Addition of Bevacizumab to XELOX Induction Therapy Plus Concomitant Capecitabine-Based Chemoradiotherapy in Magnetic Resonance Imaging–Defined Poor-Prognosis Locally Advanced Rectal Cancer: The AVACROSS Study

Miguel Nogué; Antonieta Salud; Pilar Vicente; Antonio Arriví; José María Roca; Ferran Losa; José Ponce; María José Safont; Inmaculada Guasch; Isabel Moreno; Ana Ruiz; Carles Pericay; on behalf of the AVACROSS Study Group

doi:10.1634/theoncologist.2010-0285

Addition of Bevacizumab to XELOX Induction Therapy Plus Concomitant Capecitabine-Based Chemoradiotherapy in Magnetic Resonance Imaging–Defined Poor-Prognosis Locally Advanced Rectal Cancer: The AVACROSS Study

^aHospital General de Vic, Vic, Spain;
^bHospital Arnau de Vilanova, Lleida, Spain;
^cHospital General de Granollers, Granollers, Spain;
^dHospital Son Llàtzer, Palma de Mallorca, Spain;
^eHospital Mutua de Terrassa, Terrassa, Spain;
^fHospital General de L'Hospitalet, Hospitalet de Llobregat, Spain;
^gHospital Virgen de los Lirios, Alcoy, Spain;
^hHospital General Universitario de Valencia, Valencia, Spain;
ⁱHospital San Joan de Déu, Manresa, Spain;
^jHospital Municipal de Badalona, Badalona, Spain;
^kHospital de Fuenlabrada, Fuenlabrada, Spain;
^lCorporació Sanitària Parc Taulí, Sabadell, Spain

Correspondence: Miguel Nogué, M.D., Department of Oncology, Hospital General de Vic, C/ Francesc Pla El Vigatà, 1, 08500 Vic, Spain. Telephone: +34 93 702 77 32; Fax: +34 93 885 67 61; e-mail: mnogue{at}chv.cat

Received August 25, 2010.
Accepted January 21, 2011.
First published online in THE ONCOLOGIST Express on April 5, 2011.

Disclosures: Miguel Nogué: None; Antonieta Salud: None; Pilar Vicente: None; Antonio Arriví: None; José María Roca: None; Ferran Losa: None; José Ponce: None; María José Safont: None; Inmaculada Guasch: None; Isabel Moreno: None; Ana Ruiz: None; Carles Pericay: None

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors or independent peer reviewers.

Abstract

Background. Concomitant chemoradiotherapy followed by total mesorectal excision is standard treatment for locally advanced rectal cancer. This approach, however, focuses on local disease control and delays systemic treatment. Induction chemotherapy has the advantage of earlier administration of systemic therapy and may improve distant control. The objective of the current study was to assess the efficacy and toxicity of adding bevacizumab to induction chemotherapy followed by preoperative bevacizumab-based chemoradiotherapy in patients with locally advanced rectal cancer.

Patients and Methods. Eligible patients had high-risk rectal adenocarcinoma defined by magnetic resonance imaging criteria. Treatment consisted of four 21-day cycles of bevacizumab (7.5 mg/kg) and XELOX (capecitabine plus oxaliplatin), followed by concomitant radiotherapy (50.4 Gy) plus bevacizumab (5 mg/kg every 2 weeks) and capecitabine (825 mg/m² twice daily on days 1–15). Surgery was scheduled for 6–8 weeks after chemoradiotherapy. The primary endpoint was pathologic complete response (pCR).

Results. Between July 2007 and July 2008, 47 patients were recruited. Among 45 patients who underwent surgery, pCR was achieved in 16 patients (36%; 95% confidence interval: 22.29%–51.27%), and an additional 17 patients (38%) had Dworak tumor regression grade 3. R0 resection was performed in 44 patients (98%). Most grade 3/4 adverse events occurred during the induction phase and included diarrhea (11%), asthenia (4%), neutropenia (6%), and thrombocytopenia (4%). Eleven patients (24%) required surgical reintervention.

Conclusions. Addition of bevacizumab to induction chemotherapy and chemoradiotherapy is feasible, with impressive activity and manageable toxicity. However, caution is recommended regarding surgical complications.