Sublingual methadone for the management of cancer-related breakthrough pain: a pilot study.

Background: Breakthrough pain is a highly prevalent and difficult to manage cancer pain problem. Current strategies are frequently ineffective, in part because of a mismatch between the sudden onset and brief duration of breakthrough pain and the slower onset and more prolonged duration of oral immediate-release opioids. Novel analgesic interventions are needed to provide a closer match between the temporal profile of the pain and the pharmacodynamics of the pain medication, and novel models of study of breakthrough pain are needed to evaluate them.

Methods: This is an open-label feasibility study of a model to evaluate sublingual methadone for cancer-related breakthrough pain. The model has three phases: screening, upward titration, and optimal dose evaluation.

Results: Seven patients with breakthrough pain because of cancer entered the upward titration phase of the trial, and 61 episodes of breakthrough pain were evaluated with sublingual methadone at escalating doses ranging from 2-18 mg. Toxicity was generally mild and similar to patients' prior breakthrough medication. Four patients entered the optimal dose evaluation phase, and 39 discrete episodes of breakthrough pain were available for evaluation. Significant relief of pain occurred with a median onset of 5 minutes, and no serious adverse events were encountered.

Conclusions: This model of assessment of breakthrough pain, whereby each episode of pain is treated as a separate data set and multiple discrete episodes of breakthrough pain are assessed every 5 minutes in each patient, appears to be feasible within the cancer pain population. Preliminary results suggest a very rapid onset of relief of breakthrough pain with sublingual methadone when administered at the optimal dose, consistent with a highly favorable early pharmacodynamic profile of methadone administered via this route. Further study is warranted.