Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401 Journal Article
| Authors: | Kelly, W. K.; Halabi, S.; Carducci, M.; George, D.; Mahoney, J. F.; Stadler, W. M.; Morris, M.; Kantoff, P.; Monk, J. P.; Kaplan, E.; Vogelzang, N. J.; Small, E. J. |
| Article Title: | Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401 |
| Abstract: | Purpose: A randomized, placebo-controlled study based on preclinical and clinical data that supports the potential role of vascular endothelial growth factor in prostate cancer was performed to evaluate the addition of bevacizumab to standard docetaxel and prednisone therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).Patients and Methods: Patients with chemotherapy-naive progressive mCRPC with Eastern Cooperative Oncology Group performance status ≤ 2 and adequate bone marrow, hepatic, and renal function were randomly assigned to receive docetaxel 75 mg/m2 intravenously (IV) over 1 hour for 21 days plus prednisone 5 mg orally twice per day (DP) with either bevacizumab 15 mg/kg IV every 3 weeks (DP + B) or placebo. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), 50% decline in prostate-specific antigen, objective response (OR), and toxicity.Results: In total, 1,050 patients were randomly assigned. The median OS for patients given DP + B was 22.6 months compared with 21.5 months for patients treated with DP (hazard ratio, 0.91; 95% CI, 0.78 to 1.05; stratified log-rank P = .181). The median PFS time was superior in the DP + B arm (9.9 v 7.5 months, stratified log-rank P < .001) as was the proportion of patients with OR (49.4% v 35.5%; P = .0013). Grade 3 or greater treatment-related toxicity was more common with DP +B (75.4% v 56.2%; P ≤ .001), as was the number of treatment-related deaths (4.0% v 1.2%; P = .005).Conclusion: Despite an improvement in PFS and OR, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC and was associated with greater toxicity. © 2012 by American Society of Clinical Oncology. |
| Keywords: | adult; cancer survival; controlled study; treatment outcome; aged; disease-free survival; middle aged; major clinical study; overall survival; prednisone; clinical trial; disease course; mortality; bevacizumab; placebo; cancer combination chemotherapy; drug safety; drug withdrawal; hypertension; liver function; side effect; unspecified side effect; united states; comparative study; disease free survival; antineoplastic agent; adenocarcinoma; prostate specific antigen; progression free survival; controlled clinical trial; infection; anemia; bone marrow; mucosa inflammation; nausea; randomized controlled trial; stomatitis; antineoplastic combined chemotherapy protocols; dehydration; odds ratio; risk factors; weight reduction; drug resistance; pathology; drug resistance, neoplasm; risk factor; time; time factors; risk assessment; risk; docetaxel; monoclonal antibody; dyspnea; febrile neutropenia; pneumonia; prostate-specific antigen; prostatic neoplasms; blood; neutrophil; kidney function; heart infarction; multicenter study; thrombosis; prostate tumor; androgen antagonists; colitis; chi-square distribution; taxoids; clostridium difficile infection; phase 3 clinical trial; antiandrogen; antineoplastic agents, hormonal; kaplan meier method; embolism; double blind procedure; double-blind method; brain ischemia; digestive system perforation; proteinuria; leukocyte; antineoplastic hormone agonists and antagonists; granulocyte; heart muscle ischemia; placebos; taxoid; chi square distribution; castration resistant prostate cancer; thrombus; kaplan-meier estimate; antibodies, monoclonal, humanized; calicivirus infection; left ventricular diastolic dysfunction; left ventricular systolic dysfunction |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 30 |
| Issue: | 13 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2012-05-01 |
| Start Page: | 1534 |
| End Page: | 1540 |
| Language: | English |
| DOI: | 10.1200/jco.2011.39.4767 |
| PROVIDER: | scopus |
| PMCID: | PMC3383121 |
| PUBMED: | 22454414 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 30 August 2012" - "CODEN: JCOND" - "Source: Scopus" |
