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Investigational New Drugs
Published in: Investigational New Drugs 4/2008

Open Access 01-08-2008 | PHASE III STUDIES

Gastrointestinal ulceration as a possible side effect of bevacizumab which may herald perforation

Authors: J. Tol, A. Cats, L. Mol, M. Koopman, M. M. E. M. Bos, J. J. M. van der Hoeven, N. F. Antonini, J. H. J. M. van Krieken, C. J. A. Punt

Published in: Investigational New Drugs | Issue 4/2008

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Summary

Chemotherapy plus bevacizumab is currently considered as the standard 1st line treatment of advanced colorectal cancer (ACC). Whereas GI perforation is a known side effect of bevacizumab, the development of GI ulcers has not been reported. We identified 18 patients with ACC who participated in a phase III multicentre trial which included chemotherapy and bevacizumab, who developed a GI ulcer (n = 6), perforation (n = 8) or both (n = 4). The risk of developing a symptomatic GI ulcer or perforation was 1.3% and 1.6%, respectively. Central review of the histology specimens showed ulceration and/or granulation tissue with neovascularisation. The majority (89%) of events developed early during treatment. Given these observations, as well as the relationship between VEGF and mucosal injury healing, we suggest that GI ulcers may occur as a side effect of treatment with bevacizumab and may herald perforation.
Literature
1.
Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW (2005) Colorectal cancer. Lancet 365(9454):153–165PubMedCrossRef
2.
Punt CJ (2004) New options and old dilemmas in the treatment of patients with advanced colorectal cancer. Ann Oncol 15(10):1453–1459PubMedCrossRef
3.
Tol J, Punt CJA (2007) Targeted therapy in advanced colorectal cancer, an update. Targeted Oncology 2(3):165–172 July 2007CrossRef
4.
Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9(6):669–676PubMedCrossRef
5.
Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S (2005) Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol 23(16):3706–3712PubMedCrossRef
6.
Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342PubMedCrossRef
7.
Giantonio BJ, Catalano PJ, Meropol NJ et al (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25(12):1539–1544PubMedCrossRef
8.
Saif MW, Elfiky A, Salem RR (2007) Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol 14(6):1860–1869PubMedCrossRef
9.
Kretzschmar A, Cunningham D, Berry S et al (2006) Incidence of gastrointestinal perforations and bleeding in patients starting bevacizumab treatment in first-line metastatic CRC without primary tumour resection—preliminary results from BEAT [abstract 248]. Proc Am Soc Clin Oncol GI 209
10.
Shah MA, Ramanathan RK, Ilson DH et al (2006) Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol 24(33):5201–5206PubMedCrossRef
11.
Kindler HL, Friberg G, Singh DA et al (2005) Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 23(31):8033–8040PubMedCrossRef
12.
Han ES, Monk BJ (2007) What is the risk of bowel perforation associated with bevacizumab therapy in ovarian cancer? Gynecol Oncol 105(1):3–6PubMedCrossRef
13.
Sugrue M, Kozloff M, Hainsworth J et al (2006) Risk factors for gastrointestinal perforations in patients with metastatic colorectal cancer receiving bevacizumab plus chemotherapy [abstract 3535]. Proc Am Soc Clin Oncol 24:154S
14.
Tol J, Koopman M, Rodenburg CJ et al (2008) A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO 2 study of the Dutch Colorectal Cancer Group (DCCG). An interim anaylsis of toxicity. Ann Oncol Feb 13 (in press)
15.
Garcia Rodriguez LA, Hernandez-Diaz S (2004) Risk of uncomplicated peptic ulcer among users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Am J Epidemiol 159(1):23–31PubMedCrossRef
16.
Tarnawski AS (2005) Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 50(Suppl 1):S24–S33PubMedCrossRef
17.
Gyires K (2005) Gastric mucosal protection: from prostaglandins to gene-therapy. Curr Med Chem 12(2):203–215PubMed
18.
Malara B, Josko J, Tyrpien M, Malara P, Steplewska K (2005) Dynamics of changes in vascular endothelial growth factor (VEGF) expression and angiogenesis in stress-induced gastric ulceration in rats. J Physiol Pharmacol 56(2):259–271PubMed
19.
Yoshida M, Wakabayashi G, Ishikawa H et al (2003) A possible defensive mechanism in the basal region of gastric mucosa and the healing of erosions. Clin Hemorheol Microcirc 29(3–4):301–312PubMed
20.
Thornton AD, Ravn P, Winslet M, Chester K (2006) Angiogenesis inhibition with bevacizumab and the surgical management of colorectal cancer. Br J Surg 93(12):1456–1463PubMedCrossRef
21.
Mir O, Mouthon L, Alexandre J et al (2007) Bevacizumab-induced cardiovascular events: a consequence of cholesterol emboli syndrome? J Natl Cancer Inst 99(1):85–86PubMedCrossRef
22.
Buchman AL, Schwartz MR (1996) Colonic ulceration associated with the systemic use of nonsteroidal antiinflammatory medication. J Clin Gastroenterol 22(3):224–226PubMedCrossRef
Metadata
Title
Gastrointestinal ulceration as a possible side effect of bevacizumab which may herald perforation
Authors
J. Tol
A. Cats
L. Mol
M. Koopman
M. M. E. M. Bos
J. J. M. van der Hoeven
N. F. Antonini
J. H. J. M. van Krieken
C. J. A. Punt
Publication date
01-08-2008
Publisher
Springer US
Published in
Investigational New Drugs / Issue 4/2008
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-008-9125-4

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