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Phase I Trial Evaluating the Safety of Bevacizumab With Concurrent Radiotherapy and Capecitabine in Locally Advanced Pancreatic Cancer

From the Departments of Radiation Oncology, Cancer Biology, Gastrointestinal Medical Oncology, Diagnostic Imaging, and Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and the Pancreatic Tumor Study Group

Address reprint requests to Christopher H. Crane, MD, Department of Radiation Oncology, Unit 97, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: ccrane{at}mdanderson.org

PURPOSE: To study the safety of bevacizumab with capecitabine-based chemoradiotherapy.

PATIENTS AND METHODS: Patients with inoperable pancreatic adenocarcinoma received bevacizumab 2 weeks before radiotherapy (50.4 Gy treating the primary tumor and gross adenopathy), every 2 weeks during radiotherapy (12 patients each at 2.5, 5.0, 7.5, and 10 mg/kg), and after radiotherapy until disease progression. Capecitabine was administered on days 14 through 52 (650 mg/m² orally twice daily for the first six patients; 825 mg/m² for the remaining patients).

RESULTS: Significant acute gastrointestinal (43% grade 2; 4% grade 3), hand and foot syndrome (21% grade 2), and transient hematologic (8% grade 3 or greater) events were uncommon with protocol mandated dose reductions of capecitabine grade 2 toxicity (43% of patients). Among the first 30 patients treated, three patients had tumor-associated bleeding duodenal ulcers, and one had a contained duodenal perforation. No additional bleeding events occurred among the final 18 patients after patients with duodenal involvement by tumor were excluded. Nine (20%) of 46 assessable patients had confirmed partial responses until distant progression for a median of 6.2 months. Four patients have undergone pancreaticoduodenectomy without perioperative complication. The median survival was 11.6 months (95% CI, 9.6 to 13.6), from the start of protocol therapy.

CONCLUSION: Concurrent bevacizumab did not significantly increase the acute toxicity of a relatively well-tolerated chemoradiotherapy regimen. However, ulceration and bleeding in the radiation field possibly related to bevacizumab occurred when tumor involved the duodenal mucosa. The encouraging efficacy end points suggest that the further study of bevacizumab with chemoradiotherapy is warranted.

Supported by Grant Nos. CA06294 and CA16672 from the National Cancer Institute, Department of Health and Human Services, and Genentech, Inc.

Presented at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005.

This material has not been previously published in manuscript form.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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