THE DOSE-RESPONSE RELATIONSHIP OF CONTROLLED-RELEASE CODEINE (CODEINE-CONTIN) IN CHRONIC CANCER PAIN

The improved pain control provided by regular dosing of opioid analgesics in patients with severe cancer pain has been well established. However, the treatment of mild-to-moderate cancer pain is often limited to ''as needed'' dosing with fixed combinations of codeine or oxycodone plus a nonopioid analgesic, which do not allow optimal titration of the individual components. This randomized double-blind study was designed to evaluate the efficacy of controlled-release codeine (Codeine Contin) in patients with cancer pain, and to estimate its dose equivalence to a standard combination of acetaminophen plus codeine. Twenty-four patients with at least moderate cancer pain were randomized to Codeine Contin 100, 200, or 300 mg every 12 hr or acetaminophen plus codeine (600 mg/60 mg) every 6 hr. On days 1 and 4 of dosing, pain intensity and pain relief were assessed hourly for 12 hr. The sum of pain intensity differences (SPID) from baseline and the total pain relief (TOTPAR) scores demonstrated a dose-response relationship for Codeine Contin on days 1 and 4 that was statistically significant on day 1 and suggested greater analgesic efficacy on day 4, compared with day 1. Codeine Contin 150 mg every 12 hr was estimated to be equianalgesic to acetaminophen plus codeine (600 mg/60 mg) given every 6 hr. Because a similar equivalence was also demonstrated from analysis of adverse arent data, it is concluded that Codeine Contin 150 mg produces analgesia and a side-effect profile similar to a 40% lower dose of codeine provided by the combination. These results indicate the need for studies of scheduled every-l2-hr dosing of Codeine Contin in comparison to ''as needed'' dosing of combination preparations in patients with cancer pain.