A phase I/II dose-escalation study of exisulind and docetaxel in patients with hormone-refractory prostate cancer

Christopher W. Ryan, Walter M. Stadler, Nicholas J. Vogelzang

    Research output: Contribution to journalArticle

    14 Scopus citations

    Abstract

    OBJECTIVE: To determine the safety and efficacy, in a dose-escalation study, of exisulind (an oral sulphone metabolite of sulindac thought to induce apoptosis in malignant cells by inhibiting cGMP-phosphodiesterase) combined with docetaxel in men with hormone-refractory prostate cancer (HRPC), as pre-clinical studies suggested activity against prostate cancer and synergy with cytotoxic agents. PATIENTS AND METHODS: Thirty-four patients with HRPC were treated with oral exisulind twice daily for 21-day cycles and intravenous docetaxel given for 1 h on the first day of each cycle. Three dose levels were assessed, combining exisulind 150 and 250 mg twice daily with docetaxel at 60 or 75 mg/m2. Toxicity was then evaluated using standard criteria. RESULTS: The recommended phase II dose was determined to be exisulind 250 mg and docetaxel 60 mg/m2, with escalation to 75 mg/m2 after cycle 1, as tolerated. The most common grade 3-4 toxicities among all patients were neutropenia (56%), infection (24°/o) and hyperglycaemia (18%). Twelve of 32 evaluable patients (38%, 95% confidence interval, Cl, 23-55%) had a decline in PSA by at least half. Only four of 17 evaluable patients (95% Cl, 1-47<%) treated at the phase II dose level had such a decline in PSA. The median (95% Cl) overall survival of all patients was 16 (12.9-19.7) months and median progression-free survival 4.7 (2.7-5.2) months. CONCLUSION: The combination of exisulind and docetaxel was tolerable in patients with HRPC. The PSA response rates do not suggest an improvement over historical data with single-agent docetaxel in this population.

    Original languageEnglish (US)
    Pages (from-to)963-968
    Number of pages6
    JournalBJU international
    Volume95
    Issue number7
    DOIs
    StatePublished - May 1 2005

    Keywords

    • Docetaxel
    • Exisulind
    • Hormone-refractory prostate cancer

    ASJC Scopus subject areas

    • Urology

    Fingerprint Dive into the research topics of 'A phase I/II dose-escalation study of exisulind and docetaxel in patients with hormone-refractory prostate cancer'. Together they form a unique fingerprint.

  • Cite this