Randomized, Double-Blind, Placebo-Controlled Phase II Study of AMG 386 Combined With Weekly Paclitaxel in Patients With Recurrent Ovarian Cancerстатья из журнала
Аннотация: To estimate the efficacy and toxicity of AMG 386, an investigational peptide-Fc fusion protein that neutralizes the interaction between the Tie2 receptor and angiopoietin-1/2, plus weekly paclitaxel in patients with recurrent ovarian cancer.Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned 1:1:1 to receive paclitaxel (80 mg/m(2) once weekly [QW], 3 weeks on/1 week off) plus intravenous AMG 386 10 mg/kg QW (arm A), AMG 386 3 mg/kg QW (arm B), or placebo QW (arm C). The primary end point was progression-free survival (PFS). Secondary end points included overall survival, objective response, CA-125 response, safety, and pharmacokinetics.One hundred sixty-one patients were randomly assigned. Median PFS was 7.2 months (95% CI, 5.3 to 8.1 months) in arm A, 5.7 months (95% CI, 4.6 to 8.0 months) in arm B, and 4.6 months (95% CI, 1.9 to 6.7 months) in arm C. The hazard ratio for arms A and B combined versus arm C was 0.76 (95% CI, 0.52 to 1.12; P = .165). Further analyses suggested an exploratory dose-response effect for PFS across arms (Tarone's test, P = .037). Objective response rates for arms A, B, and C were 37%, 19%, and 27%, respectively. The incidence of grade ≥ 3 adverse events (AEs) in arms A, B, and C was 65%, 55%, and 64%, respectively. Frequent AEs included hypertension (8%, 6%, and 5% in arms A, B, and C, respectively), peripheral edema (71%, 51%, and 22% in arms A, B, and C, respectively), and hypokalemia (21%, 15%, and 5% in arms A, B, and C, respectively). AMG 386 exhibited linear pharmacokinetic properties at the tested doses.AMG 386 combined with weekly paclitaxel was tolerable, with a manageable and distinct toxicity profile. The data suggest evidence of antitumor activity and a dose-response effect, warranting further studies in ovarian cancer.
Год издания: 2011
Авторы: Beth Y. Karlan, Amit M. Oza, Gary Richardson, Diane Provencher, Vincent Hansen, Martin Buck, Setsuko K. Chambers, Prafull Ghatage, Charles H. Pippitt, John V. Brown, Allan Covens, Raj Nagarkar, Margaret Davy, Charles A. Leath, Hoa P. Nguyen, Daniel E. Stepan, David M. Weinreich, Marjan Tassoudji, Yu-Nien Sun, Ignace Vergote
Издательство: Lippincott Williams & Wilkins
Источник: Journal of Clinical Oncology
Ключевые слова: Ovarian cancer diagnosis and treatment, Angiogenesis and VEGF in Cancer, Hormonal Regulation and Hypertension
Другие ссылки: Journal of Clinical Oncology (PDF)
Journal of Clinical Oncology (HTML)
PubMed (HTML)
Journal of Clinical Oncology (HTML)
PubMed (HTML)
Открытый доступ: bronze
Том: 30
Выпуск: 4
Страницы: 362–371