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.
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.
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