A multicentre open-label safety and efficacy study of tetrodotoxin for cancer pain.

Abstract

BACKGROUND:

Cancer pain is highly prevalent, and existing treatments are often insufficient to provide adequate relief.

OBJECTIVES:

We assessed the long-term safety and efficacy of subcutaneous tetrodotoxin treatment in reducing the intensity of chronic cancer-related pain.

METHODS:

In this multicentre open-label longitudinal trial, 30 μg tetrodotoxin was administered subcutaneously twice daily for 4 days in a heterogeneous cohort of patients with persistent pain despite opioids and other analgesics. "Responder" was defined as a mean reduction of 30% or more in pain intensity from baseline; and "clinical responder" as some pain reduction, but less than 30%, plus agreement on the part of both the patient and the physician that a meaningful analgesic response to treatment had occurred.

RESULTS:

Of 45 patients who entered the longitudinal trial, 41 had sufficient data for analysis. Of all 45 patients, 21 (47%) met the criteria for "responder" [16 patients (36%)] or "clinical responder" [5 patients (11%)]. Onset of pain relief was typically cumulative over days, and after administration ended, the analgesic effect subsided over the course of a few weeks. No evidence of loss of analgesic effect was observed during subsequent treatments (2526 patient-days in total and a maximum of 400 days in 1 patient). One patient withdrew from the study because of adverse events. Toxicity was usually mild (82%) or moderate (13%), and remained so through subsequent treatment cycles, with no evidence of cumulative toxicity or tolerance.

CONCLUSIONS:

Long-term treatment with tetrodotoxin is associated with acceptable toxicity and, in a substantial minority of patients, resulted in a sustained analgesic effect. Further study of tetrodotoxin for moderate-to-severe cancer pain is warranted.

• Authors: N A Hagen, B Lapointe, M Ong-Lam, B Dubuc, D Walde, B Gagnon, R Love, R Goel, P Hawley, A Ho Ngoc, P du Souich
• Journal: Current oncology (Toronto, Ont.) (Curr Oncol) Vol. 18 Issue 3 Pg. e109-16 (Jun 2011) ISSN: 1718-7729 [Electronic] Switzerland
• PMID: 21655148 (Publication Type: Journal Article)