Literature DB >> 23069814

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 Lessin1, 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.   

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.

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Year:  2013        PMID: 23069814      PMCID: PMC3662469          DOI: 10.1001/2013.jamadermatol.541

Source DB:  PubMed          Journal:  JAMA Dermatol        ISSN: 2168-6068            Impact factor:   10.282


  23 in total

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Journal:  Dermatologica       Date:  1965

2.  Nitrogen mustard therapy; use of methyl-bis (beta-chloroethyl) amine hydrochloride and tris (beta-chloroethyl) amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders.

Authors:  L S GOODMAN; M M WINTROBE
Journal:  J Am Med Assoc       Date:  1946-09-21

3.  Long-term efficacy, curative potential, and carcinogenicity of topical mechlorethamine chemotherapy in cutaneous T cell lymphoma.

Authors:  E C Vonderheid; E T Tan; A F Kantor; L Shrager; B Micaily; E J Van Scott
Journal:  J Am Acad Dermatol       Date:  1989-03       Impact factor: 11.527

4.  Clinical end points and response criteria in mycosis fungoides and Sézary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer.

Authors:  Elise A Olsen; Sean Whittaker; Youn H Kim; Madeleine Duvic; H Miles Prince; Stuart R Lessin; Gary S Wood; Rein Willemze; Marie-France Demierre; Nicola Pimpinelli; Maria Grazia Bernengo; Pablo L Ortiz-Romero; Martine Bagot; Teresa Estrach; Joan Guitart; Robert Knobler; José Antonio Sanches; Keiji Iwatsuki; Makoto Sugaya; Reinhard Dummer; Mark Pittelkow; Richard Hoppe; Sareeta Parker; Larisa Geskin; Lauren Pinter-Brown; Michael Girardi; Günter Burg; Annamari Ranki; Maartan Vermeer; Steven Horwitz; Peter Heald; Steve Rosen; Lorenzo Cerroni; Brigette Dreno; Eric C Vonderheid
Journal:  J Clin Oncol       Date:  2011-05-16       Impact factor: 44.544

5.  Topical nitrogen mustard in the management of mycosis fungoides: update of the Stanford experience.

Authors:  Youn H Kim; Gina Martinez; Anna Varghese; Richard T Hoppe
Journal:  Arch Dermatol       Date:  2003-02

Review 6.  Defining early mycosis fungoides.

Authors:  Nicola Pimpinelli; Elise A Olsen; Marco Santucci; Eric Vonderheid; Andreas C Haeffner; Seth Stevens; Guenter Burg; Lorenzo Cerroni; Brigitte Dreno; Earl Glusac; Joan Guitart; Peter W Heald; Werner Kempf; Robert Knobler; Stuart Lessin; Christian Sander; Bruce S Smoller; Gladys Telang; Sean Whittaker; Keiji Iwatsuki; Erik Obitz; Masahiro Takigawa; Maria L Turner; Gary S Wood
Journal:  J Am Acad Dermatol       Date:  2005-12       Impact factor: 11.527

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Journal:  Arch Dermatol       Date:  1996-11

8.  Topical mechlorethamine therapy for early stage mycosis fungoides.

Authors:  D L Ramsay; P S Halperin; A Zeleniuch-Jacquotte
Journal:  J Am Acad Dermatol       Date:  1988-10       Impact factor: 11.527

Review 9.  Topical treatment of early cutaneous T-cell lymphoma.

Authors:  D L Ramsay; J A Meller; H S Zackheim
Journal:  Hematol Oncol Clin North Am       Date:  1995-10       Impact factor: 3.722

10.  Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression.

