Mechlorethamine hydrochloride, a nitrogen mustard-derivative alkylating agent, is an antineoplastic agent.1, 3, 4
Mycosis Fungoides-type Cutaneous T-cell Lymphoma
Mechlorethamine hydrochloride gel is used for the topical treatment of cutaneous lesions in patients with early (stage IA and IB) mycosis fungoides-type cutaneous T-cell lymphoma (CTCL) who have received prior skin-directed therapy.1 Mechlorethamine has been designated an orphan drug by the US Food and Drug Administration (FDA) for use in this condition.2
Efficacy of mechlorethamine gel was evaluated in a randomized, multicenter, observer-blinded, active-controlled clinical trial in 260 patients with stage IA, IB, or IIA mycosis fungoides-type CTCL who had received at least one prior skin-directed therapy (e.g., topical corticosteroids, phototherapy, bexarotene gel, other topical mechlorethamine preparations); patients were not required to have been refractory to or intolerant of prior therapy.1, 3, 7 Patients who had received topical mechlorethamine within the previous 2 years, radiation therapy within 1 year, or prior treatment with carmustine were excluded.3 Patients in the mechlorethamine gel and comparator (mechlorethamine ointment) groups were similar with respect to age (median: 58 years), gender (59% male), race (75% white), number of prior therapies (median: 2; range: 1-12), prior topical corticosteroid use (86%), and body surface area involvement at baseline (median: 8.5-9%; range: 1-76%).1, 3 Patients were stratified by stage of disease and randomized to receive mechlorethamine 0.016% (0.02% mechlorethamine hydrochloride) gel or a comparator consisting of a hydrophilic petrolatum-based mechlorethamine hydrochloride 0.02% ointment, to be applied once daily (to specific lesions or total skin surface, depending on extent and type of skin involvement) for 12 months; interruption of therapy and/or reduction in frequency of administration were allowed in patients experiencing dermatitis.1, 3 Patients were not allowed to receive concomitant therapy with topical or systemic corticosteroids.1, 3 The mean amount of mechlorethamine gel used during the study was 2.8 g per day, with maximum daily usage of 10.5 g.1
The primary measure of efficacy was the proportion of patients who achieved a response in Composite Assessment of Index Lesion Severity (CAILS) score, defined as a reduction of at least 50% from baseline that was confirmed at least 4 weeks later; a complete response was defined as a confirmed CAILS score of zero.1, 3 The CAILS score provides an assessment of local or target lesion response and is obtained by adding the severity scores in the following categories for up to 5 index lesions: erythema, scaling, plaque elevation, and surface area.1, 10 A CAILS score response was achieved in 60% of patients receiving mechlorethamine gel and 48% of patients receiving mechlorethamine ointment; the gel was noninferior to the ointment, with an overall CAILS response ratio of 1.24 (95% confidence interval: 0.98-1.58).1, 7 A complete CAILS score response was achieved in 14 or 11% of patients receiving mechlorethamine gel or ointment, respectively; onset of overall response ranged from 1-11 months.1
A secondary measure of efficacy was the proportion of patients who achieved a response in Severity Weighted Assessment Tool (SWAT) score, defined as a reduction of at least 50% from baseline that was confirmed at least 4 weeks later.1, 3 The SWAT score provides a global assessment of extent and severity of skin involvement and is derived by measuring the involved area in each body region as a percentage of body surface area and multiplying the sum of the body surface areas for each lesion type by a severity weighting factor (1 for patch, 2 for plaque, and 3 for tumor or ulcer).1, 10 Overall and complete SWAT score responses were achieved in 50 and 7%, respectively, of patients receiving mechlorethamine gel and 46 and 3%, respectively, of those receiving the ointment.1
Mechlorethamine also has been used topically for the treatment of mycosis fungoides-type CTCL as an aqueous solution or ointment-based preparation compounded using mechlorethamine hydrochloride for injection.3, 4, 7, 8, 11, 21, 22 Expert treatment guidelines include topical mechlorethamine as one of several recommended treatment options for patients with early stages of this disease.5, 6, 8, 9
Mechlorethamine hydrochloride is applied topically to the skin as a gel containing 0.016% mechlorethamine.1 The commercially available mechlorethamine hydrochloride gel is for topical dermatologic use only .1
Mechlorethamine also has been applied topically to the skin as a solution or ointment-based preparation compounded extemporaneously using mechlorethamine hydrochloride for injection.3, 4, 7, 8, 11 Solutions usually are prepared by dissolving 10 mg of mechlorethamine hydrochloride in 50-100 mL of water.4, 11, 16, 17, 18, 19, 20 Because of limited stability, solutions of the drug must be prepared immediately before use.4, 11 Ointments containing mechlorethamine hydrochloride (typically in a concentration of 0.01 or 0.02%3, 4, 7, 8, 11, 12, 14, 15 ) usually are prepared by dissolving the drug in dehydrated alcohol, filtering the solution to remove the insoluble sodium chloride that is present in the commercial preparation (although filtration may not be necessary), and mixing the drug-alcohol solution into petrolatum or another anhydrous ointment base (e.g., hydrophilic petrolatum).11, 12, 15 Clinicians should consult specialized references for detailed information on the preparation of topical mechlorethamine solutions and ointments.
