Phase II study of MLN8237 (alisertib), an investigational Aurora A kinase inhibitor, in patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal carcinoma
| Autor: | Salvatore A. Del Prete, Michael S. Gordon, Sudarshan Sharma, Hua Liu, Ursula A. Matulonis, Xiaofei Zhou, Sharad A. Ghamande, Russell J. Schilder, Hadi Danaee, Howard Fingert, Isabelle Ray-Coquard, Elzbieta Kutarska |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
medicine.medical_specialty Phases of clinical research Neutropenia Protein Serine-Threonine Kinases Gastroenterology Disease-Free Survival chemistry.chemical_compound Primary peritoneal carcinoma Aurora Kinases Internal medicine Medicine Fallopian Tube Neoplasms Humans Protein Kinase Inhibitors Peritoneal Neoplasms Aged Gynecology Aged 80 and over Ovarian Neoplasms business.industry Obstetrics and Gynecology Azepines Middle Aged medicine.disease medicine.anatomical_structure Pyrimidines Oncology chemistry Response Evaluation Criteria in Solid Tumors Alisertib Female business Ovarian cancer Febrile neutropenia Fallopian tube |
| Zdroj: | Gynecologic oncology. 127(1) |
| ISSN: | 1095-6859 |
| Popis: | Objectives Aurora A kinase (AAK), a key mitotic regulator, is implicated in the pathogenesis of several tumors, including ovarian cancer. This single-arm phase II study assessed single-agent efficacy and safety of the investigational AAK inhibitor MLN8237 (alisertib), in patients with platinum-refractory or ‐resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Methods Adult women with malignant, platinum-treated disease received MLN8237 50mg orally twice daily for 7days plus 14days' rest (21-day cycles). The primary endpoint was combined objective tumor response rate per Response Evaluation Criteria in Solid Tumors (RECIST) and/or CA-125 criteria. Secondary endpoints included response duration, clinical benefit rate, progression-free survival (PFS), time-to-progression (TTP), and safety. Results Thirty-one patients with epithelial ovarian (n=25), primary peritoneal (n=5), and fallopian tube carcinomas (n=1) were enrolled. Responses of 6.9–11.1month duration were observed in 3 (10%) patients with platinum-resistant ovarian cancer. Sixteen (52%) patients achieved stable disease with a mean duration of response of 2.86months and which was durable for ≥3months in 6 (19%). Median PFS and TTP were 1.9months. Most common drug-related grade ≥3 adverse events were neutropenia (42%), leukopenia (23%), stomatitis, and thrombocytopenia (each 19%); 6% reported febrile neutropenia. Conclusions These data suggest that MLN8237 has modest single-agent antitumor activity and may produce responses and durable disease control in some patients with platinum-resistant ovarian cancer. MLN8237 is currently undergoing evaluation in a phase I/II trial with paclitaxel in recurrent ovarian cancer. |
| Databáze: | OpenAIRE |
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