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JAMA Dermatology Jan 2013To evaluate the efficacy and safety of a novel mechlorethamine hydrochloride, 0.02%, gel in mycosis fungoides. DESIGN Randomized, controlled, observer-blinded,... (Comparative Study)
Comparative Study Randomized Controlled Trial
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.
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.
Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Female; Gels; Humans; Male; Mechlorethamine; Middle Aged; Mycosis Fungoides; Neoplasm Staging; Ointments; Severity of Illness Index; Single-Blind Method; Skin Neoplasms; Time Factors; Treatment Outcome; Young Adult
PubMed: 23069814
DOI: 10.1001/2013.jamadermatol.541 -
Journal of Chromatography. A Sep 2005Mechlorethamine in topical pharmaceutical formulations was derivatized with benzenethiol to form the disubstitution product and analyzed by normal-phase HPLC on silica...
Mechlorethamine in topical pharmaceutical formulations was derivatized with benzenethiol to form the disubstitution product and analyzed by normal-phase HPLC on silica gel using dibutyl phthalate as an internal standard. The derivatization reaction, purification, and isolation were conveniently performed in a single test tube. Analyses were successfully performed on three types of ointment formulations: anhydrous hydrophobic petrolatum-based ointments, anhydrous hydrophilic ointments, and hydrous hydrophilic ointments. Precision for the analysis of mechlorethamine standard or mechlorethamine in ointments ranged from 0.08 to 0.52% RSD (n = 6). Recoveries from ointments spiked with 0.02% mechlorethamine hydrochloride were 98.4-100.4%. The chromatograms were clean, showing minimal or no interference from ointment excipients or reagents.
Topics: Administration, Topical; Chromatography, High Pressure Liquid; Mechlorethamine; Molecular Structure; Pharmaceutical Preparations; Phenols; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet; Sulfhydryl Compounds
PubMed: 16106707
DOI: 10.1016/j.chroma.2005.06.057 -
International Journal of Dermatology Jun 1979The topical application of mechlorethamine is associated with a high incidence of irritant contact dermatitis. An attempt was made to avoid this complication by the use...
The topical application of mechlorethamine is associated with a high incidence of irritant contact dermatitis. An attempt was made to avoid this complication by the use of a topical tolerogenic schedule. Seven of ten patients developed contact dermatitis to the medication after they had completed the schedule, The use of this medication in its present form is unlikely to be practical value in the treatment of psoriasis.
Topics: Administration, Topical; Dermatitis, Contact; Drug Tolerance; Humans; Mechlorethamine; Psoriasis
PubMed: 468460
DOI: 10.1111/ijd.1979.18.5.390 -
Archives of Dermatology Aug 1976Eight patients with psoriasis who had developed contact allergy to mechlorethamine hydrochloride (nitrogen mustard) were subjected to a regimen of intravenous infusion...
Eight patients with psoriasis who had developed contact allergy to mechlorethamine hydrochloride (nitrogen mustard) were subjected to a regimen of intravenous infusion of small amounts of the drug in an attempt to produce desensitization. Although three of eight developed negative patch tests and were presumed to be desensitized, only one patient was able to use the drug therapeutically, and then only for a period of eight months, after which allergy recurred. The other two patients whose allergic contact dermatitis was abolished by the infusions were unable to use mechlorethamine therapeutically because of pruritus. Seven patients experienced some adverse reaction to the infusion. Intravenous desensitization of psoriatic patients who are allergic to mechlorethamine was not successful enough as a useful clinical procedure to allow them to once again use the drug therapeutically.
Topics: Administration, Topical; Dermatitis, Contact; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Male; Mechlorethamine; Psoriasis; Skin Tests
PubMed: 952529
DOI: No ID Found -
Clinical Lymphoma, Myeloma & Leukemia Jan 2024Chlormethine (CL) gel was approved for treatment of mycosis fungoides based on the pivotal 201 trial (NCT00168064). Data visualization from individual patients is a...
Evaluating Response Trends of Chlormethine/Mechlorethamine Gel in Patients With Stage I-IIA Mycosis Fungoides: Analysis of Individual Patient Data From a Randomized Controlled Phase II Study to Facilitate Optimal Treatment Experiences.
INTRODUCTION
Chlormethine (CL) gel was approved for treatment of mycosis fungoides based on the pivotal 201 trial (NCT00168064). Data visualization from individual patients is a powerful tool for discovery of hidden treatment trends. Here, we present a post hoc analysis of individual patient data from the pivotal trial to provide a more granular depiction of treatment and response changes over time, with an emphasis on end of treatment status.
MATERIALS AND METHODS
Individual patient response data were plotted over a 12-month treatment period to visualize patient experiences while using CL gel. Responder status was assigned according to end-of-treatment Composite Assessment of Index Lesion Severity (CAILS) score, and patients were classified as early (≤4 months) or late responders based on timing of response. Baseline and active treatment characteristics were compared between early and late responders, and baseline body surface area (BSA) was compared between responders and patients with stable or progressive disease.
