Liproca Depot: A New Antiandrogen Treatment for Active Surveillance Patients

Abstract

Background: There is increasing interest in nonmorbid treatments for low-and intermediate-risk prostate cancer with fewer side effects than surgery or radiotherapy. Objective: To investigate the tolerability, safety, and antitumor effects of the intraprostatic NanoZolid depot formulation Liproca Depot (LIDDS AB, Uppsala, Sweden) with antiandrogen 2-hydroxyflutamide (2-HOF) in men with low-or intermediate-risk localized prostate cancer managed with active surveillance. Design, setting, and participants: This clinical phase 2b trial, LPC-004, involved 61 patients. The 2-HOF-containing formulation Liproca Depot was injected transrectally into the prostate under ultrasound guidance. A single dose of 35% or 45% of the prostate volume (study part 1) and a fixed dose of 16 or 20 ml (study part 2) of the formulation were evaluated. Outcome measurements and statistical analyses: The primary endpoints were tolerability and the reduction in serum prostate-specific antigen (PSA) 5 mo after injection. Antitumor effects were evaluated with magnetic resonance imaging (MRI) and prostate biopsies. Quality of life was assessed using a validated questionnaire (International Prostate Symptom Score). Results and limitations: All doses were safe and well tolerated, without hormonal side effects. In part 2 of the study, the PSA reduction was greatest for the group receiving 16 ml, with an average decrease of 14%, and 95% of patients had a PSA reduction. Some 78% of patients showed a prostate volume decrease compared to baseline. Prostate MRI and biopsies confirmed stable or reduced lesion size. However, post treatment biopsies were performed at the discretion of the investigator, and not routinely. Most patients were amenable to a second injection. Conclusions: PSA and prostate volume decreased in most patients. Indications of efficacy were shown by post-treatment MRI and biopsies demonstrating stabilization or regression in the majority of cases.

A feasibility study of the therapeutic response and durability of short-term androgen targeted therapy in early prostate cancer managed by surveillance: The Therapeutics in Active Prostate Surveillance (TAPS01) study

“…Schweizer et al [21] reported on shortterm ATT with apalutamide in 22 men on AS in the USA using systematic biopsy outcomes as the primary endpoint. The concept of direct intraprostatic antiandrogens has also been recently published by the well-respected AS group from Toronto [31]. In that study the primary measure was a reduction in PSA, but MRI, mainly used to look at the effect on gland volumes, did reveal a reduction in Prostate Imaging-Reporting and Data System score in nine out of61 men.…”

Tissue distribution of ethanol after intraprostatic injection using a porous needle

“…If a precise method for intraprostatic injection is developed, a cytotoxic or a PCa-specific therapeutic agent could be injected in a manner that would allow for tumor infiltration while avoiding injury to extraprostatic anatomical structures and prostatic urethra. Up until now, use of intraprostatic injection in the treatment of prostate disease has been limited to early phase clinical trials of antiandrogen or gene therapy (3,9). Intraprostatic injection of EtOH have been studied extensively for the therapy of benign prostatic hyperplasia (10)(11)(12).…”

“…The use of focal therapies is supported by high precision of multiparametric magnetic resonance imaging (mpMRI) in localizing clinically significant PCa ( 1 , 2 ). Furthermore, it has recently been proposed that such nonmorbid treatment modalities, with negligible effects on urinary, sexual and bowel function, will be beneficial as an alternative to PCa surveillance, halting disease progression, and delaying or eliminating the need for active therapy ( 3 , 4 ). Provided that targeted intraprostatic therapeutics become available over subsequent years, then intraprostatic injection may serve as an ideal delivery modality.…”

Round up

“…A multicenter phase 2b single-blind RCT evaluated the safety and efficacy of LD in men with low to intermediate-risk PCa (Gleason score of 3 + 3 or 3 + 4 and PSA ≤20 ng/ml) assigned to AS. [ 7 ]…”