Authors:  Youn H Kim; Howard L Liu; Serena Mraz-Gernhard; Anna Varghese; Richard T Hoppe
Journal:  Arch Dermatol       Date:  2003-07
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  32 in total

1.  Evaluation of O6-Benzylguanine-Potentiated Topical Carmustine for Mycosis Fungoides: A Phase 1-2 Clinical Trial.

Authors:  Joselin D Tacastacas; Derek V Chan; Sean Carlson; Stanton L Gerson; Afshin Dowlati; Pingfu Fu; Kurt Lu; Sarah Groft; Julie Rosenjack; Kord Honda; Thomas S McCormick; Kevin D Cooper
Journal:  JAMA Dermatol       Date:  2017-05-01       Impact factor: 10.282

2.  Interventions for mycosis fungoides.

Authors:  Arash Valipour; Manuel Jäger; Peggy Wu; Jochen Schmitt; Charles Bunch; Tobias Weberschock
Journal:  Cochrane Database Syst Rev       Date:  2020-07-07

Review 3.  Cutaneous T cell lymphoma.

Authors:  Reinhard Dummer; Maarten H Vermeer; Julia J Scarisbrick; Youn H Kim; Connor Stonesifer; Cornelis P Tensen; Larisa J Geskin; Pietro Quaglino; Egle Ramelyte
Journal:  Nat Rev Dis Primers       Date:  2021-08-26       Impact factor: 52.329

4.  How we treat mycosis fungoides and Sézary syndrome.

Authors:  Niloufer Khan; Sarah J Noor; Steven Horwitz
Journal:  Clin Adv Hematol Oncol       Date:  2021-09

5.  Management of Mycosis Fungoides with Topical Chlormethine/Mechlorethamine Gel: A Columbia University Cutaneous Lymphoma Center Experience.

Authors:  Tiffany J Garcia-Saleem; Connor J Stonesifer; Alexandra E Khaleel; Larisa J Geskin
Journal:  Acta Derm Venereol       Date:  2021-09-08       Impact factor: 3.875

Review 6.  Mycosis Fungoides and Sézary Syndrome: Updates and Review of Current Therapy.

Authors:  Hiroaki Kamijo; Tomomitsu Miyagaki
Journal:  Curr Treat Options Oncol       Date:  2021-01-07

7.  Jak-STAT Inhibition Mediates Romidepsin and Mechlorethamine Synergism in Cutaneous T-Cell Lymphoma.

Authors:  Jose R Cortes; Christina C Patrone; Stuart Aidan Quinn; Yuhan Gu; Marta Sanchez-Martin; Adam Mackey; Anisha J Cooke; Bobby B Shih; Anouchka P Laurent; Megan H Trager; Adolfo A Ferrando; Larisa J Geskin; Teresa Palomero
Journal:  J Invest Dermatol       Date:  2021-06-03       Impact factor: 7.590

8.  Post hoc Analysis of a Randomized, Controlled, Phase 2 Study to Assess Response Rates with Chlormethine/Mechlorethamine Gel in Patients with Stage IA-IIA Mycosis Fungoides.

Authors:  Christiane Querfeld; Julia J Scarisbrick; Chalid Assaf; Emmanuella Guenova; Martine Bagot; Pablo Luis Ortiz-Romero; Pietro Quaglino; Erminio Bonizzoni; Emmilia Hodak
Journal:  Dermatology       Date:  2021-06-04       Impact factor: 5.366

9.  A Little Experience Goes a Long Way: Chlormethine/Mechlorethamine Treatment Duration as a Function of Clinician-Level Patient Volume for Mycosis Fungoides Cutaneous T-Cell Lymphoma (MF-CTCL)-A Retrospective Cohort Study.

Authors:  Christiane Querfeld; Theresa Pacheco; Bradley Haverkos; Gary Binder; James Angello; Brian Poligone
Journal:  Front Med (Lausanne)       Date:  2021-07-02

10.  Cutaneous T-cell lymphomas: 2021 update on diagnosis, risk-stratification, and management.

Authors:  Alexandra C Hristov; Trilokraj Tejasvi; Ryan A Wilcox
Journal:  Am J Hematol       Date:  2021-08-02       Impact factor: 13.265

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