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FDA rejects promising prostate cancer drug.

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Americans with life-threatening illnesses are denied access to promising therapies, but the federal government does nothing to prohibit high-risk activities that result in people being killed for no worthwhile purpose.

In early December 2006, the number one news topic related to three mountaineers who were lost while attempting to summit Mount Hood in Oregon despite dangerous weather conditions. Huge amounts of public resources were expended in an attempt to rescue the climbers, but to no avail: one was found dead, while the other two are still missing. (1)

During the very same week in December 2006, about 600 American men with advanced prostate cancer were on the verge of death. (2) The federal government prohibited a drug from reaching these prostate cancer victims, even though this drug had demonstrated efficacy in a carefully controlled clinical study. In fact, from the time of the release of the data on this drug in 2002, tens of thousands of American prostate cancer patients have died in the FDA's waiting room.

The government argues that advanced prostate cancer patients should not risk taking a drug that could cause side effects, even though all these patients face imminent death.

PARACHUTING TO DEATH OFF A BRIDGE

The third Saturday of October in Fayette County, West Virginia is called "Bridge Day." The highlight of the event involves hundreds of people parachuting off a high bridge. While a handful of minor injuries occur each year, last October's "Bridge Day" had one person die when his parachute did not open. This is the fourth fatality since this local tradition started. (3)

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There is no talk about banning the bridge jumps, but the federal government holds steadfast that promising drugs cannot be sold to terminally ill cancer patients until the FDA deems them as safe and effective.

No government restrictions on mountain climbing, bridge jumping, or other risky activities that contribute nothing to society, but an armada of federal officers, prosecutors, and FDA investigators are ready to pounce on anyone who dares offer a cancer therapy before it receives official approval.

DRUG SHOWN TO SAVE LIVES--BUT NOT APPROVED!

In mid-2004, I reported in this column about a randomized study involving men with late stage, metastatic prostate cancer who received either an immune-boosting vaccine called Provenge[R] or a placebo. (4) Patients were randomized to receive three vaccinations of Provenge[R] or placebo over a four-week period. Analysis of the data revealed that the single most important predictor of response to Provenge[R] was a patient's Gleason score, a measure of the aggressiveness of a patient's tumor. (5,6)

In patients with a Gleason score less than or equal to 7, the placebo group had an average time to cancer progression of 9.0 weeks, compared with 16.0 weeks for the Provenge[R] group. This finding was statistically significant with a p-value of 0.002 (indicating a two in 1000 probability of this occurring by chance alone). In addition, patients receiving Provenge[R] whose disease had not progressed six months after randomization had more than an eight-fold advantage in progression-free survival compared with those patients who received placebo (34.7% versus 4%).

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However, in the formal protocol of this government-approved study, the primary endpoint was the time to objective disease progression. Comparison of the Provenge[R]-treated group with the placebo group (using Kaplan-Meier survival curves) revealed a clinical benefit in the Provenge[R] treated patients (p-value=0.085) that approached but did not achieve the pre-specified primary endpoint of the study (p-value=0.05).

Provenge[R] was rejected by the FDA because the agency does not accept a retrospective subgroup analysis to show benefit of an experimental drug. To gain FDA approval, the company who created Provenge[R] planned a new study on men with Gleason scores of 7 or less. However, the company continued to follow patients in the original study, and the results continue to be impressive.

Of the 75 patients who entered the trial with a Gleason score of 7 or less, those receiving Provenge[R] were 3.7 times more likely to be alive after 30 months; this translates into 53% of the Provenge[R] group staying alive compared with only 14% of the placebo group. The Provenge[R] group also remained pain-free twice as long on average as the placebo group. (7)

A Wall Street Journal editorial commented on the FDA's deplorable delay by stating:

"We know that it works, and we know why it works. In any rational regulatory environment, that would be reason to speed Provenge[R] to market. But this is the FDA we are talking about." (8)

Fast forward to 2005, and the results of a new clinical study on Provenge[R] showed that three times as many advanced prostate cancer patients who received Provenge[R] were alive compared with patients receiving a placebo. (9-11) This study evaluated patients with prostate cancer who had progressive disease during androgen-deprivation therapy and who were categorized as having androgen-independent prostate cancer. This patient subset has a highly adverse prognosis, with most dying of the disease within a few years. In the Provenge[R] study, 34% of the patients receiving Provenge[R] were still alive after three years, compared with only 11% of men who were randomly assigned a placebo.

