Tetrodotoxin safe, effective for moderate to severe cancer pain

April 29, 2008

NEW YORK (Reuters Health) - Tetrodotoxin, a sodium channel blocker found in several tetraodon pufferfish may relieve moderate to severe cancer pain, according to findings published in the April issue of the Journal of Pain and Symptom Management.

Dr. Neil A. Hagen, of the University of Calgary, Alberta, Canada, and colleagues examined the safety and efficacy of tetrodotoxin (TTX) in 82 patients with moderate to severe, treatment-resistant cancer pain in a multicenter randomized, placebo-controlled study.

Tetrodotoxin was administered subcutaneously over days 1 to 4. The patients were seen again for further safety and efficacy assessments on days 5, 8, and 15. They were then seen every 2 weeks until pain returned. The primary endpoint was the proportion of responders, defined by a 30% or greater reduction in pain intensity.

Analgesic outcome data were available for 77 patients. The team found that 16 of 38 patients assigned to TTX (42%) and 12 of 39 assigned to placebo (31%) were classified as responders. The difference was not statistically significant, at p = 0.425.

However, an exploratory post hoc analysis suggested that there is a robust analgesic response if a composite endpoint is used, including either a reduction in pain by 30% or a fall in opioid consumption greater that 50%, plus a 30% or greater improvement in quality of life.

"The time course of the apparent analgesic response to TTX seen within this study had a similar pattern to what has been described previously: There was an additive analgesic effect until day 4 or 5, the effect peaked around day 10, and then became less after that time, wearing off 2 weeks or longer after the drug was first administered," Dr. Hagen's team reports.

Most patients reported mild sensory side effects, including tingling around the mouth or numbness. Most patients did not experience additional toxicity. One patient was discontinued due to moderately severe ataxia.