New Study Suggests Artificial Sweetener Causes Cancer in Rats at Levels Currently Approved for Humans

Report in Environmental Health Perspectives calls for reevaluation of acceptable limits of aspartame consumption

November 17, 2005 [Research Triangle Park, NC] ] A statistically significant increase in the incidence of malignant tumors, lymphomas and leukemias in rats exposed to varying doses of aspartame appears to link the artificial sweetener to a high carcinogenicity rate, according to a study accepted for publication today by the peer-reviewed journal Environmental Health Perspectives (EHP).

The authors of the study, the first to demonstrate multipotential carcinogenic effects of aspartame administered to rats in feed, called for an “urgent reevaluation” of the current guidelines for the use and consumption of this compound.

“Our study has shown that aspartame is a multipotential carcinogenic compound whose carcinogenic effects are also evident at a daily dose of 20 milligrams per kilogram of body weight (mg/kg), notably less than the current acceptable daily intake for humans,” the authors write. Currently, the acceptable daily intake for humans is set at 50 mg/kg in the United States and 40 mg/kg in Europe.

Aspartame is the second most widely used artificial sweetener in the world. It is found in more than 6,000 products including carbonated and powdered soft drinks, hot chocolate, chewing gum, candy, desserts, yogurt, and tabletop sweeteners, as well as some pharmaceutical products like vitamins and sugar-free cough drops. More than 200 million people worldwide consume it. The sweetener has been used for more than 30 years, having first been approved by the FDA in 1974. Studies of the carcinogenicity of aspartame performed by its producers have been negative.

Researchers administered aspartame to Sprague-Dawley rats by adding it to a standard diet. They began studying the rats at 8 weeks of age and continued until the spontaneous death of each rat. Treatment groups received feed that contained concentrations of aspartame at dosages simulating human daily intakes of 5,000, 2,500, 500, 100, 20, and 4 mg/kg body weight. Groups consisted of 100 males and 100 females at each of the three highest dosages and 150 males and 150 females at all lower dosages and controls.

The experiment ended after the death of the last animal at 159 weeks. At spontaneous death, each animal underwent examination for microscopic changes in all organs and tissues, a process different from the aspartame studies conducted 30 years ago and one that was designed to allow aspartame to fully express any carcinogenic potential.

The treated animals showed extensive evidence of malignant cancers including lymphomas, leukemias, and tumors at multiple organ sites in both males and females. The authors speculate the increase in lymphomas and leukemias may be related to one of the metabolites in aspartame, namely methanol, which is metabolized in both rats and humans to formaldehyde. Both methanol and formaldehyde have shown links to lymphomas and leukemias in other long-term experiments by the same authors.

The current study included more animals over a longer period than earlier studies. “In our opinion, previous studies did not comply with today’s basic requirements for testing the carcinogenic potential of a physical or chemical agent, in particular concerning the number of rodents for each experimental group (40-86, compared to 100-150 in the current study) and the termination of previous studies at only 110 weeks of age of the animals,” the study authors wrote.

The authors of the study were Morando Soffritti, Fiorella Belpoggi, Davide Degli Esposti, Luca Lambertini, Eva Tibaldi, and Anna Rigano of the Cesare Maltoni Cancer Research Center, Oncology Ramazzini Foundation of Environmental and Environmental Sciences, Bologna, Italy. Funding for the research was provided by the Oncology Ramazzini Foundation of Environmental and Environmental Sciences, Bologna, Italy. The article is available free of charge at http://ehp.niehs.nih.gov/docs/2005/8711/abstract.html.

EHP is published by the National Institute of Environmental Health Sciences (NIEHS), part of the U.S. Department of Health and Human Services. EHP EHP is an Open Access journal. More information is available online at http://www.ehponline.org/. Brogan & Partners Convergence Marketing handles marketing and public relations for EHP, and is responsible for creation and distribution of this press release.

As reported, A Protein That Helps Maintain Vitamin E Levels Suppresses Prostate Cancer, University of Rochester Medical Center researchers have found an organic protein in the body, a protein, that helps prostate cancer cells retain vitamin E. This helps vitamin E to limit the growth of the cancer.

