Intrathecal Ziconotide in the Treatment of Refractory Pain in Patients With Cancer or AIDS

TLDR

Ziconotide selectively blocks N‑type voltage‑sensitive calcium channels and is a potential treatment for pain refractory to opioids or associated with intolerable opioid side effects. The study aimed to evaluate the safety and efficacy of intrathecal ziconotide in patients with cancer or AIDS–related pain that is refractory to conventional therapy. In a double‑blind, placebo‑controlled, randomized trial of 111 adults (age 24–85) with cancer or AIDS and VASPI ≥ 50 mm, patients were assigned 2:1 to titrated intrathecal ziconotide or placebo over 5–6 days, followed by a 5‑day maintenance phase and crossover for nonresponders. Intrathecal ziconotide produced a 53.1 % reduction in VASPI versus 18.1 % for placebo (P < .001), with 52.9 % of patients achieving moderate to complete pain relief versus 17.5 % for placebo, and 50 % of ziconotide recipients responding (P = .001), demonstrating clinically and statistically significant analgesia.

Abstract

Ziconotide (formerly SNX-111) selectively blocks N-type voltage-sensitive calcium channels and may be effective in patients with pain that is refractory to opioid therapy or those with intolerable opioid-related adverse effects.To assess the safety and efficacy of intrathecal ziconotide in patients with pain that is refractory to conventional treatment.Double-blind, placebo-controlled, randomized trial conducted from March 12, 1996, to July 11, 1998, at 32 study centers in the United States, Australia, and the Netherlands. Patients were 111 individuals ages 24 to 85 years with cancer or AIDS and a mean Visual Analog Scale of Pain Intensity (VASPI) score of 50 mm or greater. Patients were randomly assigned in a 2:1 ratio to receive ziconotide or placebo treatment.Intrathecal ziconotide was titrated over 5 to 6 days, followed by a 5-day maintenance phase for responders and crossover of nonresponders to the opposite treatment group.Mean percentage change in VASPI score from baseline to the end of the initial titration period.Of the evaluable population, 67 (98.5%) of 68 patients receiving ziconotide and 38 (95%) of 40 patients receiving placebo were taking opioids at baseline (median morphine equivalent dosage of 300 mg/d for the ziconotide group and 600 mg/d for the placebo group; P =.63, based on mean values), and 36 had used intrathecal morphine. Mean (SD) VASPI scores were 73.6 (1.8) mm in the ziconotide group and 77.9 (2.3) mm in the placebo group (P =.18). Mean VASPI scores improved 53.1% (95% confidence interval [CI], 44.0%-62.2%) in the ziconotide group and 18.1% (95% CI, 4.8%-31.4%) in the placebo group (P<.001), with no loss of efficacy of ziconotide in the maintenance phase. Pain relief was moderate to complete in 52.9% of patients in the ziconotide group compared with 17.5% in the placebo group (P<.001). Five patients receiving ziconotide achieved complete pain relief, and 50.0% of patients receiving ziconotide responded to therapy compared with 17.5% of those receiving placebo (P =.001).Intrathecal ziconotide provided clinically and statistically significant analgesia in patients with pain from cancer or AIDS.