medwireNews: The addition of bevacizumab and oxaliplatin to standard neoadjuvant chemoradiotherapy does not enhance clinical response rates in rectal cancer, show phase II study results.
Furthermore, supplementation of the two drugs led to significant rates of toxicity and complications among patients.
"The addition of oxaliplatin and bevacizumab to standard neoadjuvant [chemoradiotherapy] did not achieve the expected pathologic [clinical response] rate of 30%," say Jerome Landry (Emory University, Atlanta, Georgia, USA) and colleagues.
Fifty-four patients with T3 or T4 nonmetastatic disease took part in the trial. They received standard preoperative chemoradiotherapy with capecitabine supplemented with oxaliplatin 50 mg/m2 on days 1, 8, 15, 22, and 29 of radiotherapy, and bevacizumab 5 mg/kg on days 1, 15 and 29 of radiotherapy.
Following surgery, patients received 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), supplemented with bevacizumab 5 mg/kg every 2 weeks over 12 cycles.
Only 17% of patients achieved pathologic clinical remission. However, 59% experienced pathologic tumor downstaging, and of the 32 patients with nodal involvement, 21 experienced nodal downstaging.
The authors noted considerable toxicity among patients, including two deaths, one of which was attributed to the study therapy. Fifty-three percent of patients experienced grade 3 toxicity at worst, and 15% experienced grade 4 toxicity at worst, during preoperative therapy.
Late surgical complications, after hospital discharge, were also common, occurring in 47% of patients. The most common of these were wound infection and wound/fascia dehiscence.
Notably, only 30% of patients completed the entire treatment according to the trial protocol.
The authors explain in Cancer that their trial began prior to the results of several phase III studies reporting the effect of the addition of oxaliplatin to fluoropyrimidine-based neoadjuvant chemoradiotherapy. These have largely shown no benefit, and furthermore, led to increased toxicity compared with standard regimens.
They add that they will follow up patients to establish the long-term morbidity and mortality of the regimen.
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