New drug delivery approach for the treatment of prostate cancer (preclinical results and phase I study results).
4661 Introduction: Treatment for localized prostate cancer includes observation, radiation and surgical therapy with or without androgen deprivation.. One potential relevant form of therapy is thermal therapy plus thermally sensitive liposomal encapsulated cytotoxic agents administered systemically, concentrated in the prostate, where the focused heat triggers drug release from the liposome.Extensive animal studies were performed in rodents and dogs to support the ongoing clinical study for the treatment of Prostate cancer . A study in dogs tested whether the BPH800 System, a transurethral microwave catheter heating system, would heat the prostate to temperatures high enough to activate the heat-sensitive liposomes. Detailed large and small animal toxicology studies were also performed. Preclinical Results: The drug is active against a range of xenografts, including PC3, a prostate tumor line, when the tumor region is heated to temperatures that lead to rapid drug release from the liposomes. Enhanced growth delay was observed, when compared with heat alone and drug alone. Dog studies demonstrated that the BPH800 System is capable of providing safe and reliable thermal therapy in that it consistently applied the heat needed to maintain the prostate at the liposomal drug-release temperature of 41°C-42°C for 60 minutes. The toxicology studies in large dogs established that the DLT was slightly lower than that of free drug. These data were used to design the starting dose for Phase I trials.The preclinical study results led to FDA clearance to conduct the first Phase I dose escalation trial to determine the MTD, PK, & safety of Thermadox™ when activated with thermal therapy for the treatment of prostate cancer. The study is currently in process and will be completed in early 2004. The poster will describe the framework of the Phase I study and its results.Assessment of the safety and efficacy of the treatment of prostate cancer is in progress; enrollment is continuing for the first Phase I study. [Table: see text].
Dhawan, M; Price, D; Trump, D; Kanter, P; Shore, N; Needham, D; Dewhirst, M
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