Phase II study of KOS-862 in patients with metastatic androgen independent prostate cancer previously treated with docetaxel
Document Type
Article
Department
Haematology and Oncology, East Africa
Abstract
Based on the pre-clinical spectrum of activity in taxane-resistant cell lines, we evaluated KOS-862 (epothilone D; 12,13-desoxyepothilone B) as second-line chemotherapy in androgen-independent prostate cancer. Thirty-eight men with metastatic androgen-independent prostate cancer and evidence of progression following docetaxel-based chemotherapy were treated with KOS-862, 100 mg/m2 (maximum of 240 mg) i.v. weekly for 3 weeks, repeated every 4 weeks. The primary objective for this study was to determine the antitumor activity, measured by PSA decline by more then 50% confirmed 4 weeks later. Two patients (5.3%, 90% CI 1–16%) met criteria for confirmed PSA decline. While both of these patients had previously been treated with docetaxel, neither had confirmed docetaxel-refractory disease. None of the 24 patients with measurable disease had a confirmed partial response. Seventy-three percent of patients had an adverse event leading to dose delay, reduction, or treatment discontinuation. Neurological toxicity and fatigue predominated. Seventeen patients (44.7%) had treatment related grade 3 neurological adverse events including peripheral sensory neuropathy (n = 4, 10.5%), ataxia (n = 3, 7.9%), peripheral motor neuropathy (n = 1, 2.6%), involuntary muscle contractions (n = 1, 2.6%) and neuropathic pain (n = 1, 2.6%). One subject (2.6%) had a grade 4 treatment peripheral motor neuropathy. Further study of this dose and schedule of KOS-862 in this patient population cannot be recommended due to both lack of activity and excessive toxicity.
Publication (Name of Journal)
Investigational new drugs
DOI
DOI 10.1007/s10637-007-9068-1
Recommended Citation
Beer, T.,
Higano, C.,
Saleh, M.,
Dreicer, R.,
Hudes, G.,
Picus, J.,
Rarick, M.,
Fehrenbacher, L.,
Hannah, A.
(2007). Phase II study of KOS-862 in patients with metastatic androgen independent prostate cancer previously treated with docetaxel. Investigational new drugs, 25, 1-6.
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/30
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Comments
This work was published before the author joined Aga Khan University.