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

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



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


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


In this multicentre open-label longitudinal trial, 30 ?g 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.


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.


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.

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DOI: http://dx.doi.org/10.3747/co.v18i3.732

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ISSN: 1198-0052 (Print) ISSN: 1718-7729 (Online)