Once-Daily Sustained-Release Morphine Effective for Cancer Pain

ADELAIDE, Australia—A sustained-release morphine formulation that can be administered once or twice a day (Kadian) showed similar efficacy and safety to a standard twice-daily morphine formulation (MS Contin) in a multicen-ter, placebo-controlled US study of cancer pain patients, sponsored by the Australian manufacturers of Kadian.

Kadian consists of polymer-coated morphine sulfate pellets in a gelatin capsule and is designed for once- or twice-daily administration.

Moderate to Severe Cancer Pain

The study population consisted of patients with moderate to severe cancer pain who had been titrated to adequate analgesia with immediate-release morphine. Patients whose pain stabilized were then randomized to one of three treatments for seven days: Kadian capsules every 24 hours, with placebo given after 12 hours; Kadian capsules every 12 hours; and MS Contin tablets every 12 hours. Immediate-release morphine was used for breakthrough pain. Of 172 patients, 152 completed the final day assessment.

The time to re-medication (the next dose whether rescue medication or scheduled study medication) was 16.0 hour for those receiving Kadian every 24 hours; 9.1 hours for those on Kadian every 12 hours; and 8.7 hours for those on MS Contin every 12 hours, a significant difference between once-daily Kadian and twice-daily Kadian or MS Contin.

“Pain was controlled throughout the entire 24-hour dosing period in over 50% of patients on once-daily Kadian,” said Alan Broomhead, MBBS, of F.H. Faulding & Co. Ltd, Adelaide.

The patients’ global assessment of pain control significantly favored Kadian every 24 hours over MS Contin every 12 hours, with no difference between the two twice-daily groups (J Pain Symptom Manage 14:63-73, 1997). This better patient aceptance was achieved despite a bias against the once-daily regimen since placebo was given after 12 hours, the investigators said.

Efficacy in terms of the mean amount of rescue medication required and the percent of patients requiring rescue medication did not differ significantly among the groups, and morphine-related side effects were similar in all three groups.