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710 DOSE FINDING AND EFFICACY PHASE 2 STUDY OF INECALCITOL, A NEW VDR AGONIST, IN COMBINATION WITH DOCETAXEL-PREDNISONE REGIMEN FOR CASTRATION-RESISTANT PROSTATE CANCER (CRPC) PATIENTS (PTS)

2011; Lippincott Williams & Wilkins; Volume: 185; Issue: 4S Linguagem: Inglês

10.1016/j.juro.2011.02.1678

1527-3792

Jacques Médioni, G. Deplanque, Tristan Maurina, Jean-­Marc Ferrero, Jean-Michel Rodier, Éric Raymond, J. Ayllón, Stephanie Renaux, J. Dufour-Lamartinie, Stéphane Oudard,

Hormonal and reproductive studies

You have accessJournal of UrologyProstate Cancer: Advanced1 Apr 2011710 DOSE FINDING AND EFFICACY PHASE 2 STUDY OF INECALCITOL, A NEW VDR AGONIST, IN COMBINATION WITH DOCETAXEL-PREDNISONE REGIMEN FOR CASTRATION-RESISTANT PROSTATE CANCER (CRPC) PATIENTS (PTS) Jacques Medioni, Gael Deplanque, Tristan Maurina, Jean-Marc Ferrero, Jean-Michel Rodier, Eric Raymond, Jorge Ayllon, Stephanie Renaux, Jean-Francois Dufour-Lamartinie, and Stephane Oudard Jacques MedioniJacques Medioni Paris, France , Gael DeplanqueGael Deplanque Paris, France , Tristan MaurinaTristan Maurina Besançon, France , Jean-Marc FerreroJean-Marc Ferrero Nice, France , Jean-Michel RodierJean-Michel Rodier Paris, France , Eric RaymondEric Raymond Clichy, France , Jorge AyllonJorge Ayllon Paris, France , Stephanie RenauxStephanie Renaux Paris, France , Jean-Francois Dufour-LamartinieJean-Francois Dufour-Lamartinie Paris, France , and Stephane OudardStephane Oudard Paris, France View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1678AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Inecalcitol is a novel Vitamin D Receptor (VDR) agonist which shows high antiproliferative effects in human cancer cell lines and a 100-fold lower hypercalcemic activity than calcitriol the natural ligand of VDR. METHODS Escalating dosages of inecalcitol were combined to chemotherapy in naive metastatic CRPC patients. Safety and efficacy were evaluated in groups of 3–6 patients receiving inecalcitol every other day, daily or twice a day on a 21-day cycle in combination with docetaxel (75mg/m2 q3w) and oral prednisone (5mg bid). Patients received up to six cycles unless unacceptable toxicity or disease progression. Primary endpoint was dose limiting toxicity (DLT) defined as G3 hypercalcemia within the first cycle. Efficacy endpoint was PSA response defined as ≥30% decline within 3 months. RESULTS Eight dose levels from 40 to 8000 μg have been evaluated in 54 pts; 83% had bone metastases, 13% had visceral disease only. Median age was 71 years [range, 49–87], median Gleason score (Gs) 7 and median PSA 28.5 ng/mL [range, 0.8–962.4]. DLT occurred in 2/4 patients receiving 8000 μg/day after 1 and 2 weeks of treatment. Calcemia normalized in few days after interruption of treatment. The 2 other experienced only G2 and were stepped down to 4000 μg. After dose reduction, calcemia remained within normal ranges and G1.The Maximum Tolerated Dose is defined at 4000 μg qd. Most of adverse events reported were grade 2. G3–4 were mainly hematological toxicity. Frequency of AEs related to docetaxel did not seem to be modified. 82% of the patients had ≥30% PSA decline within 3 months of treatment whereas in historical data around 65% are responder with docetaxel as a single agent. PSA response was observed after 1 cycle of treatment in 43% of the patients. Time to biochemical relapse defined as an increase of 25% over nadir was 169 days. CONCLUSIONS High antiproliferative daily dose of inecalcitol, a new VDR, agonist has been safely used in combination with docetaxel in CRPC patients. This combination treatment shows encouraging PSA response (> 30% PSA response: 82%). A multicenter randomized double blind Phase 3 study is forecasted to confirm these results. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e285-e286 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Metrics Author Information Jacques Medioni Paris, France More articles by this author Gael Deplanque Paris, France More articles by this author Tristan Maurina Besançon, France More articles by this author Jean-Marc Ferrero Nice, France More articles by this author Jean-Michel Rodier Paris, France More articles by this author Eric Raymond Clichy, France More articles by this author Jorge Ayllon Paris, France More articles by this author Stephanie Renaux Paris, France More articles by this author Jean-Francois Dufour-Lamartinie Paris, France More articles by this author Stephane Oudard Paris, France More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...