Phase II study of bevacizumab and chemoradiation in the preoperative or adjuvant treatment of patients with stage II/III rectal cancer.

Abstract

BACKGROUND AND PURPOSE:

We wanted to evaluate the efficacy, defined as 2-year disease-free survival (DFS), and safety of bevacizumab/chemoradiation in preoperative and adjuvant settings for patients with stage II/III rectal cancer.

PATIENTS AND METHODS:

Eligible patients had stage II/III rectal adenocarcinoma, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, and adequate organ function, and received preoperative (cohort A) or adjuvant (cohort B) treatment at physician discretion. Patients received 5-fluorouracil (5-FU) as an intravenous infusion (IVCI) 225 mg/m(2)/d on days 1-42, bevacizumab 5 mg/kg intravenously (I.V.) on days 1 and 15 (cohort A), or every 2 weeks (cohort B), with radiation therapy to 50.4 Gy. After surgery (cohort A) or chemoradiation (cohort B), FOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin) and bevacizumab were administered for 4 months and then bevacizumab was given alone for up to 1 year.

RESULTS:

Sixty-six patients (cohort A = 35; cohort B = 31) were enrolled from August 2006-April 2009: median age was 57 years; male patients, 62%; ECOG PS 0, 75%; stage II/III, 31%/69%. In cohort A, the complete pathologic response (pCR) rate was 29% (11% microscopic residual disease, 49% gross disease). Four patients did not undergo surgery (toxicity, 2 patients; progressive disease, 1 patient; patient decision, 1 patient). One- and 2-year DFS for cohorts A/B were 85%/not reached and 97%/89%, respectively (median survival not reached for either cohort). Frequent grade 3/4 toxicity included diarrhea (A cohort, 14%; B cohort, 29%), neutropenia (A cohort, 14%, B cohort, 23%), mucositis (A cohort, 23%, B cohort, 0%), and fatigue (A cohort, 6%, B cohort, 10%). Other serious toxicity included bowel perforation and pelvic infection (cohort A, 1 patient each), bowel perforation (2 patients), anal wound dehiscence (1 patient), perianal infection (2 patients), and rectovaginal fistula (1 patient) (cohort B), without treatment-related death in either cohort.

CONCLUSIONS:

Bevacizumab can be added to standard preoperative and adjuvant chemoradiation in most patients with expected and manageable toxicity and may increase treatment efficacy.

• Authors: David R Spigel, Johanna C Bendell, Michael McCleod, Dianna L Shipley, Edward Arrowsmith, E Kirk Barnes, Jeffrey R Infante, Howard A Burris 3rd, F Anthony Greco, John D Hainsworth
• Journal: Clinical colorectal cancer (Clin Colorectal Cancer) Vol. 11 Issue 1 Pg. 45-52 (Mar 2012) ISSN: 1938-0674 [Electronic] United States
• PMID: 21840771 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Organoplatinum Compounds
• Oxaliplatin
• Bevacizumab
• Leucovorin
• Fluorouracil

Topics

• Adenocarcinoma (mortality, secondary, therapy)
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab
• Chemoradiotherapy
• Chemotherapy, Adjuvant
• Female
• Fluorouracil (administration & dosage)
• Follow-Up Studies
• Humans
• Leucovorin (administration & dosage)
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Staging
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Preoperative Care
• Rectal Neoplasms (mortality, pathology, therapy)
• Survival Rate
• Treatment Outcome