A phase III double-blind
equivalence study of two different formulations of slow-release morphine
followed by a randomization between dextromethorphan or placebo plus statex
SR for chronic cancer pain relief in terminally ill patients
While opioid agonists remain the main approach to managing advanced
cancer-related pain, approximately 40% achieve only partial relief with
current therapy. Activation of the NMDA receptor is thought to cause the
amplification & prolongation of the pain response & the development
of opioid tolerance. Dextromethorphan (DM) is an antitussive that exhibits
NMDA receptor antagonist properties. This multicentre, double blinded,
randomized phase III study had 2 phases. Objectives: Phase A examined
the efficacy & safety of Statex SR compared to MS-Contin. Phase B,
a placebo controlled trial, evaluated the efficacy & safety of DM as
a modulator of opioid tolerance in cancer patients with pain. Methods:
Phase A: Patients were randomized, after stratification for center &
total daily stabilization MS-Contin dose (<= 120mg or > 120mg) to Statex
SR or MS-Contin for 7 days. Phase B: Patients were again randomized to
Statex SR + DM or Statex SR + placebo for 14 days. During both phases patients
recorded medications & scores for pain, nausea, drowsiness & insomnia
twice daily. Results: Phase A: 87 patients randomized. The median
MS-Contin 24h dose was 90mg (range: 30-800). There was no statistically
significant difference in average pain, nausea, drowsiness, or insomnia
scores; percent increases in morphine consumption, number or timing of
first breakthrough dose. Phase B: 65 patients randomized. Although average
pain scores (12.6:15.8), number of breakthrough doses (9:11.3), & change
in total morphine consumption (550.9 mg:597.1 mg)was less in DM group than
placebo respectively, the difference was not statistically significant
(p=0.31-0.33). Nausea (5.4:5.4) & drowsiness (17:26.7)scores (DM:placebo)
were not statistically significant. Dizziness: 58% DM group VS 36% placebo.
Conclusions: Statex SR and MS-Contin have similar efficacy profiles.
DM, when added to morphine, results in a small, but not statistically significant,
modulation of opioid tolerance but causes more dizziness in cancer patients
with pain.
