Puffer Fish Toxin Could Change
the Treatment of Cancer Pain
By Claire Sowerbutt

For patients with cancer, who are suffering from pain that no longer responds to currently available drugs, there is a new pain medication being tested that could revolutionize therapy. It is a neurotoxin called tetrodotoxin (Tectin™), and it comes from the puffer fish. Originally developed by the Vancouver based biopharmaceutical company International Wex Technologies for the treatment of heroin addiction, Tectin™ has shown such promise in early clinical cancer pain trials that it is now in a pivotal phase IIb/ III study - the final phase needed before applying to Health Canada for market approval.

The pain associated with cancer and its treatments can be overwhelming. The American Pain Society recently noted that pain is experienced by as many as 60-90% of patients with advanced disease. Unfortunately, in many cases, the medications used to treat the pain lose their effectiveness. Previous clinical trials of Tectin™ have shown it to be effective at relieving pain in patients who have what is called 'refractory cancer pain' - pain that no longer responds to existing medications. The phase IIa results showed 72% of cancer patients received clinically meaningful pain relief.

Furthermore, Tectin™, unlike many pain medications used in refractory cancer pain, is non drowsy, and non addictive. In some patients it has provided pain relief for up to 15 days at a time. To-date, the most common side effects seen with the toxin are tingling of the lips and tongue, which doesn't last. Dr. Doreen Oneschuk of the Palliative Care Unit at the Grey Nuns Community Hospital in Edmonton, who was involved in the phase II study of tetrodotoxin and is involved in the current trial said, "The previous study had indicated a partial or moderate benefit. It is very promising. The side effects were minor, paraesthesia, numbness, and tingling sensations. On the whole, it [Tectin™] was quite well received."

Tetrodotoxin is contained in minute amounts in sushi prepared from puffer fish. In Japan the puffer fish is a culinary delicacy, and can only be prepared by specially trained and licensed chefs. The poison itself comes from the liver and gonads of the fish, and it works by blocking sodium channels. If taken in large enough amounts it causes temporary respiratory paralysis, but Wex International Technologies have purified the compound to pharmaceutical grade, and can obtain 600 doses from a single fish. "We do make it very clear that while it is a toxin it is given in very small concentrations to ensure safety," said Dr. Oneschuck. The puffer fish themselves are raised on fish farms for consumption - Wex uses the waste products from the yellow fin puffer fish. - PULSEMED.ORG

PUFFER FISH TOXIN FOR CANCER PAIN
By Dr. Howard Cohen, MD

Howard Cohen, MD, is the president of Dallas Mind/Body Medicine. He was the cofounder, Fellowship Director, then Clinical/Research Director of the Texas Pain Medicine Clinic. Dr. Cohen obtained his certification as a Diplomate in Psychiatry from the American Board of Psychiatry & Neurology in 1991. He became a Diplomate in Pain Medicine from the American Board of Pain Medicine in 1992. He further received Subspecialty certifications from the American Board of Psychiatry & Neurology in Geriatric Psychiatry (1992), Addiction Psychiatry (1993), and Pain Medicine (2001). D. Cohen has lectured at the University of Texas Southwestern Medical School and the Graduate School of Nursing at the University of Texas. He has published in the field of pain medicine and addiction and is currently a consultant to several pharmaceutical corporations and technology companies.

Undertreatment of cancer pain continues to be a clinical problem as more effective therapies lead to patients living longer with unrelieved pain. The American Pain Society notes that pain is experienced by 60-90% of patients with advanced cancer; many patients silently tolerate unrelieved pain. A new treatment that shows promise in preliminary testing may allow palliative care professionals new options in treating patients with cancer pain resistant to current treatments.

Tetrodotoxin, the toxin of the puffer fish, has been purified by a Vancouver based biopharmaceutical company and has shown to be safe and effective in relieving treatment resistant cancer pain. Dr. Neil Hagen presented final results of a phase IIa open label, multicenter trial of tetrodotoxin at the Joint Scientific Meeting of the American and Canadian Pain Societies meeting in Vancouver. In this study, 22 subjects with treatment resistant cancer pain were treated twice a day for four days. Of the 22 subjects involved in the study 72% reported a meaningful fall in pain levels. Patients exhibited a gradual onset of pain relief beginning on or about the third day of treatment and lasted many days after the final injection. Some patients experienced significant pain relief for up to two weeks.

Typical side effects included tingling of the lips and tongue.

Tetrodotoxin is the poison contained in minute amounts of sushi prepared from the puffer fish. In Japan, specially trained and licensed chefs prepare the delicacy. The ancient Chinese and Japanese were aware of the toxin contained in puffer fish and used the non-poisonous parts of the fish as a general health tonic. Prior to WW II Japanese researchers experimented with crude puffer fish extract to treat migraines and menstrual cramps. Puffer fish have fascinated observers around the world for centuries. Symbols of the fish have been identified on Egyptian tombs dated 2700 BC. The poison, a sodium channel blocking compound that causes a temporary respiratory paralysis, is chiefly contained in the liver and gonads of the puffer fish and each fish can provide up to 660 doses of the medicine. The Vancouver company has extracted the waste products of yellow fin puffer fish (Fugu Xanthopterus) and purified them to create a drug safe for human use. In overseas clinical trials, the drug has also been shown to reduce withdrawal symptoms in heroin addicts.

Based on the initial positive studies, a 150 patient phase IIb/III trial is currently underway in 25 cities across Canada. Results are expected in 2005, and if trials go well the company is optimistic the drug will be widely available by 2006.