title: Bevacizumab combined with capecitabine and oxaliplatin in patients with advanced adenocarcinoma of the small bowel or ampulla of vater: A single-center, open-label, phase 2 study.
abstract: BACKGROUND
  Capecitabine with oxaliplatin (CAPOX) has previously demonstrated clinical activity in patients with small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Herein, the authors conducted a phase 2 trial to evaluate the benefit of adding bevacizumab to CAPOX.
  
  
  METHODS
  In this phase 2, single-arm, single-center, open-label study, patients aged ≥18 years with untreated, advanced SBA or AAC were recruited. Patients received capecitabine at a dose of 750 mg/m2orally twice daily on days 1 to 14, oxaliplatin at a dose of 130 mg/m2intravenously on day 1, and bevacizumab at a dose of 7.5 mg/kg intravenously on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary objectives included response rate, overall PFS, overall survival, and toxicity.
  
  
  RESULTS
  Between August 2011 and November 2014, a total of 30 patients were enrolled into the study (male/female ratio of 13/17; median age of 63 years [range, 33-78 years]; and 7 patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 0, 20 patients with an ECOG PS of 1, and 3 patients with an ECOG PS of 2). Of the 30 patients, 23 (77%) had SBA (18 of duodenal origin and 5 of jejunal/ileal origin) and 7 patients (23%) had AAC (5 of pancreaticobiliary subtype, 1 of mixed subtype, and 1 of intestinal subtype). The most common grade 3 toxicities observed were fatigue and hypertension (7 patients each [23%]), neutropenia (6 patients [20%]), and diarrhea (3 patients [10%]) (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). The probability of PFS at 6 months was 68% (95% confidence interval [95% CI], 52% to 88%). The response rate was 48.3%, with 1 complete response and 13 partial responses; 10 patients achieved stable disease. At a median follow-up of 25.9 months, the median PFS was 8.7 months (95% CI, 4.9-10.5 months) and the median overall survival was 12.9 months (95% CI, 9.2-19.7 months).
  
  
  CONCLUSIONS
  The results of the current study indicate that CAPOX with bevacizumab is an active and well-tolerated regimen for patients with SBA and AAC. These findings support the need for further investigation into the clinical benefit of targeting angiogenesis in patients with SBA and AAC. Cancer 2017;123:1011-17. © 2016 American Cancer Society.
authors.affiliation: Hematology/Oncology Fellowship Program, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Pat
authors.initials: P
authors.lastname: Gulhati
authors.affiliation: Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Kanwal
authors.initials: K
authors.lastname: Raghav
authors.affiliation: Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rachna T
authors.initials: RT
authors.lastname: Shroff
authors.affiliation: Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gauri R
authors.initials: GR
authors.lastname: Varadhachary
authors.affiliation: Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Scott
authors.initials: S
authors.lastname: Kopetz
authors.affiliation: Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Milind
authors.initials: M
authors.lastname: Javle
authors.affiliation: Department of Biostatistics and Applied Mathematics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Wei
authors.initials: W
authors.lastname: Qiao
authors.affiliation: Department of Biostatistics and Applied Mathematics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biostatistics and Applied Mathematics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Morris
authors.affiliation: Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.affiliation: Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Overman
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D014670:Ampulla of Vater / Q000473:pathology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D000069287:Capecitabine / Q000008:administration & dosage; D003138:Common Bile Duct Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015897:Comorbidity; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000069287:Capecitabine
keywords: ampullary adenocarcinoma; bevacizumab; capecitabine with oxaliplatin (CAPOX); small bowel adenocarcinoma; small bowel cancer