Fentanyl Lozenge Effective for Breakthrough Cancer Pain

DENVER--Delivery of fentanyl citrate via the oral mucosa was shown torelieve breakthrough cancer pain within 15 minutes in two thirds of patients,and sometimes within 5 minutes, according to studies presented at the AmericanSociety of Clinical Oncology meeting.

A new drug application for the product, oral transmucosal fentanyl citrate(Actiq), is currently under review by the FDA. If approved, it will bethe first analgesic specifically cleared for a breakthrough pain indication.

The product is made up of a drug matrix (a sweetened lozenge impregnatedwith fentanyl) attached to a handle (see figure),and is designed to facilitate dissolution and absorption of the drug withinthe mouth. This dosage form enables the patient to individually controldrug delivery.

In two titration studies, patients first assessed their current breakthroughpain medication using pain intensity, pain relief, and global performancemeasures. A blinded titration phase followed to identify a dose for eachpatient at which one unit of oral transmucosal fentanyl effectively controlleda typical breakthrough pain episode (doses ranged from 200 µg to1,600 µg). Then, the agent was evaluated at that dosage for two days.

At a poster session, Paul Coluzzi, MD, of The Breast Care and OncologyCare Center, St. Joseph's Medical Plaza, Orange, Calif, presented datafrom 65 cancer pain patients who were receiving a long-acting oral opioidas their around-the-clock medication. At a scientific session, Mary Simmonds,MD, Pennsylvania State University, Hershey, presented her data on 62 patientswho were receiving transdermal fentanyl as their around-the-clock analgesic.

In these two studies, 74% to 76% of patients were titrated to an effectivetransmucosal fentanyl dose. Compared with the patient's baseline evaluationof their previous breakthrough medication, transmucosal fentanyl provedsignificantly better on pain relief scores at 15, 30, and 60 minutes.

Importantly, pain relief was achieved more rapidly with transmucosalfentanyl. Global performance (a measure of overall satisfaction) was alsosignificantly better with the transmucosal drug.

In the California study, only five patients titrated to the highestdose failed to obtain relief, and each had breakthrough pain that was poorlycontrolled with the patient's regular rescue medication at baseline. InDr. Simmonds' study, only four patients failed to find an effective transmucosalfentanyl dose.

"Oral transmucosal fentanyl citrate may be particularly suitedto treat breakthrough pain because of its rapid onset, ease of use, titratability,and noninvasive dosage form," Dr. Simmonds said.

At a scientific session, James Cleary, MD, of the University of WisconsinComprehensive Cancer Center, Madison, reviewed data comparing transmucosalfentanyl with placebo in 130 patients. After dose titration, patients received10 prenumbered randomized dose units--seven containing fentanyl; threeplacebo--for use in breakthrough episodes.

Of those patients titrated to an effective dose, 92 entered the study.Dr. Cleary reported that transmucosal fentanyl provided significantly betteranalgesia than placebo, as measured by pain intensity and pain relief scoresat 15, 30, 45, and 60 minutes. Global performance was also significantlybetter, and patients on the transmucosal drug required less additionalanalgesia for breakthrough pain.

Patients who completed the three trials described above were then screenedfor eligibility to enroll in a long-term safety study. Of those eligible,92% chose to continue using transdermal fentanyl.

At an ASCO poster session, Alan Lyss, MD, Missouri Baptist Cancer Center,St. Louis, reported on 155 patients in the long-term study, treated a meanof 92 days. Treatment was rated as successful in 92% of episodes treated(nearly 39,000 episodes). Global performance was consistently rated above3, indicating very good to excellent relief. There was no trend towarddecreased effectiveness over time, he said, suggesting that significanttolerance to the beneficial effects does not develop with long-term exposure.

The most common side effects of transmucosal fentanyl in all four studieswere the common opioid effects of somnolence, nausea, and dizziness. Theeffects were generally mild and often resolved with continued treatment.