"Advanced prostate cancer is difficult to treat - and the drug
therapies currently available to these patients have not been very
effective, especially in patients whose disease has progressed after
chemotherapy
treatment,"

Well, maybe they ought to try them on men EARLY in their recurrence!
The damn problem is that they don't test doodly-squat on hardly anyone
but hormone-refractory Pts. By that point the PCa is probably
widespread. I bet RP or RT would not be very effective either if you
waited until that point. :-/ Why not try this stuff on Pts for whom it
might make more than a 6 mo. difference? Like me.

BTW I haven't updated lately, and my news is not good. Although I
reached a milestone 5 years a week ago today, my last 3-mo. PSA went
from 1.1 to 1.6, a 45% increase. I think my honeymoon is nearing its
end. But my Vandy med-onc still says he wouldn't start ant Tx or get
any Dx tests.

Bill Denton
RP 2/12/02
PSA 1.6
Memphis

I get frustrated with news releases.
Not enough information and getting hopes up.
http://www.medscape.com/viewarticle/551689?rss
Pertuzumab Ineffective in Hormone-Refractory Prostate Cancer

Allison Gandey

February 5, 2007 — Results of a phase 2 trial evaluating pertuzumab, a
second-generation anti–human epidermal growth factor receptor (EGFR) 2
antibody, show that not a single patient achieved the primary end point of a
greater than 50% decline in prostate-specific antigen. "Pertuzumab has no
clinically significant single-agent activity in castrate patients with
hormone-refractory prostate cancer at either of the tested dose levels," the
researchers report in the January 20 issue of the Journal of Clinical
Oncology.

In this open-label phase 2 study, lead author Johann Sebastian de Bono, PhD,
from the Royal Marsden Hospital, in Surrey, United Kingdom, and colleagues
evaluated the efficacy and safety of 2 doses of pertuzumab. But in contrast
to previous results reported in ovarian cancer for the product, marketed
under the brand name Omnitarg by Roche and Genentech, the investigators
found it was ineffective in prostate cancer.

In an accompanying editorial, Drs. David Solit and Neal Rosen, from the
Memorial Sloan-Kettering Cancer Center, in New York, write, "The take-home
lesson is that there remains little evidence for a significant role for HER2
or epidermal growth factor receptor as the primary driver of prostate
cancers. Given the lack of efficacy seen with these agents, the use of HER
kinase inhibitors in multidrug combinations in prostate cancer patients
should be based on strong hypotheses and preclinical data." They add, "To
maximize the likelihood for success, the studies should be informed by
molecular profiling and mutational analyses of the tumor."

The editorialists point out that it has been common practice in oncology to
empirically test agents that show activity in 1 disease in all tumor types.
"On the basis of historical practices, it is therefore not surprising that
when therapies targeted to molecular lesions in specific tumors are
successful in 1 cancer type, these therapies are then tested in all cancers,
especially if they have only modest toxicity," they note.

Little Evidence for Significant Role of HER2 or EGFR in Prostate Cancers

In the current analysis, the investigators studied 68 castrate men with
hormone-refractory prostate cancer who had not received chemotherapy. A
total of 35 patients were treated with pertuzumab 420 mg administered
intravenously once every 3 weeks for 24 weeks.

Pertuzumab was well tolerated, but at interim analysis, the researchers
observed no prostate-specific antigen declines of greater than 50%, and
recruitment was stopped. A total of 33 patients were then treated at 1050 mg
and again, no prostate-specific antigen declines of greater than 50% were
observed.

In their editorial, Drs. Solit and Rosen ask, "Why have HER-kinase
inhibitors been so ineffective in prostate cancer?" They suggest that
insufficient target inhibition might have been achieved at the dose levels
studied. "Though the activity of pertuzumab, trastuzumab, and erlotinib in
ovarian, breast, and lung cancer suggests that target inhibition was likely
achieved with these agents in patients with prostate cancer, it is possible
that the level of target inhibition required to induce an antitumor response
may be different in these tumor types." They note that such a possibility
could be explained by differences in drug-to-target affinity in mutant vs
wild-type cells.

"Alternatively," they write, "the level of target inhibition required to
induce cell cycle arrest or apoptosis may differ in mutant cells, which are
oncogene addicted to the target compared with those that are not. Inadequate
target inhibition could have been excluded if pre- and posttreatment tumor
tissue had been collected for pharmacodynamic studies. Such studies were not
attempted, however, likely due to the difficulty of collecting such samples
in patients with prostate cancer."

The editorialists conclude that to accelerate the identification of
more-effective therapies for prostate cancer, efforts must be made to
develop novel minimally invasive technologies that will allow for genetic
stratification of patients in future clinical trials.

J Clin Oncol. 2007; 25:241-243, 257-262.

Looks like they reduced the dose in Cohort A
http://www.casodex.net/6096_25953_2_0_0.aspx
9 February 2007
Second generation anti-HER2 antibody fails in HRPC
Castrate chemotherapy-naïve patients with hormone-refractory prostate cancer
(HRPC) failed to respond to an antibody that is an established treatment for
breast cancer, UK researchers report.

The investigators administered a second generation anti-human epidermal
growth receptor 2 (anti-HER2) antibody, pertuzumab, to 68 patients in a
phase II trial.

Pertuzumab was administered to 35 patients (Cohort A) at 420 mg every 21
days, following an initial dose of 840 mg, and to the remaining 33 patients
(Cohort B) at 1050 mg every 21 days.

Co-author Johann Sebastian de Bono (Royal Marsden Hospital, Sutton) and team
report that, after three cycles of treatment, not a single patient had
achieved the primary end point of a 50% reduction in their prostate-specific
antigen level.

Pertuzumab halted disease progression in 12 patients in Cohort A, who had a
median progression-free survival (PFS) of 88 days, compared with 43 days for
Cohort A as a whole.

Pertuzumab halted disease progression in 10 patients in Cohort B, who had a
median PFS of 81 days, compared with 43 days for Cohort B as a whole.

The antibody was nevertheless well tolerated, de Bono et al report in the
Journal of Clinical Oncology.

"The most common adverse event assessed as related to pertuzumab was grade 1
or 2 diarrhea (37% in cohort A and 48% in cohort B; in addition, one patient
in cohort A suffered grade 3 diarrhea), followed by fatigue," they note.

In an accompanying editorial, David Solit and Neal Rosen (Memorial
Sloan-Kettering Cancer Center, New York, USA) commented that novel methods
for sampling and genotyping HRPCs must be developed if targeted agents such
as pertuzumab are to effectively treat the condition.

J Clin Oncol 2007; 25: 257–262

http://www.jco.org/cgi/content/abstract/25/3/257

This is the clinical trial http://www.clinicaltrials.gov/ct/show/NCT00058539
if anyone wants to view the criteria and exclusions and goals etc. It's
marked "Terminated"
J