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Aptosyn (Exisulind) Stabilizes Prostate Cancer

But is it so new?

NEW YORK, NY, May 7, 2000 - Aptosyn (exisulind, or sulindac sulfone) may be useful as a treatment for men with advanced prostate cancer. Columbia Presbyterian researchers say that for patients with progressive recurrent prostate cancer, the drug may stabilize the disease.

Principal investigator Dr. Erik Goluboff, presenting results at the annual meeting of the American Urological Association in Atlanta, Ga., on May 1, said Aptosyn increases the rate of programmed cell death in cancer cells without damaging normal cells. "This means that the cancerous cells die and can no longer keep dividing and multiplying, which stops the cancer from growing."

Dr. Goluboff says Aptosyn is one of a new class of compounds called selective apoptotic anti-neoplastic drugs (SAANDs). SAANDs inhibit cyclic GMP phosphodiesterase and selectively induce apoptosis (programmed cell death) in abnormally growing precancerous and cancerous cells.

SAANDs do not induce apoptosis in normal cells, so they do not produce most of the adverse reactions or serious side effects normally associated with chemotherapeutic agents used to treat cancer, Goluboff says.

"Our study showed that exisulind can safely and significantly arrest tumor growth with a minimum of side effects," says Dr. Goluboff. "The results provide evidence that the drug may be an effective alternative to current treatment options."

Previous studies in mice showed that Aptosyn inhibits the growth of prostate cancer by 80 percent to 90 percent. In a related study of human patients, researchers found that the drug also caused regression in the growth of precancerous colonic polyps, a condition that often leads to colon cancer.

This trial followed 96 prostate cancer patients, who already had their prostate glands removed, for 12 months. All had rising prostate specific antigen (PSA) levels indicating recurrent disease. Half received exisulind and half were given dummy pills (placebo). The researchers measured the active drug's ability to slow or halt disease progression by following patients' PSA levels. High levels of PSA are associated with more aggressive disease.

Imaging tests were performed before and after the study. All of the men were classified into risk groups with no statistical difference in age, race, and weight. The study showed a significant decrease in the rate of rise in PSA in patients given exisulind compared with placebo.

Research indicates that exisulind reduced the growth of prostate cancer in men with progressive, recurrent disease, thereby possibly providing long-term disease control with low incidence of side effects otherwise unattainable for this patient group," says Dr. Goluboff.

Dr. Goluboff cautions that more research needs to be conducted to determine long-term effects in these patients and in other groups of patients with prostate cancer.

The study was funded by Cell Pathways Inc., developer of the drug Exisulind.


Cell Pathways, Inc. received patent for SAANDs drug CP46 September 1999

Cell Pathways, Inc. pages on:

Aptosyn (exisulind)

Geriatric Review page on Clinoril (sulindac)

Clinoril (sulindac) overdose (Medline Plus)

Prostate Cancer clinical trials of exisulind

Abstract of earlier study by the same team:
Urology 1999 Feb;53(2):440-5 Exisulind (sulindac sulfone) suppresses growth of human prostate cancer in a nude mouse xenograft model by increasing apoptosis. Goluboff ET, et al Department of Urology, and Comprehensive Cancer Center, School of Medicine, Columbia University, New York, New York, USA.

Biochem Pharmacol 1999 Oct 1;58(7):1097-107 Sulindac derivatives inhibit growth and induce apoptosis in human prostate cancer cell lines. Lim JT, et al Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

In tests that showed that Sulindac sulfone shrinks rectal polyps, the drug was given for six months. Liver damage, the dose-limiting toxicity, occurred at 400 mg twice a day.

Adv Exp Med Biol 1999;470:45-53 Sulindac sulfone induced regression of rectal polyps in patients with familial adenomatous polyposis. Stoner GD, et al Ohio State University School of Public Health, Columbus, USA.

A different view of how sulindac might work against cancer cells:

Int J Tissue React 1998;20(3):85-9 Inhibition of angiogenesis by sulindac and its sulfone metabolite (FGN-1): a potential mechanism for their antineoplastic properties. Skopinska-Rozewska E et al Department of Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.

Ralph Valle, cofounder of PCAN

Ralph Valle, a chemist, is a leader of Prostate Cancer Action Network (PCAN).

"I am amazed at the hype ... Exisulind has been around for almost 20 years. Merck markets something called Clinoril (known as Sulindac USP). Well, guess what? When one takes Clinoril orally, it becomes what they call Exisulind or sulindac sulfone. Clinoril is a NSAID and now they call Exisulind a SAAND and probably charge an arm and a leg. Generic Sulindac is $20 for 60 x 200 mg tablets. The recommended daily dose is 400 mg/day. Sulindac was one of the NSAIDs that prevented polyposis and the onset of colon cancer."

Ralph's comments sparked a discussion at Raging Bull discussion Board for Cell Pathways stock investors and this email to psa-rising.

From: Art Lange
Subject: Article on Exisulind in PSA Rising
Date sent: Thu, 8 Jun 2000 00:21:30 -0700

Thank you for the nice article about Exisulind . . . which describes the results of the prostate clinical trial for Aptosyn.

I was a bit troubled by the comments of Ralph Valle who was quoted in the sidebar and who seems to miss the point that Sulindac has two metabolites. One is Sulindac Sulphone - Exisulind (Aptosyn) and the other is Sulindac sulfide which he does not mention. The compound Sulindac sulfide has the NSAID activity with its COX-1 inhibitor activity, and according to Merck, is the active ingredient of Sulindac (Clinoril). Unfortunately for most patients on Sulindac, there are usually severe gastric distress side effects from long term use of Clinoril because of the Sulindac sulfide COX-1 inhibitor metabolite. The excitement about Aptosyn is that it can be taken for long periods of time with no gastric side effects. If the off-patent Sulindac which is available for low cost turns out to be too toxic to the patient, then the patient can take Aptosyn (after FDA approval). Cell Pathways has publicly stated that the patient cost for Aptosyn will be around $2000 to $2500 per year.

This feedback pushed us to dig out more background.

As Ralph says, Clinoril (sulindac) is a generic non-steroidal anti-inflammatory agent drug (NSAID),. It has been used since the 1970's for arthritis. Like all such drugs it has side effects, especially for older patients.

Geriatric Drug Review says that Clinoril (sulindac) "has been shown to cause a significantly larger number of gastrointestinal complications when compared to other NSAID's (non-steroidal anti-inflammatory drugs).... It is important to note that Clinoril (Sulindac) may be less likely to cause renal toxicity when compared to other NSAID's."

Cell Pathways, Inc. filed a New Drug Application for the metabolite of sulindac in 1999, giving it the trade name Aptosyn (exisulind).

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