Mechlorethamine should not be applied near or in the eyes, nose, or mouth.1 (See Mucosal or Eye Injury under Cautions: Warnings/Precautions.) Patients should be directed to wash their hands thoroughly with soap and water after handling or applying the drug. 1
Mechlorethamine gel must be stored in the freezer at -25 to -15°C prior to dispensing and in the original box in the refrigerator at 2-8°C after dispensing; any unused gel should be discarded 60 days after dispensing.1
Mechlorethamine hydrochloride gel should be applied immediately (or within 30 minutes) after removal from the refrigerator; the gel should be returned to the refrigerator immediately after each use.1 The gel should be applied to completely dry skin at least 4 hours before or at least 30 minutes after showering or washing the affected areas.1 After application of the gel, the treated areas should be allowed to dry for 5-10 minutes before covering with clothing.1 Emollients (moisturizers) may be applied to the treated areas 2 hours before or 2 hours after application of the gel.1 Occlusive dressings should not be used on treated areas.1 Mechlorethamine gel is flammable; therefore, fire, flame, and smoking should be avoided until the gel has dried.1
The manufacturer states that if a caregiver applies mechlorethamine hydrochloride gel to a patient, the caregiver must wear disposable nitrile gloves during application and must wash their hands thoroughly with soap and water after removing the gloves.1 In case of accidental skin exposure to mechlorethamine gel, a caregiver must immediately wash exposed areas thoroughly with soap and water for at least 15 minutes and remove contaminated clothing.1 If secondary exposure to the eyes, mouth, or nose occurs, the exposed area should be irrigated immediately for at least 15 minutes with copious amounts of water.1
Dosage of mechlorethamine hydrochloride gel is expressed in terms of mechlorethamine.1
For the topical treatment of cutaneous lesions in patients with early (stage IA and IB) mycosis fungoides-type cutaneous T-cell lymphoma (CTCL), a thin film of mechlorethamine 0.016% gel should be applied to affected areas of the skin once daily.1 If any skin ulceration or blistering or moderately severe or severe dermatitis (i.e., marked erythema with edema) occurs, treatment with mechlorethamine gel should be interrupted.1 Upon improvement, treatment may be resumed with a reduced frequency of once every 3 days.1 If reintroduction of treatment is tolerated for at least one week, the application frequency may be increased to every other day for at least one week and then to once daily if tolerated.1
When extemporaneously prepared topical solutions and ointments have been used for the treatment of cutaneous lesions of mycosis fungoides-type CTCL, the concentration of mechlorethamine hydrochloride, frequency of application, and duration of treatment have been based on the dermatologic response and tolerance of the patient.4, 11, 16 The usual concentration of mechlorethamine hydrochloride used in ointment preparations is 0.01 or 0.02%;3, 4, 7, 8, 11, 12, 14, 15 lower concentrations may be used initially in patients with dermatitis or a history of hypersensitivity reactions to the topically applied drug, and higher concentrations may be used in patients with extensive or resistant lesions.4, 11, 12, 14, 15
Applications of mechlorethamine generally are repeated once daily until the lesions disappear.4, 11 The optimal duration of topical mechlorethamine therapy following clinical remission has not been fully established.4, 8, 11
Mechlorethamine gel is contraindicated in patients with known severe hypersensitivity to the drug.1
