Skip to main content
Top
Published in: Abdominal Radiology 2/2013

01-04-2013

Bevacizumab-induced perforation of the gastrointestinal tract: clinical and radiographic findings in 11 patients

Authors: Samuel E. Borofsky, Marc S. Levine, Stephen E. Rubesin, Janos L. Tanyi, Christina S. Chu, Anna S. Lev-Toaff

Published in: Abdominal Radiology | Issue 2/2013

Login to get access

Abstract

Aim

To present the gastrointestinal (GI) complications associated with bevacizumab therapy and their findings on abdominal imaging studies.

Methods

A computerized search identified 11 patients with GI complications of bevacizumab therapy on abdominal CT (n = 11) and fluoroscopic GI contrast studies (n = 4) who met our study criteria (including five patients with ovarian cancer, five with colon cancer, and one with cervical cancer). The medical records and imaging studies were reviewed to determine the clinical and radiographic findings in these patients.

Results

All 11 patients had findings of GI perforation on CT, or CT and GI contrast studies. CT revealed a localized extraluminal collection containing gas, fluid, and/or contrast material in eight patients (73%) with focal perforation, and free abdominal air and fluid in three (27%) with free perforation The imaging studies also revealed seven fistulas, including two colovaginal, one rectovaginal, one enterocutaneous, one colocutaneous, one gastrocolic, and one colorectal fistula. Eight (73%) of the 11 patients died within 1 year of the development of GI perforation, and the perforation was felt to be the cause of death in four patients (36%).

