C F Verschraegen1, H Arias-Pulido2, S-J Lee2, S Movva2, L A Cerilli3, S Eberhardt4, B Schmit4, R Quinn5, C Y Muller5, I Rabinowitz2, M Purdy6, D Snyder6, T Bocklage3. 1. Departments of Hematology/Oncology. Electronic address: claire.verschraegen@vtmednet.org. 2. Departments of Hematology/Oncology. 3. Departments of Pathology. 4. Departments of Radiology. 5. Departments of Surgery, The University of New Mexico Cancer Center, Albuquerque. 6. Department of Oncology, New Mexico Cancer Care Alliance, Albuquerque, USA.
Abstract
BACKGROUND: To assess the response of patients with soft tissue sarcoma (STS) to the combination of docetaxel, bevacizumab, and gemcitabine. Vascular endothelial growth factor (VEGF)-A levels and expression of VEGF-A and VEGF receptors 1 and 2 were evaluated. PATIENTS AND METHODS: Thirty-eight chemotherapy-naive patients with STS were enrolled. A dose-finding study for gemcitabine from 1000, 1250, then 1500 mg/m(2) was done in nine patients (three cohorts), followed by an expansion cohort of 27 patients. Dose of docetaxel was 50 mg/m(2), bevacizumab was 5 mg/kg, and gemcitabine was 1500 mg/m(2), every 2 weeks. Serum VEGF-A was measured by enzyme-linked immunosorbent assay and tissue VEGF-A and its receptors by immunohistochemistry. RESULTS: The median follow-up was 36 months. The overall response rate observed was 31.4%, with 5 complete and 6 partial responses, and 18 stable diseases lasting for a median of 6 months. There was no significant hematologic toxicity. The adverse events with the highest grade were attributed to bevacizumab. There was no correlation of VEGF pathway biomarkers with outcome. CONCLUSIONS: The combination of gemcitabine, docetaxel, and bevacizumab is safe and effective in patients with STS. The most concerning adverse events were consequences of bevacizumab administration. The benefit of bevacizumab in this patient population remains unclear.
BACKGROUND: To assess the response of patients with soft tissue sarcoma (STS) to the combination of docetaxel, bevacizumab, and gemcitabine. Vascular endothelial growth factor (VEGF)-A levels and expression of VEGF-A and VEGF receptors 1 and 2 were evaluated. PATIENTS AND METHODS: Thirty-eight chemotherapy-naive patients with STS were enrolled. A dose-finding study for gemcitabine from 1000, 1250, then 1500 mg/m(2) was done in nine patients (three cohorts), followed by an expansion cohort of 27 patients. Dose of docetaxel was 50 mg/m(2), bevacizumab was 5 mg/kg, and gemcitabine was 1500 mg/m(2), every 2 weeks. Serum VEGF-A was measured by enzyme-linked immunosorbent assay and tissue VEGF-A and its receptors by immunohistochemistry. RESULTS: The median follow-up was 36 months. The overall response rate observed was 31.4%, with 5 complete and 6 partial responses, and 18 stable diseases lasting for a median of 6 months. There was no significant hematologic toxicity. The adverse events with the highest grade were attributed to bevacizumab. There was no correlation of VEGF pathway biomarkers with outcome. CONCLUSIONS: The combination of gemcitabine, docetaxel, and bevacizumab is safe and effective in patients with STS. The most concerning adverse events were consequences of bevacizumab administration. The benefit of bevacizumab in this patient population remains unclear.
Authors: Martee L Hensley; Austin Miller; David M O'Malley; Robert S Mannel; Kian Behbakht; Jamie N Bakkum-Gamez; Helen Michael Journal: J Clin Oncol Date: 2015-02-23 Impact factor: 44.544
Authors: Juan Martín Liberal; Laura Lagares-Tena; Miguel Sáinz-Jaspeado; Silvia Mateo-Lozano; Xavier García Del Muro; Oscar M Tirado Journal: Sarcoma Date: 2012-06-03