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Intrathecal ziconotide ameliorates refractory pain from cancer or AIDS
  By Megan Rauscher
NEW YORK (Reuters Health) - In a randomized, double-blind, placebo-controlled trial, intrathecal ziconotide provided clinically and statistically significant analgesia in patients with refractory pain from cancer or AIDS, investigators report.
Ziconotide (Neurex Pharm, Menlo Park, CA) is a synthetic version of the venom of a marine snail, a selective N-type neuronal calcium channel blocker. It is currently under review by the U.S. Food and Drug Administration and received an approvable letter in June 2000. (See Reuters Health Report June 29, 2000)
In the current study, 111 adult patients with advanced cancer or AIDS and a mean Visual Analog Scale of Pain Intensity (VASPI) score of 50 mm or greater on a scale of 0 to 100 mm, despite systemic or intrathecal analgesics, were randomized to ziconotide or placebo in a 2:1 ratio.
"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," investigators explain in the January 7th issue of The Journal of the American Medical Association.
Mean VASPI scores improved 53.1% in the ziconotide group compared with 18.1% in the placebo group (p < 0.001), with no reduction in efficacy during the maintenance phase, the researchers report.
Pain relief was "moderate to complete" in 52.9% of ziconotide-treated compared with 17.5% of placebo-treated patients. Opioid use fell in the ziconotide group by 9.9% but increased in the placebo group by 5.1%.
"Patients with cancer pain have been undertreated for a long time, and what we've shown is that intrathecal ziconotide can be effective," lead investigator Dr. Peter S. Staats from Johns Hopkins University in Baltimore told Reuters Health.
Side effects seen significantly more often with ziconotide than with placebo -- including somnolence, confusion, urinary incontinence, and fever -- were "easily recognizable and reversible," according to investigators, and their incidence decreased when they lowered the initial dose of the drug and the frequency of titration.
A "high rate" of infection noted in the study is probably due to the poor physiological status of the patients and the use of external catheters, "not to the idiosyncratic effect of the drug," they note. There were 7 cases of meningitis in study subjects, 5 in the ziconotide group, and all occurred among patients with external catheters.
"This drug is not the end-all for all patients but it certainly is one avenue for refractory pain," Dr. Staats said. "A lot of the patients did well on intrathecal ziconotide. I have one patient from the study close to 6 years later who's still doing well with it. Others had side effects," he added.
The researchers are confident that completed and ongoing trials "will better define the long-term risk-benefit profile of this potent analgesic."
JAMA 2004;291:63-70.
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