MONTREAL-In a small Canadian study of patients with cancer-related
pain, nearly 75% said that 12-hour dosing with sustained-release
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
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.