TY - JOUR
T1 - Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer
AU - Crane, Christopher H.
AU - Ellis, Lee M.
AU - Abbruzzese, James L.
AU - Amos, Christina
AU - Xiong, Henry Q.
AU - Ho, Linus
AU - Evans, Douglas B.
AU - Tamm, Eric P.
AU - Ng, Chaan
AU - Pisters, Peter W.T.
AU - Charnsangavej, Chusilp
AU - Delclos, Marc E.
AU - O'Reilly, Michael
AU - Lee, Jeffrey E.
AU - Wolff, Robert A.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2006/3/1
Y1 - 2006/3/1
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2005.03.6780
DO - 10.1200/JCO.2005.03.6780
M3 - Article
C2 - 16505434
AN - SCOPUS:33644968548
SN - 0732-183X
VL - 24
SP - 1145
EP - 1151
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 7
ER -