FDA CONDEMNS PLACEBO GROUP TO DEATH

Under FDA regulations, end stage prostate cancer patients had to risk receiving no therapy (the placebo) in the hope that they might be lucky enough to be in the study arm that received the promising drug (Provenge[R]). Life Extension has long advocated that cancer patients with advanced disease should not have to risk receiving a worthless placebo. Historical controls could be used instead of placebos to spare such patients almost certain death.

Prostate cancer kills more than 30,000 American men every year. (2) Provenge[R] has clearly demonstrated that it improves survival rates, yet the FDA still has not approved it. Considering that the FDA could have approved Provenge[R] as an experimental therapy as early as 2002, the agency's delay in approving this one drug alone may have resulted in the premature death of tens of thousands of men.

FDA ADVISORY PANEL RECOMMENDS APPROVAL OF PROVENGE[R]

On March 30, 2007, an FDA advisory panel reviewing all data on Provenge[R] recommended by a 13-4 vote that the agency approve it. (12-14) The approval of Provenge[R] would open a new front in the war on cancer, because its mode of action is different from that of existing chemotherapy drugs and radiation. Provenge[R] is a personalized therapy in which some of a patient's white blood cells are removed, programmed outside the body to attack prostate cancer cells, and then infused back into the body three or four days later.

FDA IGNORES ITS OWN ADVISORY PANEL

The clinical trials provided direct evidence that those who received Provenge[R] lived longer compared to control groups. (9,15-29) According to the FDA, however, these "survival advantages" had "issues." When these same "issues" were discussed in the Provenge[R] public meeting, the majority of the FDA Advisory Panel (in a 13-4 vote) thought that the issues, while relevant and important, were superseded by the solid immunology science behind the product.

Despite irrefutable data showing Provenge[R] extends life span, FDA bureaucrats succumbed to intense cancer establishment lobbying, and they denied approval. The FDA now insists on more data, which could take several years. This leaves those with advanced prostate cancer without a treatment that has the possibility of extending their lives.

HOW PROVENGE[R] WAS DERAILED

Provenge[R] was sabotaged by a minority of the FDA Advisory Panel who voted against it. The campaign to discredit Provenge[R] 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[TM], which was shown to extend the lives of children afflicted with osteosarcoma.30,31 Despite clear survival advantages, the FDA denied approval of Junovan[TM] the same black day it denied Provenge [R]. (We discuss Junovan[TM] 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[R], 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[R] studies showing how many months of average life were added to Provenge[R] recipients compared with placebo. Based on this analysis, for each year Provenge[R] 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[R] 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[R] 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[R], refer to the next page.

References

(1.) Available at: http://www.newwest.net/index.php/city/ article/hard_lessons_learned_from_oregon_deaths/C509/L509/. Accessed April 7, 2007.

(2.) Available at: www.prostatecancer foundation.org/site/ c.itIWK2OSG/b.97763/k.3BA8/PR_June_18_2004.htm. Accessed April 10, 2007.

(3.) Available at: www.fayettetribune.com/local/ local_story_296115637html?keyword=topstory. Accessed April 6, 2007.

(4.) Available at: http://www.lef.org/magazine/mag2004/ jun2004_awsi_01.htm. Accessed April 7, 2007.

(5.) Available at: http://findarticles.com/p/articles/ mi_m0EIN/is_2002_August_9/ai_90233563/pg_1. Accessed June 21, 2007.

(6.) Available at: http://investor.dendreon.com/ ReleaseDetail.cfm?ReleaseID=146750&Header=News. Accessed April 7, 2007.

(7.) Available at: http://www.asco.org/portal/site/ ASCO/enuitem.34d60f5624ba07fd506fe310ee37a01d/vgnextoid= 76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_ detail_view&confID=16&abstractID=731. Accessed April 7, 2007.

(8.) New cancer drugs. Wall Street Journal. January 26, 2004.

(9.) Small EJ, Schellhammer PF, Higano CS, et al. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006 Jul 1;24(19):3089-94.

(10.) Available at: www.investor.dendreon.com/ ReleaseDetail.cfm?ReleaseID=152362&Header=News. Accessed April 7, 2007.

(11.) Available at: www.prnewswire.com/cgi-bin/ stories.pl?ACCT=104&STORY=/www/story/10-31-2005/0004203756&EDATE=. Accessed May 21, 2007.

(12.) Available at: www.marketwatch.com/news/story/ dendreon-shares-skyrocket-fda-panels/story.px?guid= %7B615D317B-5A9E-4D78-91C0-E7D669AFF12B%7D. Accessed April 7, 2007.

(13.) Available at: http://today.reuters.com/news/ articleinvestingview=CN&WTmodLOC=C3-News-4&symbol=DNDN.O&storyID= 2007-03-30T172744Z_01_N30272779_RTRIDST_0_DENDREON-UPDATE-1- REPEAT.XML&type=qcna. Accessed April 7, 2007.

