Bevacizumab is a recombinant humanized monoclonal antibody that targets the vascular endothelial growth factor (VEGF). VEGF plays an important role in tumor angiogenesis and is overexpressed in a wide range of malignant tumors. Bevacizumab inhibits tumor angiogenesis, targeting both tumor growth and metastasis. Inhibition of VEGF reduces growth of new tumors supplied by vessels, and leads to ‘normalization’ of existing tumor vessels. Therefore, reducing the interstitial fluid pressure should result in an enhanced efficacy of chemotherapeutic drugs.
Bevacizumab is widely used to treat a variety of advanced solid tumors, including colorectal cancer, non-small cell lung cancer, breast cancer, and renal cell cancer (RCC). It has been shown to improve progression-free survival (PFS) in patients with RCC and has been demonstrated to have clinically significant benefits as a first-line treatment for non-small cell lung cancer and breast cancer in combination with cytotoxic agents. In E2100, a significant increase in PFS was observed in patients receiving bevacizumab plus paclitaxel compared with paclitaxel alone [hazard ratio (HR) 0.42; p < 0.0001]. Median PFS was 11.4 versus 5.8 months, respectively. Median overall survival (OS) was 26.5 months with bevacizumab plus paclitaxel versus 24.8 months with paclitaxel alone; the HR for OS was 0.869 (p = 0.1374). The objective response rate more than doubled with the addition of bevacizumab, from 22 to 50%. In E2100, AVADO, and both cohorts of RIBBON-1, PFS was significantly superior in the bevacizumab-containing arm compared with chemotherapy alone, thus meeting the primary objective of each trial. Median PFS was approximately 9–11 months in all four bevacizumab-containing arms [1
]. The response rate with bevacizumab in combination with taxane was 50–64%. The response rate was 35% in the bevacizumab-capecitabine cohort of RIBBON-1 [1
]. Median OS was 26.7 months in the bevacizumab arm compared with 26.4 months in the non-bevacizumab arm. There was no significant difference in OS between the two arms (HR 0.97). The 1-year OS rate was 82% in the bevacizumab-containing arm versus 77% in the non-bevacizumab arm (p = 0.003) [2
]. Bevacizumab has been approved for the treatment of glioblastoma multiforme and RCC. Many trials are currently underway evaluating its efficacy in various kinds of solid tumors [2
]. The adverse effects of bevacizumab are hemorrhage/79.2% (grade 3, 1.7%; grade 4, 0.8%); gastrointestinal tract perforation/0.6% (grade 4, 0.6%), wound dehiscence/5.0%, arterial and venous thromboembolism/0.8%, hypertension/51.7% (grade 3, 16.7%), reversible posterior leukoencephalopathy/0.5%, neutropenia/75.8% (grade 3, 31.7%; grade 4, 10.8%), proteinuria/59.2%, and congestive heart failure/1.7% [2
]. Serous hemorrhage and thrombosis could be lethal. In Japan, this drug was approved in November 2011; since then, an increasing number of patients have been treated with it.
We report an apparently rare case with diverticular bleeding of the colon during chemotherapy with bevacizumab and paclitaxel for recurrent breast cancer.