Phase II Trial of Bevacizumab in Combination with Weekly Docetaxel in Metastatic Breast Cancer Patients

Abstract

Purpose: To evaluate the safety and efficacy of bevacizumab and weekly docetaxel as first-or second-line therapy in patients with metastatic breast cancer (MBC). Patients and Methods: Twenty-seven MBC patients received i.v. bevacizumab at 10 mg/kg on days 1and 15 in combination with i.v. docetaxel 35 mg/m 2 on days 1, 8, and 15 of a 28-day cycle. Primary end points were to assess toxicity, overall response rate, and progression-free survival. A secondary end point was to assess the relationship between plasma endothelial and cell adhesion markers and clinical outcomes. Results: One-hundred fifty-eight treatment cycles were administered with a median of six cycles (range 1-15 cycles) per patient. The most common grade 4 toxicities per patient were as follows: 2 (7%)öpulmonary embolus, 1 (4%)öfebrile neutropenia, and 1 (4%)öinfection; grade 3 toxicities were 4 (15 %)öneutropenia, 4 (15 %)öfatigue, 2 (7 %)öneuropathy, 2 (7%)öathralgias, 2 (7%)östomatitis, 1 (7%)öpleural effusion, and 1 (4%)öhypertension. The overall response rate was 52% [95% confidence interval (95% CI), 32-71%], median response duration was 6.0 months (95% CI, 4.6-6.5 months), and the median progression-free survival was 7.5 months (95% CI, 6.2-8.3 months). In hypothesis-generating univariate and limited multivariate analyses, E-selectin was statistically significantly associated with response to the combination. Conclusion: Bevazicumab in combination with weekly docetaxel is active with acceptable toxicities in MBC. Additional studies evaluating E-selectin as a marker of response to bevacizumabcontaining chemotherapy are warranted.

Identification of TNF-α and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array

“…SDF-1 was suggested by previous studies as a target for renal carcinoma therapy (Reckamp et al, 2008), and increased levels of this cytokine have been shown in sunitinib-treated mice (Ebos et al, 2007). ICAM-1 levels were also checked for validation, because plasma levels of this cytokine have been associated with a response to the anti-VEGF targeting agent bevacizumab in combination with docetaxel in metastatic breast cancer (Ramaswamy et al, 2006). Vascular endothelial growth factor (VEGF) was quantified as well, because its receptors are primary targets of sunitinib.…”

Vascular endothelial growth factor-A stimulates Snail expression in breast tumor cells: Implications for tumor progression

“…Avastin ® (Genentech) is a VEGF-neutralizing antibody that, when used in combination with chemotherapy, prolongs the progression-free survival of breast cancer patients [19,20], presumably due to its ability to suppress tumor angiogenesis [21]. Based on this activity, Avastin ® was recently approved as a therapy for patients with HER2-negative metastatic breast tumors.…”

Bevacizumab

“…In MBC, a single-arm, phase II study of bevacizumab in combination with docetaxel and trastuzumab showed a PFS interval of 7.5 months (95% confidence interval [CI], 6.2-8.3 months) [22]. In other preliminary reports, the combination of bevacizumab (10 mg/kg every 2 weeks) with trastuzumab in human epidermal growth factor receptor 2-positive MBC patients appeared to be well tolerated, with few grade 3 or 4 side effects [23].…”