Toxicity study of gemcitabine, oxaliplatin, and bevacizumab, followed by 5-fluorouracil, oxaliplatin, bevacizumab, and radiotherapy, in patients with locally advanced pancreatic cancer.

PURPOSE: Platinum compounds or bevacizumab, in combination with gemcitabine, achieved good response rates in early studies in advanced pancreatic cancer. This prompted an evaluation of an aggressive approach to allow better local control and resectability in locally advanced disease.

METHODS: We piloted a combination of gemcitabine/oxaliplatin/bevacizumab Q2w for four cycles, followed by oxaliplatin and bevacizumab added to infusional 5-FU and radiotherapy, in patients with locally advanced pancreatic cancer.

RESULTS: Nineteen patients were treated, of whom 17 completed the protocol-specified treatment. Median age was 60 years. Fifteen had unresectable, and four had borderline resectable disease. Toxicity of chemotherapy was moderate: grade III neutropenia (5) and grade I/II nausea, vomiting, fatigue, and neuropathy. During chemoradiation, major grade III toxicities were nausea and vomiting (3 each). One patient had intractable pain early on, necessitating treatment cessation. Response rate for 18 evaluable patients was 11 % (by RECIST); five patients (4 inoperable, 1 borderline, 26 %) went on to have surgery. One-year overall survival was 58 % and progression-free survival was 37 %.

CONCLUSIONS: This combination, associated with higher response rates in metastatic disease, had a lower than expected response rate in primary tumors. Although tolerable, our approach failed to affect clinical outcomes meaningfully.