Abstract
Dear Editor:
Currently, an effective treatment for malignant cutaneous wound pain has not been established. As many as 50,000 (10%) of the more than 500,000 people who die in the United States each year from cancer suffer from malignant wounds which produce a constellation of symptoms including pain. A small body of primarily anecdotal evidence suggests a large effect from topical opioid administration to control wound pain. Opioids bind to peripheral nerve receptors, particularly in an inflamed wound bed producing local analgesia. Of the five case reports reviewed, none reported local or systemic side effects from topical opioid application.1–3
We attempted to perform a randomized, double-blinded, placebo-controlled, crossover trial of topical morphine to reduce pain from malignant cutaneous wounds but only accrued five patients in 21 months. Of the patients enrolled only three were able to complete the seven-day protocol due to worsening of their condition. Acceptability by patients and their caregivers was quite high as is typical in therapeutic clinical trials. Five of six (83%) patients approached for inclusion consented. Patient #1 was a 61-year-old man with head and neck cancer with no response to medication or placebo. Patient #3 was a 66-year-old man with head and neck cancer and a positive response to morphine (numeric pain rating dropped from 4 to 1). Patient #5 was a 79-year-old-woman with lymphoma and a placebo effect. Thus we had equivocal findings.
Attempts to perform a randomized clinical trial were hampered by three factors. First, we used a single hospice agency, Hospice of Michigan (HOM), to recruit patients. Hospice of Michigan's southeast Michigan teams have an average daily census of about 300 patients. Though HOM is a large hospice agency, the proportion of patients enrolling into hospice with a primary diagnosis of cancer has decreased over time. A future multi-agency trial might ease this limitation. Second, part of the inclusion criteria required patients to have a palliative performance scale (PPS) score of at least 40%. The mean and median survival days for a patient with a PPS of 40% are 39.8 and 19, respectively. Enrolling patients with higher PPS is indicated, since two of the five enrolled patients were unable to complete the protocol due to a decline in their clinical condition. At a PPS of 50% the mean and median survival days are 53.5 and 34, respectively. 4 Third, with the first two factors considered, recruiting from a cancer center would access patients with potential malignant wounds earlier in their disease process and accordingly with higher PPS scores.
We established participant acceptability but were hampered by a very small sample with equivocal results; thus further study is needed. The anecdotal evidence at this time indicates a potential for significant pain reduction with topical opioids. If found to be effective in a properly powered sample, the implications for a new palliative intervention for the thousands of patients experiencing painful malignant could be significant.