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

Abstract

Topical morphine for treatment of cancer-related painful mucosal and cutaneous lesions: a double-blind, placebo-controlled cross-over clinical trial Aleksandra Ciałkowska-Rysz, Tomasz Dzierżanowski A b s t r a c t 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.

European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment

“…In case of local pain, a nerve block might diminish pain. In smaller wounds, application of morphine gel can be considered [125,126].…”

<p>Scalable in silico Simulation of Transdermal Drug Permeability: Application of BIOiSIM Platform</p>

“…We selected morphine because it has proven to be an effective analgesic agent and researchers are increasingly studying its topical applications to treat inflammation and pain in palliative care settings. 41,42 Morphine administration was modeled accurately by the base model across both the IV and transdermal route of administration, as measured by AAFE <3.0 for AUC0t and AAFE <1.5 for C max , t max across both experimental profiles. The higher optimized permeability value (0.16 cm/h) is expected given that the skin at the application site was de-epithelialized prior to compound administration.…”

“…44 More recently, Ciałkowska-Rysz et al found self-administered topical morphine to be a highly effective and safe medication for treating mucosal and skin lesions in palliative cancer patients, providing sustained pain relief for over 28 days. 41 The studies discussed above also suggest that the transdermal route is associated with a higher patient compliance as it offers evasive dosing, the possibility of self-administration, and flexibility in adjusting dosing regimen to experience rapid and long-lasting pain relief, hence the interest in accurate modeling and simulation.…”

A Practical Approach to Using Adjuvant Analgesics in Older Adults

“…One controlled trial found a strong trend supporting the efficacy of a gel containing baclofen 10 mg, amitriptyline 40 mg, and ketamine 20 mg for neuropathic symptoms associated with chemotherapy‐induced peripheral neuropathy and another small study favored menthol 1% in cancer‐related neuropathic pain . Topical morphine is used by some specialists in palliative care for pain associated with pressure ulcers or mucosal lesions …”