Phase II study of KOS-862 in patients with metastatic androgen independent prostate cancer previously treated with docetaxel

Tomasz (Tom) Beer, Celestia S. Higano, Mansoor Saleh, Robert Dreicer, Gary Hudes, Joel Picus, Mark Rarick, Louis Fehrenbacher, Alison L. Hannah

    Research output: Contribution to journalArticle

    45 Citations (Scopus)

    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.

    Original languageEnglish (US)
    Pages (from-to)565-570
    Number of pages6
    JournalInvestigational New Drugs
    Volume25
    Issue number6
    DOIs
    StatePublished - Dec 2007

    Fingerprint

    docetaxel
    Androgens
    Prostatic Neoplasms
    Peripheral Nervous System Diseases
    Drug Therapy
    Neuralgia
    Ataxia
    Muscle Contraction
    Fatigue
    Smooth Muscle
    desoxyepothilone B
    Appointments and Schedules
    Therapeutics

    Keywords

    • Docetaxel
    • Prostate cancer

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)
    • Oncology
    • Molecular Medicine

    Cite this

    Phase II study of KOS-862 in patients with metastatic androgen independent prostate cancer previously treated with docetaxel. / Beer, Tomasz (Tom); Higano, Celestia S.; Saleh, Mansoor; Dreicer, Robert; Hudes, Gary; Picus, Joel; Rarick, Mark; Fehrenbacher, Louis; Hannah, Alison L.

    In: Investigational New Drugs, Vol. 25, No. 6, 12.2007, p. 565-570.

    Research output: Contribution to journalArticle

    Beer, TT, Higano, CS, Saleh, M, Dreicer, R, Hudes, G, Picus, J, Rarick, M, Fehrenbacher, L & Hannah, AL 2007, 'Phase II study of KOS-862 in patients with metastatic androgen independent prostate cancer previously treated with docetaxel', Investigational New Drugs, vol. 25, no. 6, pp. 565-570. https://doi.org/10.1007/s10637-007-9068-1
    Beer, Tomasz (Tom) ; Higano, Celestia S. ; Saleh, Mansoor ; Dreicer, Robert ; Hudes, Gary ; Picus, Joel ; Rarick, Mark ; Fehrenbacher, Louis ; Hannah, Alison L. / Phase II study of KOS-862 in patients with metastatic androgen independent prostate cancer previously treated with docetaxel. In: Investigational New Drugs. 2007 ; Vol. 25, No. 6. pp. 565-570.
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    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.",
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    AU - Beer, Tomasz (Tom)

    AU - Higano, Celestia S.

    AU - Saleh, Mansoor

    AU - Dreicer, Robert

    AU - Hudes, Gary

    AU - Picus, Joel

    AU - Rarick, Mark

    AU - Fehrenbacher, Louis

    AU - Hannah, Alison L.

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    N2 - 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.

    AB - 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.

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