grade 3 or 4 toxicities were experienced by 6 and 2 patients, respectively: grade 4 diarrhea and nausea in one patient (1.4%), respectively, grade 3 diarrhea in 2 patients (3%), grade 3 obstipation, anal abscess, anaphylactic reaction, leucopenia and neutropenia in one patient (1.4%), respectively. In total, 30 patients (46%) developed postoperative complications of any grade including one gastrointestinal perforation in one patient (2%), wound-healing problems in 7 patients (11%) and bleedings in 2 patients (3%). pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT < cT and ypN ≤ cN) was achieved in 31 of 69 patients (44.9%). All of the 66 operated patients had a R0 resection. 47 patients (68.1%) underwent sphincter preserving surgery.

Conclusions

The addition of bevacizumab and oxaliplatin to RCT with capecitabine was well tolerated and did not increase perioperative morbidity or mortality. However, the pCR rate was not improved in comparison to other trials that used capecitabine or capecitabine/oxaliplatin in preoperative radiochemotherapy.

【 授权许可】

   
2013 Dellas et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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