(14.) Available at: www.investor.dendreon.com/ReleaseDetail.cfm?ReleaseID=156146&Header=News. Accessed April 10, 2007.

(15.) Basler M, Groettrup M. Advances in prostate cancer immunotherapies. Drugs Aging. 2007;24(3):197-221.

(16.) Brand TC, Tolcher AW. Management of high risk metastatic prostate cancer: the case for novel therapies. J Urol. 2006 Dec;176(6 Pt 2):S76-S80.

(17.) So-Rosillo R, Small EJ. Sipuleucel-T (APC8015) for prostate cancer. Expert Rev Anticancer Ther. 2006 Sep;6(9):1163-7.

(18.) Lin AM, Hershberg RM, Small EJ. Immunotherapy for prostate cancer using prostatic acid phosphatase loaded antigen presenting cells. Urol Oncol. 2006 Sep;24(5):434-41.

(19.) Dawson NA. New molecular targets in advanced prostate cancer. Expert Rev Anticancer Ther. 2006 Jul;6(7):993-1002.

(20.) Anon. Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon. Drugs RD. 2006;7(3):197-201.

(21.) Rini BI, Weinberg V, Fong L, et al. Combination immunotherapy with prostatic acid phosphatase pulsed antigen-presenting cells (provenge) plus bevacizumab in patients with serologic progression of prostate cancer after definitive local therapy. Cancer. 2006 Jul 1;107(1):67-74.

(22.) Beinart G, Rini BI, Weinberg V, Small EJ. Antigen-presenting cells 8015 (Provenge) in patients with androgen-dependent, biochemically relapsed prostate cancer. Clin Prostate Cancer. 2005 Jun;4(1):55-60.

(23.) Kantoff P. Recent progress in management of advanced prostate cancer. Oncology (Williston.Park). 2005 Apr;19(5):631-6.

(24.) Schellhammer PF, Hershberg RM. Immunotherapy with autologous antigen presenting cells for the treatment of androgen independent prostate cancer. World J Urol. 2005 Feb;23(1):47-9.

(25.) Burch PA, Croghan GA, Gastineau DA, et al. Immunotherapy (APC8015, Provenge) targeting prostatic acid phosphatase can induce durable remission of metastatic androgen-independent prostate cancer: a Phase 2 trial. Prostate. 2004 Aug 1;60(3):197-204.

(26.) Eymard JC, Bernard J. Cell therapy and prostate cancer. Bull Cancer. 2003 Aug;90(8-9):734-43.

(27.) Rini BI. Technology evaluation: APC-8015, Dendreon. Curr Opin Mol Ther. 2002 Feb;4(1):76-9.

(28.) Valone FH, Small E, MacKenzie M, et al. Dendritic cell-based treatment of cancer: closing in on a cellular therapy. Cancer J. 2001 Nov;7 Suppl 2S53-S61.

(29.) Small EJ, Fratesi P, Reese DM, et al. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol. 2000 Dec 1;18(23):3894-903.

(30.) Available at: http://online.wsj.com/article/SB117911315709601659.html. Accessed June 21, 2007.

(31.) Available at: http://www.drugs.com/nda/junovan_070509.html. Accessed June 21, 2007.

(32.) Available at: www.hemonctoday.com/200503/frameset.asp?article=autologous.asp. Accessed June 25, 2007.

(33.) Available at: www.investor.dendreon.com/ReleaseDetail.cfm?ReleaseID=164087&Header=IR. Accessed June 22, 2007.

(34.) Burch PA, Breen JK, Buckner JC, et al. Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer. Clin Cancer Res. 2000 Jun;6(6):2175-82.

(35.) Available at: www.hemonctoday.com/scorecards/APC8015.asp. Accessed June 22, 2007.

(36.) Available at: http://professional.cancerconsultants.com/oncology_main_news.aspx?id=38681. Accessed June 22, 2007.

(37.) Higano C, Burch PA, Small EJ, et al. Immunotherapy (APC8015) for androgen independent prostate cancer (AIPC): final progression and survival data from a secon(+) Phase 111 trial. ECCO 13th European Conference, Oct 2005.

PROVENGE[R] IS NOT "THE" MIRACLE DRUG

When reviewing the statistical data on Provenge[R], it is tempting to think that it could be a long awaited "cure" for the second leading cause of cancer death in men. In reality, while Provenge[R] appears to be better than any other drug ever discovered for this common type of cancer, it is not by itself a miraculous "cure."

We at Life Extension view Provenge[R] as a powerful new weapon that could be added to an armamentarium of therapies to provide those with advanced prostate cancer with the best opportunity of achieving a complete response.