Hypersensitivity reactions, including anaphylaxis, have occurred following exposure to topical formulations of mechlorethamine.1, 4, 11, 21 In patients who develop a hypersensitivity reaction, desensitization using topical mechlorethamine has been used with some success to prevent allergic contact dermatitis with additional therapy.4, 11, 12 One patient sensitized to topical mechlorethamine reportedly experienced pruritus and diffuse angioedema with IV cyclophosphamide.13
Exposure of the eyes to mechlorethamine causes pain, burns, inflammation, photophobia, and blurred vision and can lead to blindness and severe irreversible anterior eye injury.1 If eye exposure occurs, the affected eye(s) must be irrigated immediately with copious amounts of water, 0.9% sodium chloride, or a balanced salt ophthalmic irrigating solution for at least 15 minutes and immediate medical care, including ophthalmologic consultation, should be obtained.1
Exposure of mucous membranes (e.g., oral or nasal mucosa) to mechlorethamine causes pain, erythema, and ulceration, which may be severe.1 If mucosal exposure occurs, the affected area should be irrigated immediately with copious amounts of water for at least 15 minutes and immediate medical consultation should be obtained.1
Secondary Exposure to Topical Mechlorethamine
Direct skin contact with mechlorethamine should be avoided by anyone other than the patient.1 Risks associated with such secondary exposure include dermatitis, mucosal injury, and secondary cancers.1 Application instructions should be followed carefully to prevent secondary exposure (see Dosage and Administration: Administration).1
Dermatitis is the most common adverse effect of topically administered mechlorethamine.1, 3, 4, 11 Following application of mechlorethamine hydrochloride gel, dermatitis occurred in 56% of patients and was moderately severe or severe in 23% of patients.1 Patients should be monitored for erythema, swelling, inflammation, pruritus, blisters, ulceration, and secondary skin infections.1 The face, genitalia, anus, and intertriginous areas of skin are at increased risk of dermatitis.1, 4, 11 Dosage adjustment or interruption of therapy may be required (see Dosage and Administration: Dosage).1, 7 Topical emollients, oral antihistamines, and topical corticosteroids have been used to treat dermatitis associated with topically applied mechlorethamine.3, 7, 11
Nonmelanoma skin cancer was reported during treatment or during one year of posttreatment follow-up in 4% of patients enrolled in a clinical trial comparing mechlorethamine gel with an extemporaneously compounded mechlorethamine ointment.1 Nonmelanoma skin cancer occurred in 2 or 6% of patients receiving treatment with mechlorethamine gel or mechlorethamine ointment, respectively.1 Some of the patients who developed nonmelanoma skin cancer previously had received therapies known to cause such cancers.1 Patients should be monitored for nonmelanoma skin cancer, which may occur on any area of the skin (including untreated areas), during and after treatment with topical mechlorethamine.1
Fetal/Neonatal Morbidity and Mortality
Mechlorethamine can cause fetal harm when administered to a pregnant woman.1 Malformations have been reported in children born to women who received systemically administered mechlorethamine during pregnancy.1 In addition, growth retardation and teratogenic and embryolethal effects were observed after subcutaneous administration of a single mechlorethamine dose in animals, and embryofetal toxicity is expected based on the drug's mechanism of action.1 Women should be advised to avoid pregnancy while receiving topical mechlorethamine therapy.1 If mechlorethamine is used during pregnancy or if the patient becomes pregnant during treatment, the patient should be apprised of the potential hazard to the fetus.1
Like other alcohol-based preparations, mechlorethamine gel is flammable.1 Application instructions should be followed carefully (see Dosage and Administration: Administration).1
Category D.1 (See Users Guide and see Fetal/Neonatal Morbidity and Mortality under Cautions: Warnings/Precautions.)
