Randomized phase II trial of docetaxel plus prednisone in combination with placebo or AT-101, an oral small molecule Bcl-2 family antagonist, as first-line therapy for metastatic castration-resistant prostate cancer
| Autor: | Guru Sonpavde, J. R. Caton, V. Matveev, Matthew D. Galsky, William R. Berry, Lance Leopold, M. Brookes, M.T. Fleming, John M. Burke, Thomas E. Hutson, J. T. Holmlund, Brian A. Wood, P. A. Karlov |
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| Rok vydání: | 2011 |
| Předmět: |
Oncology
Male medicine.medical_specialty Phases of clinical research Bone Neoplasms Docetaxel Kaplan-Meier Estimate Neutropenia Adenocarcinoma Placebo Gastroenterology law.invention Placebos Prostate cancer Randomized controlled trial law Prednisone Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Aged Aged 80 and over business.industry Hazard ratio Gossypol Prostatic Neoplasms Hematology Middle Aged medicine.disease Neoplastic Cells Circulating Treatment Outcome Proto-Oncogene Proteins c-bcl-2 Lymphatic Metastasis Taxoids business Orchiectomy medicine.drug |
| Zdroj: | Annals of oncology : official journal of the European Society for Medical Oncology. 23(7) |
| ISSN: | 1569-8041 |
| Popis: | Background AT-101 (A), a small molecule oral inhibitor of the Bcl-2 family, has activity alone and in combination with docetaxel (Taxotere) and prednisone (DP) in metastatic castration-resistant prostate cancer (mCRPC). A randomized, double-blind, placebo-controlled phase II trial compared DP combined with either AT-101 (A) or placebo in chemonaive mCRPC. Patients and methods Men with progressive mCRPC despite androgen deprivation were eligible and randomized 1 : 1. Patients received docetaxel (75 mg/m2 day 1) and prednisone 5 mg orally twice daily every 21 days with either AT-101 (40 mg) or placebo twice daily orally on days 1–3. The primary end point was overall survival (OS). Results Two hundred and twenty-one patients were randomly assigned. Median OS for AT-101 plus docetaxel–prednisone (ADP) and placebo–DP was 18.1 versus 17.8 months [hazard ratio (HR) 1.07, 95% confidence interval 0.72–1.55, P = 0.63]. Secondary end points were also not statistically different. Grade 3/4 toxic effects for ADP versus placebo–DP were cardiac events (5% versus 2%), lymphopenia (23% versus 16%), neutropenia (47% versus 40%), ileus (2% versus 0%) and pulmonary embolism (6% versus 2%). In a subgroup of high-risk mCRPC (n = 34), outcomes appeared to favor ADP (median OS 19 versus 14 months). Conclusions AT-101 was tolerable but did not extend OS when combined with DP in mCRPC; a potential benefit was observed in high-risk patients. |
| Databáze: | OpenAIRE |
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