Cancer Res Treat.  2008 Mar;40(1):33-35.

Intestinal Perforation in Colorectal Cancers Treated with Bevacizumab (Avastin(R))

• Choi YI
• Lee SH
• Ahn BK
• Baek SU
• Park SJ
• Kim YS
• Shin SH

Abstract

Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), and it has shown promise as a clinical agent against metastatic colorectal cancer, and particularly in combination with chemotherapy. Bowel perforation is a known risk that's associated with bevacizumab use, but the etiology is unknown. Here we report on two cases of metastatic colorectal cancer in which the patients suffered from intestinal perforation after chemotherapy with bevacizumab. For the first case, a 47 year-old man had rectal cancer with concurrent liver and lung metastasis. He underwent chmotherapy with 5-fluorouracil, irinotecan and bevacizumab. Fever and abdominal pain developed seven days later, and rectal perforation was identified upon exploration 13 days later. For the second case, a 48 year-old woman had sigmoid colon cancer with peritoneal and ovary metastases. After seven days of chemotherapy with 5-fluorouracil, oxaliplatin and bevacizumab, exploratory surgery revealed a perforation at the ileum.

Keyword

Bevacizumab; Intestinal perforation; Colorectal neoplasms

MeSH Terms

Abdominal Pain
Antibodies, Monoclonal, Humanized
Camptothecin
Colorectal Neoplasms
Female
Fever
Fluorouracil
Humans
Ileum
Intestinal Perforation
Liver
Lung
Neoplasm Metastasis
Organoplatinum Compounds
Ovary
Rectal Neoplasms
Sigmoid Neoplasms
Vascular Endothelial Growth Factor A
Bevacizumab
Antibodies, Monoclonal, Humanized
Camptothecin
Fluorouracil
Organoplatinum Compounds
Vascular Endothelial Growth Factor A

Figure

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  Fig. 1 Operation findings. Rectal perforation was identified at the sacral promontory level, which was the primary tumor site in case 1.

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  Fig. 2 Operation findings. An ileal perforation was identified in case 2. The proximal intestine was moderate distended and it showed wall thickening.

Reference

1. Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997; 57:4593–4599. PMID: 9377574.

2. Kabbinavar F, Hurwitz H, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol. 2003; 21:60–65. PMID: 12506171.

3. Chen HX, Mooney M, Boron M, Vena D, Mosby K, Grochow L, et al. Phase II multicenter trial of bevacizumab plus fluorouracil and leucovorin in patients with advanced refractory colorectal cancer: an NCI Treatment Referral Center Trial TRC-0301. J Clin Oncol. 2006; 24:3354–3360. PMID: 16849749.

4. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350:2335–2342. PMID: 15175435.

5. Scappaticci FA, Fehrenbacher L, Cartwright T, Hainsworth JD, Heim W, Berlin J, et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol. 2005; 91:173–180. PMID: 16118771.

6. Gordon MS, Cunningham D. Managing patients treated with bevacizumab combination therapy. Oncology. 2005; 69(suppl 3):25–33. PMID: 16301833.

7. Lordick F, Geinitz H, Theisen J, Sendler A, Sarbia M. Increased risk of ischemic bowel complications during treatment with bevacizumab after pelvic irradiation: report of three cases. Int J Radiat Oncol Biol Phys. 2006; 64:1295–1298. PMID: 16503384.

8. Saif MW, Elfiky A, Salem RR. Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol. 2007; 14:1860–1869. PMID: 17356952.

9. Han ES, Monk BJ. What is the risk of bowel perforation associated with bevacizumab therapy in ovarian cancer? Gynecol Oncol. 2007; 105:3–6. PMID: 17383545.

10. Heinzerling JH, Huerta S. Bowel perforation from bevacizumab for the treatment of metastatic colon cancer: incidence, etiology, and management. Curr Surg. 2006; 63:334–337. PMID: 16971205.