It is not known whether mechlorethamine is distributed into human milk.1 Because of the potential for topical or systemic exposure to mechlorethamine through exposure to the mother's skin, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.1
Safety and efficacy of mechlorethamine gel in pediatric patients have not been established.1
Among patients receiving mechlorethamine gel in a clinical trial, a reduction of 50% or more in Composite Assessment of Index Lesion Severity (CAILS) score was reported in 44% of patients 65 years of age or older compared with 66% of younger patients.1 Adverse cutaneous reactions and adverse effects requiring drug discontinuance were reported in 70 and 38%, respectively, of patients 65 years of age or older receiving mechlorethamine gel compared with 58 and 14%, respectively, of younger patients receiving the gel.1
Adverse effects reported in 5% or more of patients receiving mechlorethamine hydrochloride gel include dermatitis,1, 3 pruritus,1 laboratory abnormalities (anemia, neutropenia, thrombocytopenia),1 bacterial skin infection,1 skin ulceration or blistering,1 and skin hyperpigmentation.1
Drug interaction studies with mechlorethamine hydrochloride gel have not been performed to date.1 The manufacturer states that systemic exposure has not been observed in patients receiving the drug topically and that systemic drug interactions are unlikely.1
Mechlorethamine hydrochloride, a nitrogen mustard-derivative alkylating agent, is an antineoplastic agent.1, 3, 4 The mechanism of action of topical mechlorethamine in the treatment of mycosis fungoides-type cutaneous T-cell lymphoma (CTCL) is uncertain; some experts have postulated that the effects of topical mechlorethamine may not be related solely to its alkylating action and that immune mechanisms may be involved.4 Mechlorethamine was undetectable in plasma following topical administration of mechlorethamine 0.016% gel once daily for one month.1 In addition, mechlorethamine and half-mustard were undetectable in plasma after 2, 4, or 6 months of daily treatment with a 0.032% mechlorethamine gel.1, 7
Importance of reading manufacturer's patient information (e.g., medication guide) before starting mechlorethamine gel therapy and of reviewing this information each time the prescription is renewed.1
Importance of advising patients to store mechlorethamine gel in the original box in the refrigerator out of the reach of children and away from food.1 Importance of patients contacting a pharmacist before use if mechlorethamine gel is left at room temperature for longer than 1 hour per day.1 Importance of advising patients to discard any unused gel after 60 days.1
Importance of strict adherence to the recommended instructions for use and administration precautions from the manufacturer (see Dosage and Administration: Administration).1
Importance of advising patients to wash their hands thoroughly with soap and water after handling or applying mechlorethamine.1
Risk of adverse effects (e.g., dermatitis, mucosal injury, secondary cancers) from secondary exposure to topical mechlorethamine; importance of avoiding direct skin contact in individuals other than the patient.1 Importance of instructing caregivers to wear disposable nitrile gloves while applying mechlorethamine to patients and to wash their hands thoroughly with soap and water after removal of the gloves.1 Importance of caregivers taking appropriate measures if accidental skin exposure occurs (see Dosage and Administration: Administration).1 Importance of disposing of used gloves and any unneeded or used containers of the drug in a manner that prevents exposure of others.1
Risk of adverse ocular effects (e.g., pain, burns, inflammation, photophobia, blurred vision, blindness, severe irreversible injury) if eye exposure occurs; importance of advising patients to avoid eye contact and to take appropriate measures if accidental eye contact occurs (see Mucosal or Eye Injury under Cautions: Warnings/Precautions).1
Risk of adverse effects (e.g., pain, erythema, ulceration), possibly severe, if contact with mucous membranes occurs; importance of advising patients to avoid mucosal contact and to take appropriate measures if accidental mucosal contact occurs (see Mucosal or Eye Injury under Cautions: Warnings/Precautions).1
Importance of advising patients of risk of dermatitis, including increased risk on face, genitalia, anus, and intertriginous areas of skin.1 Importance of advising patients to contact clinician if symptoms of dermatitis occur.1
Importance of advising patients of risk of nonmelanoma skin cancer.1 Importance of advising patients to notify clinician of any new skin lesions and to undergo periodic assessment for signs and symptoms of skin cancer.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Necessity of advising women to avoid pregnancy and not to breast-feed during therapy.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Topical | Gel | 0.016% (of mechlorethamine) | Valchlor® | Helsinn |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions May 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Actelion Pharmaceuticals US, Inc. Valchlor® (mechlorethamine) gel prescribing information. South San Francisco, CA; 2013 Sep.