Regrettably, the FDA does not consider that innovative oncologists could incorporate Provenge[R] into a multi-modal treatment approach that would provide prostate cancer victims with significantly improved opportunities to conquer their disease. Even though anti-viral drug "cocktails" have enabled those with HIV to live decades longer than they used to, the FDA does not provide cancer patients with the same access to novel drugs that, when used in the proper combination, could result in fewer human beings dying.

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Even if Provenge[R] only extended life by an average of four months, this could provide 10,000 human beings with the opportunity to access a true "magic bullet" future cure for prostate cancer, instead of dying by government edict right before one becomes available.

Provenge[R] by itself was proven to work, but that is meaningless to those whose disease has advanced to a point where they will die before the drug is ever approved under the FDA's new ruling.

DR. STEPHEN STRUM'S EARLY RECOGNITION OF PROVENGE[R]

In the book, A Primer on Prostate Cancer: the Empowered Patient's Guide, published by Life Extension Media, authors Dr. Stephen Strum and Donna Pogliano listed Provenge[R] as one of the promising "treatments on the horizon" in the year 2002.

For those who don't know Dr. Strum, he is a pioneer in the identification and integration of advanced prostate cancer therapies into the clinical setting. Dr. Strum has worked tirelessly with the Life Extension Foundation to enlighten prostate cancer patients of many therapies that are FDA-approved, but that treating oncologists often neglect to administer.

It is sad to say that much of the information in A Primer on Prostate Cancer is still not being routinely used in the clinical setting. For prostate cancer patients seeking information about how to better treat their disease, this meticulously written book is still available by calling 1-800-544-4440. (Cover price: $28.95. Member price: $21.71.)

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
PROVENGE[R] EXTENDS
PROSTRATE CANCER SURVIVAL

Placebo 11%
 n=45

Provenge[R] 34%
 n=82

Men who received the prostate
cancer vaccine Provenge[R] were
three times more likely to survive
for three years, compared with
men who received placebo. (32)

Note: Table made from bar graph.

OVERVIEW OF PROVENGE[R] CLINICAL STUDIES AND RESULTS

STUDY NAME PATIENT NATURE OF
 POPULATION PC

D9905 Phase II, 19 patients; prior ADPC
open label study definitive RP or RT
22,33 followed by PSAR
 with PSA levels
 0.4-6.0 ng/mL

Provenge [R] + 22 patients with ADPC
Avastin [R] PSAR after RP,
(APC8015) 21 RT, or both with
 rising PSA between
 0.4 and 6.0 ng/mL;
 Provenge [R] given at
 weeks 0, 2, and 4;
 Avastin [R] 10mg/kg
 after vaccine and
 every 2 weeks until
 PC progression or
 toxicity.

Phase I/II Open 12 patients with AIPC
Label Study 29 advanced
 metastatic disease
 and heavy
 pretreatment
 including chemo
 and 19 patients
 with non-metastatic
 disease and PSAR
 post ADT. Both
 groups defined as
 AIPC.

Phase I 13 patients with AIPC
Open-Label Study metastatic PC
34

D9901 (APC8015) 127 patients at 19 AIPC; with
Phase III, study sites: 82 progression
randomized study received after ADT; no
of Provenge [R] (with Provenge [R], 45 symptoms.
comparison crossover received placebo;
study); infusions given
presented at ASCO weeks 0, 2, and 4;
2005 Orlando comparison
meeting and published crossover to
in APC8015F (34
JCO5,9,32,35 patients) after
 progression on
 placebo arm.

Update of D9901 See above As above
presented at
Prostate Cancer
Foundation Oct 19-
21, 2006 36

Provenge [R] followed 147 patients AIPC
by Taxotere, [R] randomized to
presented at Provenge [R] vs.
Chemotherapy placebo with crossover
Foundation in 56
Symposium in progressing
NYC 36 patients

D9902A 37 65 pts randomized AIPC; with
 to Provenge [R] progression
 versus 33 placebo after ADT; no
 symptoms.

STUDY NAME RESULTS ADDITIONAL
 INFO

D9905 Phase II, 72% (13 of 18) Of 13 with
open label study evaluable patients increased
22,33 prolonged PSADT PSADT, 5 had
 with 62% increase PSADT > 12
 [4.9 to 7.9 months] (p months and 1
 = 0.09). with PSADT
 increase from
 3.5 to 66.6
 months.