This protein, which they call scientists have named alpha tocopherol associated protein, or TAP, suppresses growth of the cancer by disrupting an important signaling pathway in prostate cancer cells.

A reader asks, for men with prostate cancer would it help to take a high quality vitamin E pill?

We don’t really know. Last year a controversial study from Johns Hopkins found that, especially in older people, consumption of current maximum dose of vitamin E was associated with a higher death rate.

Our friend in Israel, Lenny Hirsch, has been fighting a lonely battle to try to get the health plan in his country to provide men with advanced prostate cancer a chance to receive Taxotere (docetaxel). Taxotere is the only chemotherapy drug so far proven to extend the lives of men with advanced metastatic prostate cancer. In Israel and in some European countries many men are not diagnosed until the disease has already spread outside the prostate — and then, as Lenny describes in his article “Sad Day,” they are not even able to receive chemotherapy.

Well, it’s no better in Scotland. Prostate cancer affects one in 15 men in Scotland. It is the UK’s most common form of male cancer and in the UK it has a much higher death rate than in the USA. It affects more than 30,000 UK men each year, killing 10,000 – at least one per hour. Now men in Scotland suffering from advanced prostate cancer have been told they cannot receive Taxotere.

“Men in Scotland with prostate cancer will not receive a life-prolonging drug on the NHS because it is too expensive,” BBC reports. They mean Taxotere.

Dendreon Announces FDA Grants Fast Track Status for Provenge

Update March 28:
FDA Committee to Review Provenge, Questions raised. March 29

Earlier:
Dendreon’s Phase 3 Trial Shows Provenge Vaccine Extends Survival in Patients with Advanced Prostate Cancer Oct 28, 2004

Meanwhile in Europe:
Dendreon’s Second Randomized Phase 3 D9902A Trial of Provenge Extends Survival in Patients with Advanced Prostate Cancer

PARIS, FRANCE, October 31, 2005 – Dendreon Corporation (Nasdaq: DNDN) today announced that final results of its second Phase 3 study (D9902A) of PROVENGE® (sipuleucel-T), the Company’s investigational active cellular immunotherapy for the treatment of prostate cancer, were presented here today during a late-breaking clinical trials session at ECCO 13-the European Cancer Conference. Researchers concluded that these results are consistent with the results from the Company’s first Phase 3 study (D9901). The Company recently announced plans to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) to market PROVENGE based on discussions of these data with the FDA.

“The combined data from the trials of PROVENGE versus placebo demonstrate that active immunotherapy favorably impacts survival in men with asymptomatic, metastatic, androgen-independent prostate cancer,” reported Celestia S. Higano, M.D., director and associate professor of the Genitourinary Oncology Clinical Research Group at the University of Washington, Seattle, who presented the data. “Given the favorable side effect profile, PROVENGE may provide a useful alternative for men prior to initiating chemotherapy.”
Study Results

NEW YORK (Reuters Health) Sept 12 – Treatment with vitamin C or ascorbate at high levels, which can be attained if administered intravenously, can selectively destroy cancer cells, new research indicates.

Prostate cancer patients are lobbying the FDA for approval of Abbot’s oral anti-cancer drug Xinlay (atrasentan), but the FDA is not impressed with the drug.

Abbott Laboratories Inc. did not provide clear evidence of effectiveness for Xinlay, U.S. Food and Drug Administration staff said in a preliminary report on Monday.

Studies of Xinlay also raised “serious cardiovascular safety issues,” the FDA staff said in a report posted on the FDA’s Web site.

In the only trial sufficient to evaluate for approval, Xinlay “does not demonstrate any clear evidence of clinical efficacy” in prostate cancer that has failed to respond to standard hormone therapy, the FDA staff report said.

Abbott, in a separate summary on the FDA Web site, said “the weight of evidence suggests that (Xinlay) provides measurable clinical benefit with a manageable safety profile.”

A panel of experts from outside the FDA is scheduled to decide Tuesday whether to recommend Xinlay for approval. The committee will consider the FDA staff comments, as well as arguments from Abbott.

