Activity of second-line chemotherapy in docetaxel-refractory hormone-refractory prostate cancer patients: Randomized phase 2 study of ixabepilone or mitoxantrone and prednisone Journal Article
| Authors: | Rosenberg, J. E.; Weinberg, V. K.; Kelly, W. K.; Michaelson, D.; Hussain, M. H.; Wilding, G.; Gross, M.; Hutcheon, D.; Small, E. J. |
| Article Title: | Activity of second-line chemotherapy in docetaxel-refractory hormone-refractory prostate cancer patients: Randomized phase 2 study of ixabepilone or mitoxantrone and prednisone |
| Abstract: | BACKGROUND. This randomized, noncomparative, multicenter, clinical trial evaluated ixabepilone or mitoxantrone/prednisone (MP) as second-line chemotherapy for taxane-refractory, hormone-refractory, prostate cancer (HRPC). METHODS. Patients with HRPC that progressed during or within 60 days of cessation of taxane chemotherapy were randomly selected with equal probability to ixabepilone 35 mg/m2 intravenously every 3 weeks, or mitoxantrone 14 mg/m2 intravenously every 3 weeks and prednisone 5 mg orally twice daily. Treatment continued until progression or toxicity; crossover was allowed. RESULTS. Forty-one patients were accrued to each arm of the study. The median number of cycles administered for each arm was 3. Median survival from protocol entry was 10.4 months with ixabepilone and 9.8 months with MP. Prostate-specific antigen (PSA) declines of ≥50% were observed in 17% of ixabepilone (95% CI, 7-32) and 20% of second-line MP patients (95% CI, 9-35). Partial responses were observed in 1 of 24 ixabepilone and in 2 of 21 MP patients with evaluable measurable disease. Median duration of second-line ixabepilone and MP treatment was 2.2 months and 2.3 months, respectively. For third-line crossover treatment, PSA declines of ≥50% were observed in 3 of 27 ixabepilone-treated and 4 of 15 MP-treated patients. Prior taxane response was associated with an increased likelihood of second-line ixabepilone or MP response. Low baseline lactate dehydrogenase and absence of visceral metastases independently predicted improved survival. The most common grade 3/4 toxicity associated with second-line treatment was neutropenia (54% of ixabepilone patients and 63% of MP patients). CONCLUSIONS. Ixabepilone and MP had modest activity as second-line chemotherapy for docetaxel-refractory HRPC. The median survival for the entire cohort treated in this study was 9.8 months. © 2007 American Cancer Society. |
| Keywords: | adult; cancer survival; controlled study; treatment outcome; aged; aged, 80 and over; middle aged; survival rate; major clinical study; prednisone; clinical trial; constipation; fatigue; neutropenia; salvage therapy; diarrhea; drug dose reduction; drug efficacy; hypophosphatemia; liver function; side effect; outcome assessment; anorexia; adenocarcinoma; controlled clinical trial; phase 2 clinical trial; sensory neuropathy; anemia; kidney disease; nausea; randomized controlled trial; stomatitis; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; dehydration; hypercalcemia; drug effect; drug resistance, neoplasm; docetaxel; dizziness; drug hypersensitivity; febrile neutropenia; hyperuricemia; injection site reaction; prostate cancer; syncope; confidence interval; prostate-specific antigen; prostatic neoplasms; drug fatality; hypokalemia; hypotension; prothrombin time; survival time; thorax pain; probability; multicenter study; thrombosis; drug response; mitoxantrone; muscle weakness; hypoglycemia; sepsis; liver disease; lactate dehydrogenase; taxoids; randomization; taxane derivative; heart arrhythmia; hormone; crossover procedure; brain ischemia; heart atrium arrhythmia; mood disorder; ixabepilone; epothilones; neoplasms, hormone-dependent; motor neuropathy; refractory; pharyngitis; cross-over studies; urinary tract obstruction; taxane; estramustine; second-line therapy |
| Journal Title: | Cancer |
| Volume: | 110 |
| Issue: | 3 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2007-08-01 |
| Start Page: | 556 |
| End Page: | 563 |
| Language: | English |
| DOI: | 10.1002/cncr.22811 |
| PUBMED: | 17577218 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 114" - "Export Date: 17 November 2011" - "CODEN: CANCA" - "Source: Scopus" |
