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LE Magazine September 2007

FDA Rejects Promising Prostate Cancer Drug

Reviewed and critiqued by Stephen B. Strum, MD, FACP (Life Extension Scientific Advisory Board Member) By William Faloon

How Provenge® Was Derailed

Provenge® was sabotaged by a minority of the FDA Advisory Panel who voted against it. The campaign to discredit Provenge® by those in the cancer establishment was “unprecedented,” according to Mark Thornton, MD, a former medical officer in the FDA Office of Oncology Products and volunteer president of the Sarcoma Foundation of America. Dr. Thornton authored an editorial titled “Black Day at the FDA” that opened by stating:

“Within an eight-hour period that day, the FDA succeeded in killing not one but two safe, promising therapies designed and developed to act by stimulating a patient’s immune system against cancer.” 30

—Wall Street Journal, May 14, 2007.

The other drug Dr. Thornton described is called Junovan™, which was shown to extend the lives of children afflicted with osteosarcoma.30,31 Despite clear survival advantages, the FDA denied approval of Junovan™ the same black day it denied Provenge®. (We discuss Junovan™ in detail in an article that appears later in this issue of Life Extension magazine.)

How Many Needless Deaths?

It is difficult to calculate exactly how many American men perished because the federal government would not allow them to risk trying Provenge®, even though they faced probable death from their advanced prostate cancer.

One way of measuring the number of human life years lost is to look at one of the Provenge® studies showing how many months of average life were added to Provenge® recipients compared with placebo. Based on this analysis, for each year Provenge® was delayed, 11,250 human life years have been lost. Since the delay has been almost five years, the total loss caused by this bureaucratic delay in approving this one drug amounts to a startling 56,000 years of human life.

Even more appalling, the efficacy of Provenge® was shown in men who had already failed all conventional therapies. These advanced stages of cancer are difficult to treat, because the cancer cells have already developed survival mechanisms that make them extremely difficult to eradicate. The fact that Provenge® demonstrated such impressive survival benefits in men with these advanced forms of prostate cancer hints that it could be even more effective if administered in earlier stages of the disease—perhaps at the first sign of metastasis or in those men with highly adverse risk factors associated with short survival times.

Life Extension versus Federal Government

For the past three decades, Life Extension has sought to expose an insidious drug approval process that causes human beings to die, even though effective therapies to treat their diseases already exist. We have revealed many medications that the FDA dragged its feet in approving, resulting in a severe magnitude of needless suffering and death.4

There are no federal prohibitions against Americans engaging in all kinds of risky behaviors that provide no benefit to society or opportunity of extending human life.

That the government pretends it has to protect citizens against drugs that it has not approved, yet has no restrictions against people engaging in dangerous activities, is somewhat hypocritical. What it all boils down to, however, is defining the term “risk.”

We at Life Extension have long contended that any person with a serious illness should have the individual right to choose any therapy that they think may work. Therapies not FDA-approved should have a large warning label stating “not approved by the FDA for safety or effectiveness.” This would let each individual determine what “risk” they are willing to assume in order to be given a chance to continue enjoying the very basic right to life.

The article in this issue titled “Lifesaving Cancer Drugs Not Approved by the FDA” reveals additional effective medications that are being denied to seriously ill Americans by our own government.

On page 13 we describe the specific action that each one of you should take to encourage Congress to change the law, so that no American with a serious disease is ever again denied a promising therapy.

For the benefit of yourself and your loved ones, please use the convenient system we have developed to contact your Congressional members about the critical need to amend the law, so that those with serious disease can take full advantage of the latest medical technologies.

For longer life,

William Faloon

Note: To review a chart of all the human clinical studies using Provenge®, refer to the next page.

