DENVER--Delivery of fentanyl(Drug information on fentanyl) citrate via the oral mucosa was shown to relieve breakthrough cancer pain within 15 minutes in two thirds of patients, and sometimes within 5 minutes, according to studies presented at the American Society 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 be the first analgesic specifically cleared for a breakthrough pain indication.
The product is made up of a drug matrix (a sweetened lozenge impregnated with fentanyl) attached to a handle (see figure), and is designed to facilitate dissolution and absorption of the drug within the mouth. This dosage form enables the patient to individually control drug delivery.
In two titration studies, patients first assessed their current breakthrough pain medication using pain intensity, pain relief, and global performance measures. A blinded titration phase followed to identify a dose for each patient at which one unit of oral transmucosal fentanyl effectively controlled a typical breakthrough pain episode (doses ranged from 200 µg to 1,600 µg). Then, the agent was evaluated at that dosage for two days.
At a poster session, Paul Coluzzi, MD, of The Breast Care and Oncology Care Center, St. Joseph's Medical Plaza, Orange, Calif, presented data from 65 cancer pain patients who were receiving a long-acting oral opioid as their around-the-clock medication. At a scientific session, Mary Simmonds, MD, Pennsylvania State University, Hershey, presented her data on 62 patients who were receiving transdermal fentanyl as their around-the-clock analgesic.
In these two studies, 74% to 76% of patients were titrated to an effective transmucosal fentanyl dose. Compared with the patient's baseline evaluation of their previous breakthrough medication, transmucosal fentanyl proved significantly better on pain relief scores at 15, 30, and 60 minutes.
Importantly, pain relief was achieved more rapidly with transmucosal fentanyl. Global performance (a measure of overall satisfaction) was also significantly better with the transmucosal drug.
In the California study, only five patients titrated to the highest dose failed to obtain relief, and each had breakthrough pain that was poorly controlled with the patient's regular rescue medication at baseline. In Dr. Simmonds' study, only four patients failed to find an effective transmucosal fentanyl dose.
"Oral transmucosal fentanyl citrate may be particularly suited to 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 Wisconsin Comprehensive Cancer Center, Madison, reviewed data comparing transmucosal fentanyl with placebo in 130 patients. After dose titration, patients received 10 prenumbered randomized dose units--seven containing fentanyl; three placebo--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 better analgesia than placebo, as measured by pain intensity and pain relief scores at 15, 30, 45, and 60 minutes. Global performance was also significantly better, and patients on the transmucosal drug required less additional analgesia for breakthrough pain.
Patients who completed the three trials described above were then screened for 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 mean of 92 days. Treatment was rated as successful in 92% of episodes treated (nearly 39,000 episodes). Global performance was consistently rated above 3, indicating very good to excellent relief. There was no trend toward decreased effectiveness over time, he said, suggesting that significant tolerance to the beneficial effects does not develop with long-term exposure.
The most common side effects of transmucosal fentanyl in all four studies were the common opioid effects of somnolence, nausea, and dizziness. The effects were generally mild and often resolved with continued treatment.