title: 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.
  
  
  OBJECTIVE
  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.affiliation: Tom Baker Cancer Centre and Departments of Oncology, Clinical Neurosciences, and Medicine, University of Calgary, Calgary, AB. neil.hagen@albertahealthservices.ca
authors.forename: N A
authors.initials: NA
authors.lastname: Hagen
authors.forename: B
authors.initials: B
authors.lastname: Lapointe
authors.forename: M
authors.initials: M
authors.lastname: Ong-Lam
authors.forename: B
authors.initials: B
authors.lastname: Dubuc
authors.forename: D
authors.initials: D
authors.lastname: Walde
authors.forename: B
authors.initials: B
authors.lastname: Gagnon
authors.forename: R
authors.initials: R
authors.lastname: Love
authors.forename: R
authors.initials: R
authors.lastname: Goel
authors.forename: P
authors.initials: P
authors.lastname: Hawley
authors.forename: A Ho
authors.initials: AH
authors.lastname: Ngoc
authors.forename: P
authors.initials: P
authors.lastname: du Souich