Phase 1/2 Pilot Study of Methotrexate-Laurocapram Topical Gel for the Treatment of Patients With Early-Stage Mycosis Fungoides

Abstract

Objectives: To assess the safety and tolerability of a topical gel formulation combining methotrexate and laurocapram and to obtain preliminary information on the therapeutic potential of methotrexate-laurocapram in patients with early-stage mycosis fungoides (stage IA or IB).

Topical methotrexate in dermatology: a review of the literature

“…Of ten patients with early stage mycosis fungoides who were treated with topical MTXlaurocapram once every other day for 24 consecutive weeks, three attained greater than 50% improvement, four improved less than 50%, and zero had progressive disease. 24 Serum methotrexate concentration was below the lowest limit of detection, which ranged between 0.01-0.03 μmol/L, in all samples regardless of the dose received. 24 The patients in this study applied the gel formulation to the total body surface, excluding genital, perianal areas, nipples, face, and skin under the breasts, every other day for 24 consecutive weeks.…”

“…24 Serum methotrexate concentration was below the lowest limit of detection, which ranged between 0.01-0.03 μmol/L, in all samples regardless of the dose received. 24 The patients in this study applied the gel formulation to the total body surface, excluding genital, perianal areas, nipples, face, and skin under the breasts, every other day for 24 consecutive weeks.…”

New and Experimental Skin-Directed Therapies for Cutaneous Lymphomas

“…No systemic reactions or clinically significant laboratory abnormalities were observed. Serum levels of MTX, as measured 24-48 h following the topical application, were under the lowest limit of detection in all samples analysed [13] .…”

Topical treatments for early-stage mycosis fungoides using Grading Recommendations Assessment, Development and Evaluation (GRADE) criteria: A systematic review

“…Most were treated for 1.6-3.3 months with a maximum of 4 months Cutaneous adverse effects: erythema; telangiectasia; hyperpigmentation. Laboratory abnormalities: mild bone marrow depression; increase in aspartate aminotransferase Stage IA CR = 86%, Stage IB CR = 47%, Stage IIA CR = 55% with median time to achieve CR of 2.7 months Kannangara 2010 38 5-fluorouracil 6 patients; Stage IA = 4; stage IB = 1, Stage IIA = 1 5-fluorouracil applied daily to skin lesions for 3-18 months 2 patients experienced treatment-related adverse reactions that were mild and self-limited CR = 67% for 3-18 months Demierre 2003 39 Methotrexate-laurocapram 10 patients with stage IA or IB MF Doses of 12.5 or 25 g/m 2 applied to the entire skin surface every other day for 6 consecutive months A total of 10 adverse events were reported in 7/10 patients. Pruritus 60%; rash 20%; dry skin 10%; contact dermatitis 10% No CRs, slight-to-moderate response in 70% at 6 months Dummer 1993 40 Hexadecylphosphocholine 10 patients; Stage IA = 6; Stage IB = 2; Stage IIA = 2 Once daily application to a defined area during the first week, followed by twice daily application during the second week.…”

“…Several other studies on investigational therapies such as hexadecylphosphocholine, 40 peldesine, 41 ingenol mebutate, 42 resiquimod, 44 and combination therapies, such as methotrexate-laurocapram 39 and methotrexate-OFA-LP3, 43 were identified and included in the systematic review ( Table I ), but these therapies are not readily available for clinical use.…”