Topical morphine for treatment of cancer-related painful mucosal and cutaneous lesions: a double-blind, placebo-controlled cross-over clinical trial

Introduction: Painful mucosal and cutaneous lesions are often less responsive or even refractory to systemic opioid analgesics. There is evidence suggesting that the effectiveness of topical morphine be restricted to inflammatory pain. The studied groups were small and the observation period relatively short. The aim of this study was to assess the effectiveness and safety of topical morphine for pain related to mucosal lesions and skin ulcers. Material and methods: The study was a 14-day randomized placebo-controlled cross-over trial (RCT) with a 28-day follow-up open phase (OP). The trial was conducted in adult patients with localized cancer-related pain and treated with systemic opioids in an oncology center or home hospice. The patients administered 0.2% gel on the mucosal lesion or 0.2% ointment on the skin lesion by themselves, without restrictions regarding the number of doses per day. The primary measurements were mean pain intensity (MPI) and mean pain relief (MPR) on the numeric rating scale (NRS 0-10), and ITT analysis was performed. Results: Thirty-five patients were randomized to the RCT, and all of them completed 14-day observation. The MPI before the treatment was NRS 5.9 and decreased to 2.5 after morphine (p < 0.0001 vs. placebo). The MPR was 57% after morphine, and 77% of the patients using topical morphine obtained clinically significant (at least 50% of the starting value) pain relief, statistically different from placebo. The analgesic effect was sustained over the 28-day OP period (p = 0.00001). There were only 2 cases of moderate pruritus, and no other side effects were reported. Conclusions: Topical morphine was found to be a fast acting, highly effective, and safe medication for mucosal and skin lesions in palliative patients, with a sustainable pain relief effect over the 28-day observation period.