Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides.

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of a novel mechlorethamine hydrochloride, 0.02%, gel in mycosis fungoides. DESIGN Randomized, controlled, observer-blinded, multicenter trial comparing mechlorethamine, 0.02%, gel with mechlorethamine, 0.02%, compounded ointment. Mechlorethamine was applied once daily for up to 12 months. Tumor response and adverse events were assessed every month between months 1 and 6 and every 2 months between months 7 and 12. Serum drug levels were evaluated in a subset of patients.

SETTING:

Academic medical or cancer centers.

PATIENTS:

In total, 260 patients with stage IA to IIA mycosis fungoides who had not used topical mechlorethamine within 2 years and were naive to prior use of topical carmustine therapy.

MAIN OUTCOME MEASURES:

Response rates of all the patients based on a primary clinical end point (Composite Assessment of Index Lesion Severity) and secondary clinical end points (Modified Severity-Weighted Assessment Tool and time-to-response analyses).

RESULTS:

Response rates for mechlorethamine gel vs ointment were 58.5% vs 47.7% by the Composite Assessment of Index Lesion Severity and 46.9% vs 46.2% by the Modified Severity-Weighted Assessment Tool. By 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). No drug-related serious adverse events were seen. Approximately 20.3% of enrolled patients in the gel treatment arm and 17.3% of enrolled patients in the ointment treatment arm withdrew because of drug-related skin irritation. No systemic absorption of the study medication was detected.

CONCLUSION:

The use of a novel mechlorethamine, 0.02%, gel in the treatment of patients with mycosis fungoides is effective and safe.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier:NCT00168064.

• Authors: Stuart R Lessin, Madeleine Duvic, Joan Guitart, Amit G Pandya, Bruce E Strober, Elise A Olsen, Christopher M Hull, Elizabeth H Knobler, Alain H Rook, Ellen J Kim, Mark F Naylor, David M Adelson, Alexa B Kimball, Gary S Wood, Uma Sundram, Hong Wu, Youn H Kim
• Journal: JAMA dermatology (JAMA Dermatol) Vol. 149 Issue 1 Pg. 25-32 (Jan 2013) ISSN: 2168-6084 [Electronic] United States
• PMID: 23069814 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents, Alkylating
• Gels
• Ointments
• Mechlorethamine

Topics

• Administration, Cutaneous
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Alkylating (administration & dosage, adverse effects, therapeutic use)
• Female
• Gels
• Humans
• Male
• Mechlorethamine (administration & dosage, adverse effects, therapeutic use)
• Middle Aged
• Mycosis Fungoides (drug therapy, pathology)
• Neoplasm Staging
• Ointments
• Severity of Illness Index
• Single-Blind Method
• Skin Neoplasms (drug therapy, pathology)
• Time Factors
• Treatment Outcome
• Young Adult