Overview of Provenge® Clinical Studies and Results

Study Name

Patient Population

Nature of PC

Results

Additional Info

Side Effects and Toxicity

D9905 Phase II, open label study 22,33	19 patients; prior definitive RP or RT followed by PSAR with PSA levels 0.4-6.0 ng/mL	ADPC	72% (13 of 18) evaluable patients prolonged PSADT with 62% increase [4.9 to 7.9 months] (p = 0.09).	Of 13 with increased PSADT, 5 had PSADT > 12 months and 1 with PSADT increase from 3.5 to 66.6 months.	Most common side effects: fever and chills (low grade and short duration).
Provenge® + Avastin® (APC8015) 21	22 patients with PSAR after RP, RT, or both with rising PSA between 0.4 and 6.0 ng/mL; Provenge® given at weeks 0, 2, and 4; Avastin® 10mg/kg after vaccine and every 2 weeks until PC progression or toxicity.	ADPC	Median PSADT in 20 evaluable patients: pre-Rx 6.9 months vs. 12.7 months post-Rx, approaching a 90% increase in PSADT (p=0.01). 6 patients with increase at least 200% (range 214-758%).	Median time to progression was 11.2 months and no patients with objective PC progression. Drop in PSA from baseline in 9 patients ranging from 6-72%, with 3 patients with at least a 25% decline. One patient had 50% or more decrease from baseline (2.78 to 0.78). Lack of concurrent control arm in study.	4 patients removed from study due to toxicity (congestive heart failure, gastrointestinal hemorrhage, cerebrovascular ischemia, and proteinuria). These are side effects attributable to Avastin®.
Phase I/II Open Label Study 29	12 patients with advanced metastatic disease and heavy pretreatment including chemo and 19 patients with non-metastatic disease and PSAR post ADT. Both groups defined as AIPC.	AIPC	3 patients with > 50% decrease in PSA + 3 more patients with 25-49% decreases in PSA. No improvements in bone scans or soft tissue disease observed.	Median time to disease progression for phase I patients = 12 weeks, and median time to progression for phase II patients = 29 weeks. 7 of the 19 phase II patients had not progressed after 1-year follow-up period.	Median time to disease progression was 31.7 weeks for patients who received more than 100 x 106 cells/infusion compared with 12.1 weeks for patients who received fewer cells (p =.013). Fever in 15 patients (14.7%) within 2 hours of infusion. 2 febrile reactions scored grade 3 and 13 grade 1 or 2. Mild myalgias occurred 1 or 2 days after infusions in 2 patients; mild fatigue in 1 patient.
Phase I Open-Label Study 34	13 patients with metastatic PC	AIPC	3 of 12 evaluable patients with > 50% PSA. 2 of above with also in PAP.	Median time to disease progression was 135 days after registration (range, 30–274 days).	5 patients with mild (grade 1–2) short-lived fever and/or chills. 5 patients with myalgia, pain, and fatigue. One patient developed grade 3 fatigue.
D9901 (APC8015) Phase III, randomized study of Provenge® (with comparison cross-over study); presented at ASCO 2005 Orlando meeting and pub-lished in JCO5,9,32,35	127 patients at 19 study sites: 82 received Provenge®, 45 received placebo; infusions given weeks 0, 2, and 4; comparison crossover to APC8015F (34 patients) after progression on placebo arm.	AIPC; with progression after ADT; no symptoms.	Time to objective progression (TTP) NOT significantly different, but with trend for active Rx arm (p = 0.052). TTP 11.7 weeks for Provenge® vs. 10.0 weeks for placebo. PSA not used to determine TTP.	Overall survival 25.9 months with Provenge® vs. 21.4 months with placebo; p=0.01, hazard ratio 1.7 and 95% confidence interval 1.13-2.56. At 3 years, 34% survival in Provenge® arm vs. 11% in placebo arm (p = 0.005). In subset of patients with immune monitoring, there was an 8-fold advantage in T-cell stimulation for Provenge® vs. placebo.	Toxicity: rigors (59.8% vs. 8.9%), pyrexia (29.3% vs. 2.2%), tremor (9.8% vs. 0%), and feeling cold (8.5% vs. 0%) for Provenge® vs. placebo.
Update of D9901 presented at Prostate Cancer Foundation Oct 19-21, 2006 36	See above	As above		Median PC specific survival 35.2 months with Provenge® vs. 23.5 months with placebo; Hazard ratio 2.04 for PC specific survival in favor of Provenge® and 1.71 for risk of overall survival in favor of Provenge®.
Provenge® followed by Taxotere,® presented at Chemotherapy Foundation Symposium in NYC 36	147 patients randomized to Provenge® vs. placebo with cross-over in 56 progressing patients	AIPC	Median survival 34.5 months Provenge® Taxotere® vs. 20.2 months for placebo Taxotere®	Cross-over patients: median survival 25.7 months for placebo APC8015F Taxotere®
D9902A 37	65 pts randomized to Provenge® versus 33 placebo	AIPC; with progression after ADT; no symptoms.	Primary endpoint TTP, and secondary endpoint overall survival	No difference between Provenge® vs. placebo, but multivariate analysis of 5 prognostic items showed Provenge® to be significant (p = 0.023). Integrated analysis of D9901 & D9902A (identical variables in both studies) showed median survival with Provenge® of 23.2 months vs. 18.8 months for placebo (p = 0.011; HR 1.5).

Glossary of Terms

ADPC: Androgen dependent prostate cancer
ADT: Androgen deprivation therapy
AIPC:Androgen independent prostate cancer
HR: Hormone refractory
PAP: Prostatic acid phosphatase
PC: Prostate cancer
Post-Rx: After treatment
Pre-Rx: Before treatment
PSA: Prostate-specific antigen
PSADT: Prostate-specific antigen doubling time
PSAR: Prostate-specific antigen only recurrence
RP: Radical prostatectomy
RT: Radiotherapy
TTP: Time to progression

What You Can Do to Stop Needless Cancer Deaths

References

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