Preoperative treatment with capecitabine, bevacizumab and radiotherapy for primary locally advanced rectal cancer – A two stage phase II clinical trial☆

Abstract 

Background and purpose

The aim of this single-arm multicenter phase II clinical trial was to assess the feasibility and tolerability of preoperative radiotherapy and simultaneous capecitabine and bevacizumab. Secondary endpoints were downstaging-rate and induction of complete pathological response.

Material and methods

Patients with cT3 rectal cancer were eligible. Capecitabine (825mg/sqm twice daily on radiotherapy-days weeks 1–4) and bevacizumab (5mg/kg on days 1, 15 and 29) were administered concurrently to pelvic radiotherapy (1.8Gy daily up to 45Gy in 5weeks). Surgery followed 6–8weeks later. A two-stage trial was designed with early termination at eight patients if more than three patients had experienced a common toxicity criteria ⩾grade 3 according to the NCI CTC guidelines.

Results

In the first stage eight patients were enrolled. Median age was 70years (range 55–76) and ECOG PS 0/1 (%) was 87.5/12.5. Major side effects were mostly intestinal bleeding (grade 3, 25%), diarrhea (grade 3, 25%), perianal and abdominal pain (grades 3 and 4, 25%) followed by anemia (grade 3, 12.5%). Tumor downstaging was observed in 37.5% of patients with complete pathological response in two patients (25%).

Conclusions

After interim analysis of feasibility and tolerability, accrual was terminated according to protocol due to ⩾grade 3 toxicities in 50% of patients. Complete pathological response was seen in 25% of patients but was accompanied by considerable toxicity. Further clinical trials are needed to clarify the role of bevacizumab in this setting.

Keywords: Rectal cancer, Chemoradiation, Capecitabine, Bevacizumab