for those with severe pain--some relief care of the puffer fish

[Lani]

Tetrodotoxin May Be Effective in Patients With Severe Cancer Pain

NEW YORK (Reuters Health) Aug 31 - Intramuscular injection of tetrodotoxin, a neurotoxin found in puffer fish, is an effective treatment for severe refractory cancer-related pain, according to findings published in the August issue of the Journal of Pain and Symptom Management. The drug is generally well tolerated.

"Cancer pain can usually be well controlled with oral opioids and other standard analgesic interventions," Dr. Neil A. Hagen, of the Tom Baker Cancer Center in Calgary, Alberta, Canada, and colleagues point out. "However, for some patients with severe pain, high doses of current therapies either fail to produce sufficient relief or result in side effects that significantly impair quality of life."

In an open-label, multicenter, dose-escalation study, the researchers examined the safety and efficacy of intramuscular tetrodotoxin, a highly selective sodium channel blocker, in patients with severe, unrelieved cancer pain.

A total of 24 patients underwent 31 courses of treatment at doses ranging from 15 to 90 mcg daily, administered in divided doses. Twenty courses were administered to patients with predominantly neuropathic pain and 11 courses were administered to those with somatic and visceral pain.

All 24 patients experienced adverse events (AEs). A total of 531 AEs were reported. Of these, approximately 26% occurred in the combined two lower-dose groups and 50% occurred in the combined two higher dose groups, suggesting a modest dose relationship.

Nearly all of the treatment-emergent AEs were mild or moderate in intensity and were transient. The most common AEs were paresthesia and hypesthesia. Nausea and other toxicities were generally mild.

However, two patients experienced a serious adverse event, ataxia that resolved within days.

Of the 31 treatments, 17 resulted in clinically meaningful reductions in pain intensity. Pain relief persisted for up to 2 weeks or longer, according to the investigators. "Somatic, visceral, and neuropathic pain could all respond," they note, "but it was not possible to predict which patients were more likely to have an analgesic effect."

The researchers also report that the total daily dosages of opioids were reduced in 12 of 31 treatments (39%) for more than 2 consecutive days. Reductions were made in both breakthrough opioids and daily maintenance dosages.

"Pain is an extraordinarily complex phenomenon," Dr. Hagen's team points out, "and although a dose escalation trial design involving modest numbers of patients can identify adverse effects and clinical benefit, further experience with larger numbers of patients and specific subtypes of pain would be very helpful."

J Pain Symptom Manage 2007;34:171-182.