Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer.
OBJECTIVE
To study the safety of bevacizumab with capecitabine-based chemoradiotherapy.


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.


CONCLUSIONS
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.
Crane
Christopher H
CH
Department of Radiation Oncology, Unit 97, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. ccrane@mdanderson.org
Ellis
Lee M
LM
Abbruzzese
James L
JL
Amos
Christina
C
Xiong
Henry Q
HQ
Ho
Linus
L
Evans
Douglas B
DB
Tamm
Eric P
EP
Ng
Chaan
C
Pisters
Peter W T
PW
Charnsangavej
Chusilp
C
Delclos
Marc E
ME
O'Reilly
Michael
M
Lee
Jeffrey E
JE
Wolff
Robert A
RA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D000068258:Bevacizumab; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004064:Digestive System / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D016577:Pancreaticoduodenectomy; D010438:Peptic Ulcer Hemorrhage / Q000139:chemically induced; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil