ORLANDO-European researchers have shown that transdermal fentanyl (Duragesic) is as effective as sustained-release morphine and better tolerated when given to strong-opioid-naïve patients with chronic cancer pain, according to a poster presented at the American Society of Clinical Oncology’s 38th Annual Meeting (abstract 1506).
ORLANDOEuropean researchers have shown that transdermal fentanyl (Duragesic) is as effective as sustained-release morphine and better tolerated when given to strong-opioid-naïve patients with chronic cancer pain, according to a poster presented at the American Society of Clinical Oncology’s 38th Annual Meeting (abstract 1506).
"We showed that it is safe and effective to go straight from weak opioids to transdermal fentanyl or sustained-release morphine in this population," said Dr. Carol Davis, consultant in palliative medicine and director of research, Countess Mountbatten House, Moorgreen Hospital, Southampton, UK.
Dr. Davis and her colleagues at the Free University of Amsterdam pooled data from two open-label, randomized, parallel, 4-week studies enrolling 312 patients with chronic cancer pain; 170 were 65 years of age or older.
"All were on full-dose weak opioids," Dr. Davis said. "Instead of titrating to immediate-release morphine, we randomized straight from weak opioids to 30 mg of sustained-release morphine every 12 hours or 25 µg/h transdermal fentanyl every 72 hours." Of the 312 patients, 159 received fentanyl and 153 morphine. Patients were assessed at baseline, day 7, and day 28.
Patients in both arms were given gradually higher doses as needed to obtain pain control. The mean maximum dose of transdermal fentanyl was 65 µg/h (range, 25 to 400 µg/h). Sustained-release morphine dosages were increased by 30% to 50% after a minimum of 12 hours. The mean maximum dose was 97 mg (range, 30 to 400 mg).
Both groups were given immediate-release morphine as rescue medicine. More patients in the transdermal fentanyl arm needed breakthrough medication, possibly due to the low starting dose. "Several prior studies have shown that the conversion table for switching patients to transdermal fentanyl may be too conservative," Dr. Davis said.
Pain was the same in both arms, as rated by patients in diaries and weekly assessments, she said. However, more patients from the morphine arm than the fentanyl arm withdrew from the study (37% vs 14%). The withdrawal rates in the elderly subpopulation were 41% and 11%, respectively. Most withdrew within 1 to 2 weeks of starting the study.
"Withdrawal was mainly due to constipation," Dr. Davis said. "Other reasons were CNS-related side effects such as drowsiness, confusion, and hallucinations." At day 7, 61% of patients receiving morphine were constipated, compared with 41% on fentanyl. At the end of the study, the rates were 43% and 34%, respectively. The number of patients using laxatives was similar in both cohorts.
Of the patients receiving fentanyl, 64% scored side effects as "very good" or "good" as assessed by investigators, compared with 48% in the morphine arm. In the elderly subpopulation, the percentages were 68% and 44%, respectively.
Nausea, drowsiness, constipation, and vomiting were the most frequent adverse events, with CNS-related events more common in the elderly, most notably in the morphine arm, Dr. Davis said. However, dizziness was more pronounced in the patients receiving fentanyl.
Progression of disease, aggravated condition, pneumonia, and dyspnea were the most common serious adverse events. Serious adverse events were seen in 32% of the fentanyl arm and 36% of the morphine arm.
She concluded that, in the 312 patients recruited to these studies, both regimens were safe and effective in the general population and the elderly subpopulation. In the UK, transdermal fentanyl is more expensive than sustained-release morphine, but considering the greater side effects with morphine, it may be a false economy, Dr. Davis indicated.
"The pain was the same, both regimens were safe, but the significant difference is seen in side effects and the number of patients who withdrew," she said. "The health economics are interesting, since you must consider the expense of patients needing treatment for constipation, including rectal intervention, and fewer patients were constipated in the fentanyl arm. Other researchers have shown that the cost of transdermal fentanyl relative to controlled-release morphine sulfate in the UK becomes unimportant when you also look at the cost of treating the side effects."