FDA’s Oncologic Drugs Advisory Committe hearing in Washington, DC on Abbott Lab’s application for approval of Xinlay (Atrasentan) will be held Sept 13. Details for this and other drug applications scheduled for hearings on 13th and 14th, below.

Center: CDER

Date and time:
September 13, 2005, 8:00 a.m. – 5:00 p.m.
September 14, 2005, 8:00 a.m. – 5:00 p.m.

Location:
Holiday Inn
The Ballrooms
8120 Wisconsin Ave.
Bethesda, MD

Open Public Hearing: Oral presentations from the public will be scheduled
between approximately 10:30 a.m. to 11 a.m., and 2:30 p.m. to 3 p.m. on both
September 13 and 14, 2005.

Agenda:
On September 13, 2005, the committee will discuss the following: (1) new drug application (NDA) 21-491, proposed trade name XINLAY (atrasentan hydrochloride) Capsules, Abbott Laboratories, proposed indication for the treatment of men with metastatic hormone-refractory prostate cancer; and (2) NDA 21-743, S003, TARCEVA (erlotinib) TABLETS, OSI Pharmaceuticals Inc., proposed indication for the first-line treatment, in combination with gemcitabine, of patients with locally advanced, unresectable or metastatic
pancreatic cancer.

On September 14, 2005, the committee will discuss the following: (1) NDA 21-880, proposed trade name REVLIMID (lenalidomide), Celgene Corp., proposed indication for the treatment of patients with transfusion-dependent anemia due to low-or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities; and (2) NDA 21-877, proposed trade name ARRANON (nelarabine) Injection, GlaxoSmithKline, proposed indication for the treatment of
patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to, or has relapsed with, at least two chemotherapy regimens.

Background material and meeting information will become available no later than one business day before each meeting day (Simply scroll down to the appropriate committee heading).

Procedure (Open Public Hearing):
Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee. Written submissions may be made to the contact person by September 2, 2005. Oral presentations from the public will be scheduled between approximately 10:30 a.m. to 11 a.m., and 2:30 p.m. to 3 p.m. on both days. Time allotted for each presentation may be limited. Those desiring to make formal oral presentations should notify the contact person before September 2, 2005, and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation. Persons attending FDA’s advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets.

FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact Johanna Clifford at 301-827-7001, at least 7 days in advance of the meeting.

Contact Person:
Johanna M. Clifford, Center for Drug Evaluation and Research (HFD-21), Food and Drug Administration, 5600 Fishers Lane, (for express delivery, 5630 Fishers Lane, Rm. 1093) Rockville, MD 20857, 301-827-7001, FAX: 301-827-6776, e-mail: [email protected]

Advisory Committee Telephone Information Line:
Please call the Information Line for up-to-date information on this meeting,
1-800-741-8138 (301-443-0572 in the Washington, DC area), code 3014512542.

NPCC Suspends Regular Screenings, Lends Support to Hurricane Survivors
A big purple vehicle identified with the fight against cancer is now in the race to save lives in New Orleans.

The Drive Against Prostate Cancer, the world’s most successful mobile prostate cancer screening vehicle (over 35,000 tests in four years), has switched operations to help the survivors of Hurricane Katrina. Full Story “Upfront”

ASCO – Hurricane Katrina Message Board
Date: September 07, 2005, 01:48 AM
From: Physicians Relief Org.
Location: Baton Rouge, LA

We have four physicians in the area and can provide transportation for patients needing to reach oncology practices to continue ongoing treatment. Please call us at 434-227-6900 if the need arises.

The Drive Against Prostate Cancer is headed to Louisiana as soon as we get a
location from the command center. The vehicle will be used for general
medical care. We are doing what we can to help during the crisis. Prostate
Cancer Awareness Month is about saving lives, we are just doing it a little
differently this year. The next prostate cancer screening event with the
Drive will be at Cruisin’ for a Cure in California on September 23 and 24.

–Skip

Skip Lockwood
Executive Vice President and COO
National Prostate Cancer Coalition