MONTREAL-In a small Canadian study of patients with cancer-related pain, nearly 75% said that 12-hour dosing with sustained-release morphine(Drug information on morphine) sulfate tablets (MS Contin) offers advantages over 8-hour dosing, and nearly all (94.5%) preferred 12-hour to 4-hour dosing, report Gérard G. Mignault, MD, and colleagues from the Hôtel-Dieu de Mon-tréal and Purdue Frederick, Pickering, Ontario, manufacturer of MS Contin.
This double-blind, randomized, crossover trial enrolled 27 patients with a diagnosis of cancer-related pain of moderate or severe intensity who were already stabilized on oral opioids. The 19 eval-uable patients were crossed over from 12-hour dosing to 8-hour dosing (or vice versa) after 5 days of administration. Blindness was maintained by giving placebo tablets so that each patient took medication four times a day. Supplemental oral morphine solution was available for episodes of breakthrough pain.
Pain intensity and pain relief were measured four times each day using a 10-cm visual analog scale; occurrence and severity of common opioid side effects were measured on a scale of 0 (none) to 3 (severe).
The results showed no advantage for 8-hour dosing in terms of pain intensity, pain relief, adverse event severity, and use of rescue morphine (J Pain Symptom Manage 10:416-422, 1995). The researchers pointed out that a small number of differences were detected (for pain relief and individual adverse events) on specific days, but these were not consistent at any given assessment time or overall.
The investigators note that their trial confirms results from other studies indicating that less than 10% of patients are likely to require MS Contin more frequently than every 12 hours. They recommend that the 8-hour dosing schedule be used only if the patient has reproducibly shown breakthrough pain at the end of the 12-hour dosing interval, despite appropriate dose titration, or if side effects reproducibly occur within the first few hours of a 12-hour schedule.
Dr. Mignault's colleagues in the study were Jean Latreille, MD, Francis Viguié, PhD, Pierre Richer, MD, and Francois Lemire, BSc (Pharm), from the Hôtel-Dieu de Montreal, and Zoltan Harsanyi, MBA, and John H. Stewart, MSc, from Purdue Frederick.