A Phase II Trial of Bortezomib and Prednisone for Castration Resistant Metastatic Prostate Cancer
Received 5 April 2007 published online 15 October 2007.
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.
Departments of Medicine (Genitourinary Oncology Service), Radiology and Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center and Department of Medicine, Weill Medical College of Cornell University, New York, New York
Correspondence: Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 444, New York, New York 10021 (telephone: 646-422-4469; FAX: 212-988-0701).
Study received Memorial Sloan-Kettering Cancer Center institutional review board approval.
Supported by Millennium Pharmaceuticals, National Cancer Institute Grants CA102544 and CA05826, Prostate Cancer Foundation, the Sacerdote Fund and the PepsiCo Foundation for Prostate Cancer.
† Financial interest and/or other relationship with Millennium Pharmaceuticals.
ABSTRACT