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3. Lessin SR, Duvic M, Guitart J et al. 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 Dermatol . 2013; 149:25-32. [PubMedCentral][PubMed 23069814]
4. Kim YH, Martinez G, Varghese A et al. Topical nitrogen mustard in the management of mycosis fungoides: update of the Stanford experience. Arch Dermatol . 2003; 139:165-73. [PubMed 12588222]
5. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: Non-Hodgkin's lymphomas. Version 2.2014. Available at the NCCN website. Accessed 2014 Jul 2. [Web]
6. Mycosis fungoides and the Sézary syndrome treatment (PDQ®). From: PDQ Physician data query (database). Bethesda, MD: National Cancer Institute; 2014 Jan 24. Accessed 2014 Aug 7. [Web]
7. US Food and Drug Administration. Center for Drug Evaluation and Research. Application Number 202317Orig1s000: Risk assessment and risk mitigation review(s). From FDA website. Accessed 2014 Aug 5. [Web]
8. Whittaker SJ, Marsden JR, Spittle M et al. Joint British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous T-cell lymphomas. Br J Dermatol . 2003; 149:1095-1107. [PubMed 14696593]
9. Willemze R, Dreyling M, ESMO Guidelines Working Group. Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol . 2010; 21 Suppl 5:v177-80.
10. Olsen EA, Whittaker S, Kim YH et al. 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. J Clin Oncol . 2011; 29:2598-607. [PubMedCentral][PubMed 21576639]
11. Kim YH. Management with topical nitrogen mustard in mycosis fungoides. Dermatol Ther . 2003; 16:288-98. [PubMed 14686971]
12. Reviewers' comments (personal observations) on Mechlorethamine Hydrochloride 10:00.
13. Ross WE, Chabner BA. Allergic reaction to cyclophosphamide in a mechlorethamine-sensitive patient. Cancer Treat Rep . 1977 May-Jun; 61:495-6.
14. Vonderheid EC. Topical mechlorethamine chemotherapy. Considerations on its use in mycosis fungoides. Int J Dermatol . 1984; 23:180-6. [PubMed 6373639]
15. Price NM, Hoppe RT, Deneau DG. Ointment-based mechlorethamine treatment for mycosis fungoides. Cancer . 1983; 52:2214-9. [PubMed 6640491]
16. Vonderheid EC, Van Scott EJ, Wallner PE et al. A 10-year experience with topical mechlorethamine for mycosis fungoides: comparison with patients treated by total-skin electron-beam radiation therapy. Cancer Treat Rep . 1979; 63:681-9. [PubMed 109206]
17. Van Scott EJ, Grekin DA, Kalmanson JD et al. Frequent low doses of intravenous mechlorethamine for late-stage mycosis fungoides lymphoma. Cancer . 1975; 36:1613-8. [PubMed 1192353]
18. Van Scott EJ, Kalmanson JD. Complete remissions of mycosis fungoides lymphoma induced by topical nitrogen mustard (HN2). Control of delayed hypersensitivity to HN2 by desensitization and by induction of specific immunologic tolerance. Cancer . 1973; 32:18-30. [PubMed 4577503]
19. Price NM, Hoppe RT, Constantine VS et al. The treatment of mycosis fungoides: adjuvant topical mechlorethamine after electron beam therapy. Cancer . 1977; 40:2851-3. [PubMed 412580]
20. Price NM, Constantine VS, Hoppe RT et al. Topical mechlorethamine therapy for mycosis fungoides. Br J Dermatol . 1977; 97:547-50. [PubMed 588466]
21. Ramsay DL, Halperin PS, Zeleniuch-Jacquotte A. Topical mechlorethamine therapy for early stage mycosis fungoides. J Am Acad Dermatol . 1988; 19:684-91. [PubMed 3183094]
22. Vonderheid EC, Tan ET, Kantor AF et al. Long-term efficacy, curative potential, and carcinogenicity of topical mechlorethamine chemotherapy in cutaneous T cell lymphoma. J Am Acad Dermatol . 1989; 20:416-28. [PubMed 2537348]