Oral transmucosal fentanyl citrate: randomized, double-blinded, placebo-controlled trial for treatment of breakthrough pain in cancer patients.

BACKGROUND Patients with cancer frequently experience episodes of acute pain, i.e., breakthrough pain, superimposed on their chronic pain. Breakthrough pain is usually treated with short-acting oral opioids, most of which provide some relief after 15-20 minutes, with peak effects after 30-45 minutes. Oral transmucosal fentanyl citrate (OTFC), a unique formulation of the opioid fentanyl, has been shown to provide meaningful pain relief within 5 minutes in patients following surgery. We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of OTFC for cancer-related breakthrough pain. METHODS Patients who were 18 years of age or older, receiving the equivalent of at least 60 mg oral morphine or at least 50 microg transdermal fentanyl per day for chronic cancer-related pain, and experiencing at least one episode of breakthrough pain per day were studied. After titration to an effective OTFC dose, subjects were given 10 randomly ordered treatment units (seven OTFC units and three placebo units) in the form of identical lozenges. If acceptable pain relief was not achieved within 30 minutes, subjects were instructed to take their previous breakthrough pain medication (i.e., rescue medication). Pain intensity, pain relief, and use of rescue medication were evaluated at 15-minute intervals over a 60-minute period. RESULTS Eighty-nine of 92 patients who received the randomized treatment were assessable (i.e., treated with at least one unit of OTFC and one unit of placebo). OTFC produced significantly larger changes in pain intensity and better pain relief than placebo at all time points (two-sided P<.0001). Episodes treated with placebo required the use of rescue medication more often than episodes treated with OTFC (34% versus 15%; relative risk = 2.27; 95% confidence interval = 1.51-3.26; two-sided P<.0001). CONCLUSIONS OTFC appears effective in the treatment of cancer-related breakthrough pain.