Pilot study of epothilone B analog (BMS-247550) and estramustine phosphate in patients with progressive metastatic prostate cancer following castration Journal Article
| Authors: | Smaletz, O.; Galsky, M.; Scher, H. I.; Delacruz, A.; Slovin, S. F.; Morris, M. J.; Solit, D. B.; Davar, U.; Schwartz, L.; Kelly, W. K. |
| Article Title: | Pilot study of epothilone B analog (BMS-247550) and estramustine phosphate in patients with progressive metastatic prostate cancer following castration |
| Abstract: | Background: Several trials have demonstrated that the response proportions to microtubule agents in patients with prostate cancer are increased by the addition of estramustine phosphate (EMP). The epothilone B analog BMS-247550 is a novel microtubule agent that has shown activity in taxane-resistant tumors. We conducted a dose-escalation study to determine a safe dose of BMS-247550 to combine with EMP in patients with metastatic prostate cancer. Patients and methods: Chemotherapy-naive patients with castrate-metastatic prostate cancer were treated with intravenous BMS-247550 and oral EMP (280 mg three times daily for 5 days) every 3 weeks. Results: Thirteen patients were treated at two dose levels (35 and 40 mg/m2). Three of six patients treated at 40 mg/m2 developed grade 4 neutropenia, establishing 35 mg/m2 as the maximum-tolerated dose. Significant peripheral neuropathy (grade≥2) was related to dose level and infusion rate. A decline in prostate-specific antigen (PSA) of ≥50% was seen in 11 of 12 evaluable patients (92%) (95% confidence interval 76% to 100%). There were objective responses in soft tissue (57%) and bone metastasis (40%). Conclusions: The phase II dose of BMS-247550 combined with EMP is 35 mg/m2 over 3 h every 3 weeks. This combination is safe and ≥50% post-therapy declines in PSA were seen in 11 of 12 patients (92% ). |
| Keywords: | adult; clinical article; controlled study; treatment outcome; aged; bone neoplasms; middle aged; unclassified drug; clinical trial; fatigue; neutropenia; diarrhea; dose response; drug safety; antineoplastic agents; bone metastasis; paclitaxel; anorexia; adenocarcinoma; prostate specific antigen; carboplatin; edema; metastasis; controlled clinical trial; phase 2 clinical trial; sensory neuropathy; anemia; nausea; thrombocytopenia; vomiting; peripheral neuropathy; antineoplastic activity; dose-response relationship, drug; vinblastine; docetaxel; dyspnea; febrile neutropenia; prostate cancer; rash; confidence interval; prostate-specific antigen; prostatic neoplasms; pilot study; thrombosis; drug response; maximum tolerated dose; castration; antineoplastic agents, hormonal; taxane derivative; concentration (parameters); microtubules; allergic reaction; ixabepilone; epothilones; epothilone b; epothilone; anticoagulant agent; soft tissue metastasis; estramustine; estramustine phosphate; humans; human; male; priority journal; article |
| Journal Title: | Annals of Oncology |
| Volume: | 14 |
| Issue: | 10 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2003-04-01 |
| Start Page: | 1518 |
| End Page: | 1524 |
| Language: | English |
| DOI: | 10.1093/annonc/mdg415 |
| PUBMED: | 14504052 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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