PD32-04 PHASE I/II CLINICAL TRIAL TO ASSESS SAFETY AND EFFICACY OF INTRATUMORAL AND SUBCUTANEOUS INJECTION OF HVJ-E TO CASTRATION RESISTANT PROSTATE CANCER PATIENTS

Abstract

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) III1 Apr 2016PD32-04 PHASE I/II CLINICAL TRIAL TO ASSESS SAFETY AND EFFICACY OF INTRATUMORAL AND SUBCUTANEOUS INJECTION OF HVJ-E TO CASTRATION RESISTANT PROSTATE CANCER PATIENTS Kazutoshi Fujita, Yasutomo Nakai, Koji Hatano, Norihiko Kawamura, Atsunari Kawashima, Takeshi Ujike, Akira Nagahara, Motohide Uemura, Yasufumi Kaneda, and Norio Nonomura Kazutoshi FujitaKazutoshi Fujita More articles by this author , Yasutomo NakaiYasutomo Nakai More articles by this author , Koji HatanoKoji Hatano More articles by this author , Norihiko KawamuraNorihiko Kawamura More articles by this author , Atsunari KawashimaAtsunari Kawashima More articles by this author , Takeshi UjikeTakeshi Ujike More articles by this author , Akira NagaharaAkira Nagahara More articles by this author , Motohide UemuraMotohide Uemura More articles by this author , Yasufumi KanedaYasufumi Kaneda More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.680AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope; HVJ-E) has a novel antitumor effect: HVJ-E fused to prostate cancer cells via cell surface receptor, causing apoptosis of prostate cancer cells in vitro and in vivo. HVJ-E also induces anti-tumor immunity by activating natural killer (NK) cells and cytotoxic T cells as well as suppressing regulatory T cells in vivo. We conducted an open-label, single-arm Phase I/II clinical trial in castration resistant prostate cancer (CRPC) patients to determine the safety and efficacy of intratumoral and subcutaneous injection of HVJ-E. METHODS Patients with CRPC who were docetaxel-resistant or could not receive docetaxel treatment were eligible. HVJ-E was administered directly to prostate on day 1 and subcutaneously on day 5, 8 and 12 in 28-day treatment cycles using a 3 + 3 dose-escalation design. Treatment was repeated for 2 cycles. The primary endpoint was to evaluate safety and tolerability. The secondary endpoint was to analyze tumor immunity and anti-tumor effect. RESULTS Seven patients were enrolled and a total of 6 patients received HVJ-E. Grade 2 or 3 adverse events (CTCAE Ver. 4.0) were urinary retention and lymphopenia, which were spontaneously recovered. No grade 4 adverse events were observed. Radiographically, 3 patients had a stable disease in low-dose group, and 1 patient had a stable disease and 2 had a progressive disease in high-dose group. PSA declines were observed in one patient of low-dose group from 14ng/ml to 1.9ng/ml after 2 cycles of HVJ-E treatment, and PSA response rate was 16.6%. Activity of NK cells was elevated from day 12 to day 28 after HVJ-E administration, while serum IL-6, IFN-alfa, IFN-beta and IFN-gamma levels were not affected by HVJ-E treatment. CONCLUSIONS Intratumoral and subcutaneous injections of HVJ-E are feasible and partially effective in CRPC patients. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e762 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Kazutoshi Fujita More articles by this author Yasutomo Nakai More articles by this author Koji Hatano More articles by this author Norihiko Kawamura More articles by this author Atsunari Kawashima More articles by this author Takeshi Ujike More articles by this author Akira Nagahara More articles by this author Motohide Uemura More articles by this author Yasufumi Kaneda More articles by this author Norio Nonomura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...