Randomized Phase II Evaluation of Bevacizumab Versus Bevacizumab Plus Fosbretabulin in Recurrent Ovarian, Tubal, or Peritoneal Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study
| Autor: | Robert L. Coleman, Lainie P. Martin, Jeanne M. Schilder, Bradley J. Monk, Gregory P. Sutton, Krishnansu S. Tewari, Jai Balkissoon, Joan L. Walker, Carol Aghajanian, Michael W. Sill, Christopher J. Darus |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Adult Cancer Research medicine.medical_specialty Randomization Bevacizumab medicine.medical_treatment Gynecologic oncology Revascularization 03 medical and health sciences Peritoneal Neoplasm 0302 clinical medicine Internal medicine Antineoplastic Combined Chemotherapy Protocols Stilbenes Clinical endpoint Medicine Fallopian Tube Neoplasms Humans Peritoneal Neoplasms Aged Aged 80 and over Ovarian Neoplasms Fosbretabulin Tromethamine business.industry ORIGINAL REPORTS Middle Aged 030104 developmental biology 030220 oncology & carcinogenesis Toxicity Female Neoplasm Recurrence Local business medicine.drug |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 34(19) |
| ISSN: | 1527-7755 |
| Popis: | Purpose The vascular disrupting agent fosbretabulin tromethamine selectively targets pre-existing tumor vasculature, which causes vascular shutdown and leads to cancer cell death and necrosis. Antiangiogenesis agents such as bevacizumab, a humanized antivascular endothelial growth factor monoclonal antibody, might prevent revascularization during and after treatment with a vascular disrupting agent. Patients and Methods Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to bevacizumab (15 mg/kg intravenously once every 3 weeks) or the combination of bevacizumab (15 mg/kg) plus fosbretabulin (60 mg/m2) intravenously once every 3 weeks until disease progression or toxicity. Randomization was stratified by disease status (measurable v nonmeasurable), prior bevacizumab, and platinum-free interval. The primary end point was progression-free survival (PFS). The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%. Results The study enrolled 107 patients. Median PFS was 4.8 months for bevacizumab and 7.3 months for bevacizumab plus fosbretabulin (hazard ratio, 0.69; 90% two-sided CI, 0.47 to 1.00; one-sided P = .05). The proportion responding (overall response rate) to bevacizumab was 28.2% among 39 patients with measurable disease and 35.7% among 42 patients treated with the combination. The relative probability of responding was 1.27 (90% CI, 0.74 to 2.17; one-sided P = .24). Adverse events greater than grade 3 were more common in the combination regimen than in bevacizumab only for hypertension (35% v 20%). There was one grade 3 thromboembolic event in the combination arm and one intestinal fistula in the bevacizumab only arm. Conclusion On the basis of the PFS, overall response rate, and tolerability of these two antivascular therapies, further evaluation is warranted for this chemotherapy-free regimen. Fosbretabulin in combination with bevacizumab increases the risk of hypertension. |
| Databáze: | OpenAIRE |
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