RESULTS
Data from 123 patients with baseline and postbaseline results were included. At the end of treatment, 64.2%/55.3% were responders, 30.9%/34.1% had stable disease, and 4.9%/10.6% had progressive disease by CAILS and mSWAT, respectively. Among patients who responded to treatment, 64.6% and 35.4% were early and late responders, respectively. Response pattern analysis also identified patients with an intermittent response or initial progressive disease. Baseline BSA was not associated with responder status. Late responders had longer treatment duration and higher postbaseline plaque elevation, while early responders had a higher frequency of dermatitis.
CONCLUSIONS
Results presented here can facilitate optimal treatment experiences for patients starting CL gel.
Topics: Humans; Mechlorethamine; Mycosis Fungoides; Skin Neoplasms; Randomized Controlled Trials as Topic; Clinical Trials, Phase II as Topic
PubMed: 37802679
DOI: 10.1016/j.clml.2023.08.020 -
International Journal of Pharmaceutics Oct 2008Long term stability measurements were made for the nitrogen mustard mechlorethamine HCl at a concentration of 0.02% in six topical formulations: Aquaphor ointment,...
Long term stability measurements were made for the nitrogen mustard mechlorethamine HCl at a concentration of 0.02% in six topical formulations: Aquaphor ointment, Transcutol, Labrasol, 10% Transcutol in Aquaphor, 10% Transcutol in Labrasol, and Aquaphilic ointment. The drug decomposed gradually in Aquaphor ointment at room temperature, dropping to 95% in 4 weeks, 85% in 12 weeks, and 78% in 39 weeks. On the other hand, the drug decomposed rapidly in Aquaphilic ointment, giving an assay of less than 20% of its initial concentration after 24h at room temperature. Generally, mechlorethamine HCl was more stable in Aquaphor ointment than in formulations containing Transcutol or Labrasol. However, the addition of the free radical inhibitor, BHT, significantly enhanced the stability of mechlorethamine in Transcutol and Labrasol formulations. Four BHT-stabilized Transcutol and Labrasol formulations gave assays in ranges of 92-99% at the end of 4 weeks, 77-98% at the end of 12 weeks, and 38-93% at the end of 41 weeks.
Topics: Administration, Cutaneous; Antineoplastic Agents, Alkylating; Drug Compounding; Drug Delivery Systems; Drug Stability; Humans; Lymphoma, T-Cell, Cutaneous; Mechlorethamine; Ointments
PubMed: 18634862
DOI: 10.1016/j.ijpharm.2008.06.016 -
The American Journal of Medicine Mar 1948
Topics: Ethylamines; Mechlorethamine
PubMed: 18904050
DOI: 10.1016/0002-9343(48)90247-2 -
The Journal of Pharmacy and Pharmacology Dec 1950
Topics: Mechlorethamine; Nitrogen Mustard Compounds
PubMed: 14804313
DOI: 10.1111/j.2042-7158.1950.tb13010.x -
Archives of Dermatology Feb 1983A study was performed to determine the effect of UV-B radiation on the sensitization of patients to topically applied mechlorethamine hydrochloride. Patients with... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A study was performed to determine the effect of UV-B radiation on the sensitization of patients to topically applied mechlorethamine hydrochloride. Patients with widespread psoriasis were randomized into two groups. One group was given six daily treatments of one minimal erythemal dose (MErD) prior to starting daily applications of a 0.02% mechlorethamine ointment and, thereafter, one MErD weekly; the other group was given daily applications of mechlorethamine but received no UV-B. The improvement of psoriasis was monitored by a severity score system and patients were treated for 30 days, or until contact dermatitis occurred. The addition of UV-B to topical applications of mechlorethamine reduced the incidence of allergic contact dermatitis to mechlorethamine from 64% to 22%. In those sensitized to mechlorethamine, the time required for sensitization to develop was increased from 14 to 23 days by UV-B therapy.
Topics: Administration, Topical; Aged; Clinical Trials as Topic; Dermatitis, Contact; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Delayed; Male; Mechlorethamine; Middle Aged; Psoriasis; Random Allocation; Time Factors; Ultraviolet Therapy
PubMed: 6337558
DOI: 10.1001/archderm.119.2.117 -
Journal of Medicinal Chemistry Mar 1990Many cancer cells are resistant to chemotherapeutic treatment with mechlorethamine and other alkylating agents. These drug-resistant cells often show an increase in the...
Many cancer cells are resistant to chemotherapeutic treatment with mechlorethamine and other alkylating agents. These drug-resistant cells often show an increase in the intracellular concentration of glutathione and an increase in the activity of glutathione-S-transferase when compared to the sensitive cells. Both of these components are thought to be involved with inactivation of the drug either through conjugation with glutathione or by hydrolysis. NMR spectroscopy was used to monitor the nonenzymatic conjugation of mechlorethamine with glutathione. Several intermediates along the pathway to the doubly glutathione substituted mustard, including both mustard-aziridinium adducts, can be observed. The assignment of the 1H NMR spectrum of these adducts are presented. At 30 degrees C, pH 7.0, no hydrolyzed mustard was detectable. With the use of 13C-labeled mustard, the conjugation reaction can be shown to proceed through an aziridinium intermediate rather than by direct nucleophilic substitution.
Topics: Glutathione; Magnetic Resonance Spectroscopy; Mechlorethamine
PubMed: 2308133
DOI: 10.1021/jm00165a019