How Does Sublingual Fentanyl Measure Up Against Subcutaneous Morphine in Managing Cancer Pain?

Key Points

  • Use of sublingual fentanyl tablets was not noninferior to subcutaneous morphine in reducing pain during severe episodes in cancer patients receiving opioid treatment.
  • The average pain intensity over 30 minutes was 5.0 vs 4.5 on the 10-point scale.

An Italian single-center trial compared treatment with sublingual fentanyl tablets and subcutaneous morphine in managing severe pain episodes in cancer patients receiving opioid treatment. In the Journal of Clinical Oncology, Zecca et al reported that the trial did not show noninferiority of sublingual fentanyl vs subcutaneous morphine. There was a modest to moderate increased risk of lower efficacy with subcutaneous morphine, but patients preferred the sublingual route of administration.

Study Details

In the double-blind, double-dummy study, 114 patients enrolled at the outpatient palliative care clinic of the Fondazione IRCCS Istituto Nazionale dei Tumori–Milano between December 2013 and August 2015. They experienced a severe pain episode while receiving stable opioid therapy and were randomized to receive 100 mg of sublingual fentanyl tablets (n = 58) or 5 mg of subcutaneous morphine (n = 56).

Average pain intensity assessed on a 0 to 10 (highest pain) numerical rating scale at 10, 20, and 30 minutes postadministration was the primary endpoint. The main analysis was performed using an analysis of covariance adjusted by baseline pain intensity. Since the minimum clinically important difference on a 10-point pain scale is traditionally 2 points in assessing cancer pain, the noninferiority margin for the between-group difference was set at –0.6 (one-third of the minimum clinically important difference).

Reductions in Pain Intensity

Baseline mean pain intensity scores were 7.5 in both groups. Mean average scores over 10, 20, and 30 minutes postadministration were 5.0 in the sublingual fentanyl group vs 4.5 in the subcutaneous morphine group; since the 95% confidence interval (CI) of the between-group difference included the noninferiority margin (–0.49, 95% CI = –1.10 to 0.09), sublingual fentanyl did not meet noninferiority criteria. Average scores were 5.9 vs 5.4 at 10 minutes, 5.0 vs 4.4 at 20 minutes, and 3.9 vs 3.6 at 30 minutes. A second drug dose after 30 minutes was needed in 51% of the sublingual fentanyl group vs 37% of the subcutaneous morphine group (risk difference = –13%, 95% CI = –30% to 3%).

No serious adverse events were observed. Symptom mean intensity scores during follow-up were always lower than “A Little,” with the proportions of patients reporting scores of “Much” or “Very Much” at either 30 or 60 minutes never exceeding 13% in either group. No significant difference in the intensity of adverse events was found between the groups. The sublingual route of administration was preferred by 93% of patients, including 91% of the sublingual fentanyl group and 95% of the subcutaneous morphine group.

The investigators concluded: “This trial did not show noninferiority of [sublingual fentanyl tablets] versus [subcutaneous morphine] within the chosen [noninferiority margin]. Both treatments were safe, and patients preferred the sublingual route of administration. [Sublingual fentanyl tablets] provide analgesia with modest to moderate increased risk of lower efficacy compared with [subcutaneous morphine].”

The study was supported by the Italian Association for Cancer Research and the Floriani Foundation of Milan.

Cinzia Brunelli, PhD, of Fondazione IRCCS Istituto Nazionale dei Tumori-Milano, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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