DENVER--Delivery of 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
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
"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.