Provenge [R] + Median PSADT in 20 Median time to
Avastin [R] evaluable patients: progression
(APC8015) 21 pre-Rx 6.9 months vs. was 11.2
 12.7 months post-Rx, months and no
 approaching a 90% patients with
 increase in PSADT objective PC
 (p=0.01). 6 patients progression.
 with increase at least Drop in PSA
 200% (range 214- from baseline in
 758%). 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.

Phase I/II Open 3 patients with > 50% Median time to
Label Study 29 decrease in PSA + 3 disease
 more patients with 25- progression
 49% decreases in for phase I
 PSA. No improvements patients = 12
 in bone scans or soft weeks, and
 tissue disease observed. 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.

Phase I 3 of 12 evaluable Median time to
Open-Label Study patients with > 50% disease
34 PSA. 2 of above with progression was
 also in PAP. 135 days after
 registration
 (range, 30-274
 days).

D9901 (APC8015) Time to objective Overall
Phase III, progression (TTP) survival 25.9
randomized study NOT significantly months with
of Provenge [R] (with different, but with Provenge [R]
comparison crossover trend for active Rx vs. 21.4 months
study); arm (p = 0.052). TTP with placebo;
presented at ASCO 11.7 weeks for p=0.01, hazard
2005 Orlando Provenge [R] vs. 10.0 ratio 1.7 and
meeting and published weeks for placebo. 95% confidence
in PSA not used to interval
JCO5,9,32,35 determine TTP. 1.13-2.56.

 At 3 years, 34%
 survival in
 Provenge [R]
 arm vs. 11% in
 placebo arm (p =
 0.005).

 In subset of
 patients with
 immune
 monitoring,
 there was an
 8-fold advan-
 tage in T-cell
 stimulation for
 Provenge [R] vs.
 placebo.

Update of D9901 Median PC
presented at specific
Prostate Cancer survival 35.2
Foundation Oct 19- months with
21, 2006 36 Provenge [R] vs.
 23.5 months with
 placebo; Hazard
 ratio 2.04 for
 PC specific
 survival in
 favor of
 Provenge [R]
 and 1.71 for
 risk of overall
 survival in
 favor of
 Provenge [R].

Provenge [R] followed Median survival 34.5 Cross-over
by Taxotere, [R] months Provenge [R] patients: median
presented at Taxotere [R] vs. 20.2 survival 25.7
Chemotherapy months for placebo months for
Foundation Taxotere [R] placebo APC8015F
Symposium in Taxotere [R]
NYC 36

D9902A 37 Primary endpoint No difference
 TTP, and secondary between
 endpoint overall Provenge [R] vs.
 survival placebo, but
 multivariate
 analysis of 5
 prognostic items
 showed
 Provenge [R] to
 be significant
 (p = 0.023).
 Integrated
 analysis of
 D9901 & D9902A
 (identical
 variables in
 both studies)
 showed median
 survival with
 Provenge [R]
 of 23.2 months
 vs. 18.8 months
 for placebo (p
 = 0.011; HR 1.5).

STUDY NAME SIDE EFFECTS
 AND TOXICITY

D9905 Phase II, Most common side
open label study effects: fever and chills
22,33 (low grade and short
 duration).

Provenge [R] + 4 patients removed
Avastin [R] from study due to
(APC8015) 21 toxicity (congestive
 heart failure,
 gastrointestinal
 hemorrhage,
 cerebrovascular
 ischemia, and
 proteinuria). These are
 side effects attributable
 to Avastin [R].

Phase I/II Open Median time to disease
Label Study 29 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 5 patients with mild
Open-Label Study (grade 1-2) short-lived
34 fever and/or chills. 5
 patients with myalgia,
 pain, and fatigue. One
 patient developed
 grade 3 fatigue.

D9901 (APC8015) Toxicity: rigors (59.8%
Phase III, vs. 8.9%), pyrexia
randomized study (29.3% vs. 2.2%),
of Provenge [R] (with tremor (9.8% vs. 0%),
comparison crossover and feeling cold (8.5%
study); vs. 0%) for Provenge [R]
presented at ASCO vs. placebo.
2005 Orlando
meeting and published
in JCO5,9,32,35

Update of D9901
presented at
Prostate Cancer
Foundation Oct 19-
21, 2006 36

Provenge [R] followed
by Taxotere, [R]
presented at
Chemotherapy
Foundation
Symposium in
NYC 36

D9902A 37

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


Reviewed and critiqued by Stephen B. Strum, MD, FACP (Life Extension Scientific Advisory Board Member)
COPYRIGHT 2007 LE Publications, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2007 Gale, Cengage Learning. All rights reserved.

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Title Annotation:As WE SEE IT
Author:Faloon, William
Publication:Life Extension
Article Type:Report
Geographic Code:1USA
Date:Sep 1, 2007
Words:4470
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