A novel mechlorethamine, 0.02%, gel produced comparable or higher response rates (depending on the measurement used) than did mechlorethamine, 0.02%, compounded ointment, in a randomized controlled, multicenter study among 260 patients with stage IA to IIA mycosis fungoides, the most common form of cutaneous T-cell lymphoma. The patients had not used topical mechlorethamine within 2 years and were naive to prior use of topical carmustine (BiCNU) therapy. The mechlorethamine was applied once daily to either specific lesions or to the total skin surface, depending on the T classification, for up to 12 months.
Based on the Composite Assessment of Index Lesion Severity, the primary efficacy endpoint, which identified up to five index lesions as baseline and assessed them throughout the study, response rates were 58.5% for the gel vs 47.7% for the ointment. Using the Composite Assessment of Index Lesion Severity, the ratio of gel response rate to ointment response rate was 1.23 (95% CI = 0.97–1.55), “which met the prespecified criterion for noninferiority. Time-to-response analyses demonstrated superiority of mechlorethamine gel to ointment (P < .01),” the investigators reported in the Archives of Dermatology.
Because regional and total skin surface applications were also included in the study, the investigators used the Modified Severity-Weighted Assessment Tool as a secondary efficacy endpoint. “A determination of the percentage involvement of total body surface area and, if applicable, an assessment of clinically abnormal lymph nodes (> 1.5 cm in diameter) were completed at baseline and throughout the 12-month study,” the authors explained. By this measure, response rates were 46.9% for the gel vs 46.2% for the ointment.
While no drug-related severe adverse events were reported during the trial, “61.7% of patients who received gel and 50.4% of patients who received ointment reported at least 1 [adverse event] that was considered related to the study drug,” the researchers noted. “Most [adverse events] in both treatment arms were skin related, characterized mainly as local dermatitis (skin irritation). The incidence of skin irritation was higher in the gel arm (P = .04). No statistically significant differences were observed in the overall incidence of [adverse events] or any other subcategory between the gel and ointment arms.” Drug-related skin adverse events were responsible for withdrawal from the trial by 20.3% of patients using gel and 17.3% using ointment.
In an assertion that takes on added significance with recent reports of people dying from meningitis caused by a contaminated drug from a compounding pharmacy, the authors noted that the lack of a topical mechlorethamine formulation approved by the FDA “has become problematic for physicians and patients for several reasons.” Among the reasons cited is: “Pharmacy-compounded mechlorethamine formulations are not subject to rigorous quality assurance, such as evaluations of potency and stability.” The authors concluded, “A manufactured mechlorethamine, 0.02%, gel [would address] the unmet need for good manufacturing product quality assurance that will improve drug availability for patients with [mycosis fungoides].” ■
Lessin SR, et al: Arch Dermatol October 15, 2012 (online first).