A phase II trial of bortezomib and prednisone for castration resistant metastatic prostate cancer Journal Article
| Authors: | Morris, M. J.; Kelly, W. K.; Slovin, S.; Ryan, C.; Eicher, C.; Heller, G.; Scher, H. I. |
| Article Title: | A phase II trial of bortezomib and prednisone for castration resistant metastatic prostate cancer |
| Abstract: | Purpose: We defined the antitumor effects of bortezomib alone and in combination with prednisone in patients with progressive, castration resistant metastatic prostate cancer. Materials and Methods: A total of 30 men with progressive castration resistant disease were treated in 2 groups. Cohort 1 received 1.5 mg/m2 bortezomib intravenously twice weekly for 2 cycles (2 weeks on and 1 week off), followed by 1.6 mg/m2 weekly (4 weeks on and 2 weeks off). Prednisone (10 mg) was given orally throughout. Cohort 2 comprised patients with limited chemotherapy exposure who received a decreased dose of bortezomib (1.3 mg/m2) during the induction period with prednisone added only at disease progression. The primary end point was no evidence of disease progression at 12 weeks, defined as no increase in prostate specific antigen from baseline and no radiographic progression. Interleukin-6 was assessed to correlate with antitumor effects. Results: One of 24 evaluable patients (4%) achieved the primary end point. In cohort 1, 18 patients were treated, 13 were evaluable for response and 4 discontinued treatment due to toxicities, including 3 before attaining the point of being evaluable. No patient achieved the primary end point. In cohort 2, 12 patients were treated and 11 were evaluable for response. Toxicity was slightly mitigated compared with that in cohort 1. One patient achieved the primary end point. Interleukin-6 did not correlate with posttreatment prostate specific antigen changes in either cohort. Conclusions: Although interleukin-6 and other pathways regulated by nuclear factor-kappa B may be legitimate targets, treatment with bortezomib alone and with prednisone does not appear to have significant antitumor effects in patients with castration resistant metastatic prostate cancer. © 2007 American Urological Association. |
| Keywords: | adult; clinical article; treatment outcome; aged; aged, 80 and over; middle aged; survival rate; prednisone; clinical trial; constipation; fatigue; neutropenia; diarrhea; drug withdrawal; hypophosphatemia; monotherapy; side effect; follow-up studies; neoplasm staging; prostate specific antigen; metastasis; bortezomib; multiple cycle treatment; phase 2 clinical trial; sensory neuropathy; boronic acids; pyrazines; anemia; nausea; thrombocytopenia; antineoplastic combined chemotherapy protocols; drug administration schedule; hemoglobin; dose-response relationship, drug; risk assessment; dyspnea; fever; hyperglycemia; lymphocytopenia; syncope; prostate-specific antigen; prostatic neoplasms; alanine aminotransferase; aspartate aminotransferase; bilirubin; gastrointestinal toxicity; hyperkalemia; hypoalbuminemia; hypokalemia; hyponatremia; prostate; prostatectomy; neoplasm metastasis; interleukin 6; muscle weakness; urinary frequency; interleukin-6; cytokine production; neoplasm invasiveness; maximum tolerated dose; castration; orchiectomy; administration, oral; injections, intravenous; prostate carcinoma; sinus tachycardia; angina pectoris; corticosteroid therapy |
| Journal Title: | Journal of Urology |
| Volume: | 178 |
| Issue: | 6 |
| ISSN: | 0022-5347 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2007-12-01 |
| Start Page: | 2378 |
| End Page: | 2384 |
| Language: | English |
| DOI: | 10.1016/j.juro.2007.08.015 |
| PUBMED: | 17936848 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "CODEN: JOURA" - "Source: Scopus" |
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