Faculty Collaboration Database

Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer. J Clin Oncol 2006 Mar 01;24(7):1145-51

Date

03/01/2006

Pubmed ID

16505434

DOI

10.1200/JCO.2005.03.6780

Scopus ID

2-s2.0-33644968548 (requires institutional sign-in at Scopus site)   197 Citations

Abstract

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.

Author List

Crane CH, Ellis LM, Abbruzzese JL, Amos C, Xiong HQ, Ho L, Evans DB, Tamm EP, Ng C, Pisters PW, Charnsangavej C, Delclos ME, O'Reilly M, Lee JE, Wolff RA

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antimetabolites, Antineoplastic
Antineoplastic Combined Chemotherapy Protocols
Bevacizumab
Capecitabine
Chemotherapy, Adjuvant
Deoxycytidine
Digestive System
Drug Administration Schedule
Female
Fluorouracil
Humans
Male
Middle Aged
Neoplasm Staging
Pancreatic Neoplasms
Pancreaticoduodenectomy
Peptic Ulcer Hemorrhage
Radiotherapy, Adjuvant
Treatment Outcome