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

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

Research output: Contribution to journalArticle

44 Citations (Scopus)

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 drugrelated 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.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalJAMA Dermatology
Volume149
Issue number1
DOIs
StatePublished - Jan 2013

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Cutaneous T-Cell Lymphoma
Mechlorethamine
Mycosis Fungoides
Multicenter Studies
Randomized Controlled Trials
Gels
Safety
Ointments
Drug Therapy
Carmustine
Therapeutics
Pharmaceutical Preparations
Neoplasms
Outcome Assessment (Health Care)
Skin

ASJC Scopus subject areas

  • Dermatology

Cite this

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. / Lessin, Stuart R.; Duvic, Madeleine; Guitart, Joan; Pandya, Amit G.; Strober, Bruce E.; Olsen, Elise A.; Hull, Christopher M.; Knobler, Elizabeth H.; Rook, Alain H.; Kim, Ellen J.; Naylor, Mark F.; Adelson, David M.; Kimball, Alexa B.; Wood, Gary S.; Sundram, Uma; Wu, Hong; Kim, Youn H.

In: JAMA Dermatology, Vol. 149, No. 1, 01.2013, p. 25-32.

Research output: Contribution to journalArticle

Lessin, SR, Duvic, M, Guitart, J, Pandya, AG, Strober, BE, Olsen, EA, Hull, CM, Knobler, EH, Rook, AH, Kim, EJ, Naylor, MF, Adelson, DM, Kimball, AB, Wood, GS, Sundram, U, Wu, H & Kim, YH 2013, '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', JAMA Dermatology, vol. 149, no. 1, pp. 25-32. https://doi.org/10.1001/2013.jamadermatol.541
Lessin, Stuart R. ; Duvic, Madeleine ; Guitart, Joan ; Pandya, Amit G. ; Strober, Bruce E. ; Olsen, Elise A. ; Hull, Christopher M. ; Knobler, Elizabeth H. ; Rook, Alain H. ; Kim, Ellen J. ; Naylor, Mark F. ; Adelson, David M. ; Kimball, Alexa B. ; Wood, Gary S. ; Sundram, Uma ; Wu, Hong ; Kim, Youn H. / 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. In: JAMA Dermatology. 2013 ; Vol. 149, No. 1. pp. 25-32.
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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 drugrelated 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.",
author = "Lessin, {Stuart R.} and Madeleine Duvic and Joan Guitart and Pandya, {Amit G.} and Strober, {Bruce E.} and Olsen, {Elise A.} and Hull, {Christopher M.} and Knobler, {Elizabeth H.} and Rook, {Alain H.} and Kim, {Ellen J.} and Naylor, {Mark F.} and Adelson, {David M.} and Kimball, {Alexa B.} and Wood, {Gary S.} and Uma Sundram and Hong Wu and Kim, {Youn H.}",
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T2 - Positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides

AU - Lessin, Stuart R.

AU - Duvic, Madeleine

AU - Guitart, Joan

AU - Pandya, Amit G.

AU - Strober, Bruce E.

AU - Olsen, Elise A.

AU - Hull, Christopher M.

AU - Knobler, Elizabeth H.

AU - Rook, Alain H.

AU - Kim, Ellen J.

AU - Naylor, Mark F.

AU - Adelson, David M.

AU - Kimball, Alexa B.

AU - Wood, Gary S.

AU - Sundram, Uma

AU - Wu, Hong

AU - Kim, Youn H.

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N2 - 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 drugrelated 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.

AB - 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 drugrelated 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.

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