Zyflamend
- (This
trial is currently CLOSED)
Purpose
and Objective: Subjects diagnosed with prostatic intraepithelial
neoplasia (PIN) at prostate biopsy are at increased risk of developing
prostate cancer on later biopsies. Currently there is no consensus as
to the optimal therapy for the chemoprevention of prostate cancer in
these subjects. We initiated a phase I clinical trial to asses the safety
and efficacy of the novel herbal anti-inflammatory, Zyflamend, to prevent
prostate cancer in high-risk subjects with PIN.
Methods:
Men ages 40-75 diagnosed with high-grade PIN (without prostate cancer)
on biopsy within the last six months were enrolled. No restrictions
were placed on PSA level. Patients could not be enrolled in other chemo
or herbal prevention trials. They were assigned to one of eight treatment
groups, with successive dose-escalation occurring in each group. Patients
were evaluated every three months for 18 months; at which time they
had a physical exam and blood samples drawn to monitor for toxicity,
check for fluctuations in PSA and testosterone, and monitor a battery
of inflammatory serum markers (CRP, Fibrinogen, IGFBP3, Apolipoprotein
A-1 and B). At 6, 12 and 18 months, 12-core transrectal ultrasound guided
biopsy of the prostate with a standard pathology kit was performed.
If a rapidly rising PSA (>50% of the previous value) was encountered
between scheduled six month periods, biopsy was indicated sooner. Biopsy
tissue was evaluated for the presence of PIN and/or prostate cancer
then stained for inflammatory biomarkers. A NCI common terminology criteria
for adverse events (v3.0) based questionnaire was used to monitor side
effects. Endpoints are completion of the 18 month protocol without adenocarcinoma
or diagnosis of adenocarcinoma prior to 18 months.
Results:
To date 23 patients have been enrolled, 4 have withdrawn; the expected
closure date is February 1, 2006. The median patient age is 65.1 years
with a median PSA level of 6.8. There have been no adverse events reported
or toxicities apparent. Five patients (22%) have complained of grade
I dyspepsia resolving spontaneously without intervention. Preliminary
results include a total of 17 biopsies performed in 11 patients. 14
of the 17 biopsies were performed per protocol at scheduled visits,
the remaining three were performed between scheduled visits. Of 17 biopsies
completed one returned positive for PIN (5.9%) and two have returned
with adenocarcinoma (11.8%).
Conclusions:
The novel herbal anti-inflammatory, Zyflamend, appears to be associated
with minimal toxicity and no serious adverse events when administered
orally. Short term biopsy results indicate a low progression rate, although
long-term efficacy awaits further studies.