Conclusion

Abdominal CT and fluoroscopic GI contrast studies are useful imaging tests for the diagnosis of potentially life-threatening GI perforation as a complication of bevacizumab therapy. When GI perforation is detected on abdominal imaging studies, treatment with bevacizumab should immediately be discontinued.
Literature
1.
go back to reference Horn L, Sandler A (2007) Chemotherapy and antiangiogenic agents in non-small-cell lung cancer. Clin Lung Cancer 8(suppl 2):S68–S73PubMedCrossRef Horn L, Sandler A (2007) Chemotherapy and antiangiogenic agents in non-small-cell lung cancer. Clin Lung Cancer 8(suppl 2):S68–S73PubMedCrossRef
2.
go back to reference Ranieri G, Patruno R, Ruggieri E, et al. (2006) Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic [Review]. Curr Med Chem 13:1845–1857PubMedCrossRef Ranieri G, Patruno R, Ruggieri E, et al. (2006) Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic [Review]. Curr Med Chem 13:1845–1857PubMedCrossRef
3.
go back to reference Homsi J, Daud AI (2007) Spectrum of activity and mechanism of action of VEGF/PDGF inhibitors. Cancer Control 14:285–294PubMed Homsi J, Daud AI (2007) Spectrum of activity and mechanism of action of VEGF/PDGF inhibitors. Cancer Control 14:285–294PubMed
4.
go back to reference Van Cutsem E, Rivera F, Berry S, et al. (2009) Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 20:1842–1847PubMedCrossRef Van Cutsem E, Rivera F, Berry S, et al. (2009) Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 20:1842–1847PubMedCrossRef
5.
go back to reference Hurwitz H, Fehrenbacher L, Novotny W, et al. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342PubMedCrossRef Hurwitz H, Fehrenbacher L, Novotny W, et al. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342PubMedCrossRef
6.
go back to reference Sandler A, Gray R, Perry MC, et al. (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550PubMedCrossRef Sandler A, Gray R, Perry MC, et al. (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550PubMedCrossRef
7.
go back to reference Miller K, Wang M, Gralow J, et al. (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676PubMedCrossRef Miller K, Wang M, Gralow J, et al. (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676PubMedCrossRef
8.
go back to reference Sparano JA, Gray R, Giantonio B, et al. (2004) Evaluating antiangiogenesis agents in the clinic: the eastern cooperative oncology group portfolio of clinical trials. Clin Cancer Res 10:1206–1211PubMedCrossRef Sparano JA, Gray R, Giantonio B, et al. (2004) Evaluating antiangiogenesis agents in the clinic: the eastern cooperative oncology group portfolio of clinical trials. Clin Cancer Res 10:1206–1211PubMedCrossRef
9.
go back to reference Ley EJ, Vukasin P, Kaiser AM, et al. (2007) Delayed rectovaginal fistula: a potential complication of bevacizumab (avastin) [Letter]. Dis Colon Rectum 50:930PubMedCrossRef Ley EJ, Vukasin P, Kaiser AM, et al. (2007) Delayed rectovaginal fistula: a potential complication of bevacizumab (avastin) [Letter]. Dis Colon Rectum 50:930PubMedCrossRef
10.
go back to reference Chéreau E, Stefanescu D, Selle F, et al. (2009) Spontaneous rectovaginal fistula during bevacizumab therapy for ovarian cancer: a case report. Am J Obstet Gynecol 200:e15–e16PubMedCrossRef Chéreau E, Stefanescu D, Selle F, et al. (2009) Spontaneous rectovaginal fistula during bevacizumab therapy for ovarian cancer: a case report. Am J Obstet Gynecol 200:e15–e16PubMedCrossRef
11.
go back to reference Gordon MS, Cunningham D (2005) Managing patients treated with bevacizumab combination therapy. Oncology 69(suppl 3):25–33PubMedCrossRef Gordon MS, Cunningham D (2005) Managing patients treated with bevacizumab combination therapy. Oncology 69(suppl 3):25–33PubMedCrossRef
12.
go back to reference Garcia AA, Hirte H, Fleming G, et al. (2008) Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol 26:76–82PubMedCrossRef Garcia AA, Hirte H, Fleming G, et al. (2008) Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol 26:76–82PubMedCrossRef
13.
go back to reference Badgwell BD, Camp ER, Feig B, et al. (2008) Management of bevacizumab-associated bowel perforation: a case series and review of the literature. Ann Oncol 19:577–582PubMedCrossRef Badgwell BD, Camp ER, Feig B, et al. (2008) Management of bevacizumab-associated bowel perforation: a case series and review of the literature. Ann Oncol 19:577–582PubMedCrossRef
14.
go back to reference Vincenzi B, Santini D, Russo A, et al. (2009) Bevacizumab in association with de gramont 5-fluorouracil/folinic acid in patients with oxaliplatin-, irinotecan-, and cetuximab-refractory colorectal cancer: a single-center phase 2 trial. Cancer 115:4849–4856PubMedCrossRef Vincenzi B, Santini D, Russo A, et al. (2009) Bevacizumab in association with de gramont 5-fluorouracil/folinic acid in patients with oxaliplatin-, irinotecan-, and cetuximab-refractory colorectal cancer: a single-center phase 2 trial. Cancer 115:4849–4856PubMedCrossRef
15.
go back to reference Monk BJ, Sill MW, Burger RA, et al. (2009) Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 27:1069–1074PubMedCrossRef Monk BJ, Sill MW, Burger RA, et al. (2009) Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 27:1069–1074PubMedCrossRef
16.
go back to reference Hapani S, Chu D, Wu S (2009) Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis [Review]. Lancet Oncol 10:559–568PubMedCrossRef Hapani S, Chu D, Wu S (2009) Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis [Review]. Lancet Oncol 10:559–568PubMedCrossRef
17.
