Gastrointestinal perforation in metastatic colorectal cancer patients with peritoneal metastases receiving bevacizumab.

Abstract

AIM:

To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease.

METHODS:

We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts: (1) the AGITG MAX trial (Phase III randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine, bevacizumab and mitomycinC); (2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (any first-line regimen ± bevacizumab); and (3) two cancer centres in New South Wales, Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre (NSWCC) from January 2005 to Decenber 2012, (any first-line regimen ± bevacizumab). For the AGITG MAX trial capecitabine was compared to the other two arms (capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycinC). In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases. Secondary endpoints included progression-free survival, chemotherapy duration, and overall survival. Time-to-event outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test.

RESULTS:

Eighty-four MAX, 179 TRACC and 69 NSWCC patients had peritoneal disease. There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts. Of the patients without peritoneal disease in the MAX trial, 4/300 (1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123 (0.8%) in the capecitabine alone arm. In the TRACC registry 3/126 (2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53 (1.9%) in the chemotherapy alone arm. In a further analysis of patients without peritoneal metastases in the TRACC registry, the rate of gastrointestinal perforations was 9/369 (2.4%) in the chemotherapy/bevacizumab group and 5/177 (2.8%) in the chemotherapy alone group. The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts: MAX 6.9 m vs 4.9 m, HR = 0.64 (95%CI: 0.42-1.02); P = 0.063; TRACC 9.1 m vs 5.5 m, HR = 0.61 (95%CI: 0.37-0.86); P = 0.009; NSWCC 8.7 m vs 6.8 m, HR = 0.75 (95%CI: 0.43-1.32); P = 0.32. Chemotherapy duration was similar across the groups.

CONCLUSION:

Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone.

• Authors: Aflah Roohullah, Hui-Li Wong, Katrin M Sjoquist, Peter Gibbs, Kathryn Field, Ben Tran, Jeremy Shapiro, Joe Mckendrick, Desmond Yip, Louise Nott, Val Gebski, Weng Ng, Wei Chua, Timothy Price, Niall Tebbutt, Lorraine Chantrill
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 21 Issue 17 Pg. 5352-8 (May 07 2015) ISSN: 2219-2840 [Electronic] United States
• PMID: 25954110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Bevacizumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors (adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Bevacizumab (adverse effects)
• Clinical Trials, Phase III as Topic
• Colorectal Neoplasms (drug therapy, mortality, pathology)
• Disease Progression
• Disease-Free Survival
• Female
• Humans
• Intestinal Perforation (chemically induced, diagnosis)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Peritoneal Neoplasms (drug therapy, mortality, secondary)
• Randomized Controlled Trials as Topic
• Registries
• Risk Assessment
• Risk Factors
• Time Factors
• Treatment Outcome
• Young Adult