go back to reference Cannistra SA, Matulonis UA, Penson RT, et al. (2007) Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 25:5180–5186PubMedCrossRef Cannistra SA, Matulonis UA, Penson RT, et al. (2007) Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 25:5180–5186PubMedCrossRef
18.
go back to reference Wright JD, Hagemann A, Rader JS, et al. (2006) Bevacizumab combination therapy in recurrent, platinum-refractory, epithelial ovarian carcinoma: a retrospective analysis. Cancer 107:83–89PubMedCrossRef Wright JD, Hagemann A, Rader JS, et al. (2006) Bevacizumab combination therapy in recurrent, platinum-refractory, epithelial ovarian carcinoma: a retrospective analysis. Cancer 107:83–89PubMedCrossRef
19.
go back to reference Nimeiri HS, Oza AM, Morgan RJ, et al. (2008) Efficacy and safety of bevacizumab plus erlotinib for patients with recurrent ovarian, primary peritoneal, and fallopian tube cancer: a trial of the Chicago, PMH, and California Phase II Consortia. Gynecol Oncol 110:49–55PubMedCrossRef Nimeiri HS, Oza AM, Morgan RJ, et al. (2008) Efficacy and safety of bevacizumab plus erlotinib for patients with recurrent ovarian, primary peritoneal, and fallopian tube cancer: a trial of the Chicago, PMH, and California Phase II Consortia. Gynecol Oncol 110:49–55PubMedCrossRef
20.
go back to reference Skillings JR, Johnson DH, Miller K, et al. (2005) Arterial thromboembolic events (ATEs) in a pooled analysis of 5 randomized, controlled trials (RCTs) of bevacizumab (BV) with chemotherapy. J Clin Oncol 23(suppl 16):3019 Skillings JR, Johnson DH, Miller K, et al. (2005) Arterial thromboembolic events (ATEs) in a pooled analysis of 5 randomized, controlled trials (RCTs) of bevacizumab (BV) with chemotherapy. J Clin Oncol 23(suppl 16):3019
21.
go back to reference Zangari M, Fink LM, Elice F, et al. (2009) Thrombotic events in patients with cancer receiving antiangiogenesis agents. J Clin Oncol 27:4865–4873PubMedCrossRef Zangari M, Fink LM, Elice F, et al. (2009) Thrombotic events in patients with cancer receiving antiangiogenesis agents. J Clin Oncol 27:4865–4873PubMedCrossRef
22.
go back to reference Scappaticci F, Fehrenbacher L, Cartwright T, et al. (2005) Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91:173–180PubMedCrossRef Scappaticci F, Fehrenbacher L, Cartwright T, et al. (2005) Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91:173–180PubMedCrossRef
23.
go back to reference Goodgame B, Veeramachaneni N, Patterson A, et al. (2008) Tracheo-esophageal fistula with bevacizumab after mediastinal radiation. J Thorac Oncol 3:1080–1081PubMedCrossRef Goodgame B, Veeramachaneni N, Patterson A, et al. (2008) Tracheo-esophageal fistula with bevacizumab after mediastinal radiation. J Thorac Oncol 3:1080–1081PubMedCrossRef
24.
go back to reference Spigel DR, Hainsworth JD, Yardley DA, et al. (2010) Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab. J Clin Oncol 28:43–48PubMedCrossRef Spigel DR, Hainsworth JD, Yardley DA, et al. (2010) Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab. J Clin Oncol 28:43–48PubMedCrossRef
25.
go back to reference Saif MW, Elfiky A, Salem RR (2007) Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol 14:1860–1869PubMedCrossRef Saif MW, Elfiky A, Salem RR (2007) Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol 14:1860–1869PubMedCrossRef
26.
go back to reference Wolf I, Urban D, Pfeffer R, et al. (2007) High incidence of fistula formation during bevacizumab treatment in rectal cancer patients [Letter]. Acta Oncol 46:550–553PubMedCrossRef Wolf I, Urban D, Pfeffer R, et al. (2007) High incidence of fistula formation during bevacizumab treatment in rectal cancer patients [Letter]. Acta Oncol 46:550–553PubMedCrossRef
27.
go back to reference Gressett SM, Shah SR (2009) Intricacies of bevacizumab-induced toxicities and their management. Ann Pharmacother 43:490–501PubMedCrossRef Gressett SM, Shah SR (2009) Intricacies of bevacizumab-induced toxicities and their management. Ann Pharmacother 43:490–501PubMedCrossRef
28.
go back to reference Tarnawski AS (2005) Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 50(suppl 1):S24–S33PubMedCrossRef Tarnawski AS (2005) Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 50(suppl 1):S24–S33PubMedCrossRef
29.
go back to reference Heinzerling JH, Huerta S (2006) Bowel perforation from bevacizumab for the treatment of metastatic colon cancer: incidence, etiology, and management. Curr Surg 63:334–347PubMedCrossRef Heinzerling JH, Huerta S (2006) Bowel perforation from bevacizumab for the treatment of metastatic colon cancer: incidence, etiology, and management. Curr Surg 63:334–347PubMedCrossRef
30.
go back to reference Tol J, Cats A, Mol L, et al. (2008) Gastrointestinal ulceration as a possible side effect of bevacizumab which may herald perforation. Invest New Drugs 26:393–397PubMedCrossRef Tol J, Cats A, Mol L, et al. (2008) Gastrointestinal ulceration as a possible side effect of bevacizumab which may herald perforation. Invest New Drugs 26:393–397PubMedCrossRef
Metadata
Title
Bevacizumab-induced perforation of the gastrointestinal tract: clinical and radiographic findings in 11 patients
Authors
Samuel E. Borofsky
Marc S. Levine
Stephen E. Rubesin
Janos L. Tanyi
Christina S. Chu
Anna S. Lev-Toaff
Publication date
01-04-2013
Publisher
Springer-Verlag
Published in
Abdominal Radiology / Issue 2/2013
Print ISSN: 2366-004X
Electronic ISSN: 2366-0058
DOI
https://doi.org/10.1007/s00261-012-9913-3

Other articles of this Issue 2/2013

Abdominal Radiology 2/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.