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CORRESPONDENCE
Year : 2020  |  Volume : 65  |  Issue : 3  |  Page : 237-239
Mechlorethamine gel usage in patients with mycosis fungoides in a lymphoma clinic


From the Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, USA

Date of Web Publication14-Apr-2020

Correspondence Address:
Joya Sahu
Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.IJD_433_18

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How to cite this article:
Duffy R, Jennings T, Sahu J. Mechlorethamine gel usage in patients with mycosis fungoides in a lymphoma clinic. Indian J Dermatol 2020;65:237-9

How to cite this URL:
Duffy R, Jennings T, Sahu J. Mechlorethamine gel usage in patients with mycosis fungoides in a lymphoma clinic. Indian J Dermatol [serial online] 2020 [cited 2020 Nov 27];65:237-9. Available from: https://www.e-ijd.org/text.asp?2020/65/3/237/282459




Sir,

Mechlorethamine gel functions as an antineoplastic therapy via three unique mechanisms: attachment of alkyl groups to DNA bases, resulting in fragmentation and cell death, DNA damage via the formation of cross-links, and induction of mispairing of nucleotides leading to mutation.[1] Mechlorethamine, or nitrogen mustard, was traditionally used as a wartime gas, but in 1940s, it was compounded into a petrolatum-based topical ointment and was used as one of the earliest forms of topical antineoplastic therapies.[2] Mechlorethamine gel was approved by the Food and Drug Administration (FDA) in 2013.

At the Jefferson Multi-Disciplinary Cutaneous Lymphoma Clinic (MCLC), mechlorethamine gel (0.016%) is used as a primary treatment modality, for maintenance therapy after patients receive systemic or radiation therapy, and as an adjuvant therapy. The method in which we choose to utilize mechlorethamine gel is based on disease burden and staging.

Mechlorethamine gel is often used as an adjuvant therapy with both topical and systemic therapies. Mechlorethamine gel is used in combination with topical treatment for a skin-directed synergistic effect and used in combination with systemic treatment for patients with lymph node, blood, or visceral organ involvement. For the additive skin-directed effects, adjuvant mechlorethamine gel has been used in combination with class one topical steroids, narrowband ultraviolet B (NBUVB), psoralen and ultraviolet A (PUVA), imiquimod, or pimecrolimus.

Mechlorethamine gel can be used for any type of MF provided the lesions are not open and weeping and not in mucosal or intertriginous areas.

Providers at the Jefferson MCLC utilize a specific approach for the timeline in which mechlorethamine gel should be applied. This is a two-tiered approach based on whether the treatment is initiated to treat active lesions or maintain disease clearance. Patients are directed to apply mechlorethamine gel based on disease burden and patient tolerance. For those patients using mechlorethamine gel to treat active disease, providers advise applying mechlorethamine gel to the active lesions every other day, daily, or twice daily. When using mechlorethamine gel to maintain disease clearance, patients are advised to apply medication on a range from once to four times weekly, slowly uptitrating.

Patients are commonly prescribed topical steroids as a primary treatment before initiation of mechlorethamine gel. Though topical steroids are an appropriate initial treatment due to their efficacy and low rate of adverse events,[4] mechlorethamine gel is selected as an additional treatment modality when patients demonstrate progressive disease. The topical steroid is not discontinued as it takes care of the dermatitis induced by mechlorethamine.

There are certain areas of the body that have demonstrated greater susceptibility to the side effects of both mechlorethamine gel and topical steroids. The most sensitive areas are the intertriginous areas, face, genitalia, and anus. The risk for dermatitis from mechlorethamine gel and skin thinning increases in intertriginous areas due to thin skin, occlusion, and skin maceration. Therefore, providers in the MCLC do not typically use mechlorethamine gel or topical steroids in these areas, and alternatively administer pimecrolimus, a calcineurin inhibitor, at varying dosages. It is important to note that pimecrolimus and tacrolimus should not be used in areas actively affected by irritant dermatitis as this will cause severe burning and discomfort. Systemic absorption secondary to the use of mechlorethamine gel has not been demonstrated to be significant.

It is important to note that systemic absorption secondary to the use of mechlorethamine gel has not been demonstrated to be significant in previous studies. The randomized controlled trial resulting in FDA approval of the drug demonstrated no systematic pattern of change in any laboratory value measured, consistent with lack of systemic absorption.3 Furthermore, high-performance liquid chromatography serum assays performed revealed no detectable blood levels or evidence of systemic absorption of mechlorethamine.[3] Due to the low likelihood of systemic absorption, no investigations are recommended in order to monitor the systemic side effects.

The risk of nonmelanoma skin cancer (NMSC) secondary to the use of mechlorethamine gel in the Lessin et al. study was found not to be significant, as the few cases that were diagnosed commonly occurred on sun-exposed areas and in patients with a history of skin cancer or prior skin-directed therapies, including phototherapy.[3] We advise patients using mechlorethamine that they have the same risk of NMSC as those not applying the medicine. Sun avoidance and the use of sunscreen are paramount.

At the MCLC, we dedicate time ensuring that patients prescribed mechlorethamine gel understand how to store the medication and how and when to apply the medication.

Mechlorethamine gel is not stable in water; completely dry skin is essential in order for the medication to be absorbed and function correctly. Furthermore, patients are instructed to moisturize 2 hours before or 2 hours after application of the medication. Patients are instructed to wash their hands with soap immediately after application (unless they have disease on their hands in which case they can wash their hands 30 minutes post application, if so desired) and if any caregivers are applying the medication, they must wear disposable nitrile gloves.

In order for mechlorethamine gel to work appropriately, it must be stored in the refrigerator. Patients must apply the medication within 30 min of removal from the refrigerator and return it to the refrigerator immediately after use. If patients are traveling or do not have direct access to a refrigerator for an extended period of time, the manufacturer provides a cold pack for the patients in order to keep the medication at the appropriate temperature.

MF patients are assessed at each follow up visit for response to therapy. The first 3–4 weeks on mechlorethamine gel, the lesions will become more pronounced, erythematous, and weepy. After this point, the lesions responding to therapy will show vast improvement, leaving behind postinflammatory hyperpigmentation (PIH). The PIH must not be mistaken for patch stage MF. Non-response to therapy is the development of increased number of plaques or tumors, the evolution to erythroderma or the progression to significant blood involvement while on therapy. If patients are not responding to therapy or progressing, one can treat with the next line of appropriate therapy.

Mechlorethamine gel is a common medication for the treatment of mycosis fungoides. The Jefferson MCLC uses it as both a primary therapy for patch and plaque disease, adjunctive therapy, and as a prevention modality for patients in order to prolong clinical remission. We have found great success with this drug, which we attribute to careful attention to correct patient application and minimization of side effects, enhancing patient compliance.

Acknowledgements

We would like to acknowledge Mitch Finkelstein for his services in retrospective data collection.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Povirk LF, Shuker DE. DNA damage and mutagenesis induced by nitrogen mustards. Mutat Res 1994;318:205-26.  Back to cited text no. 1
    
2.
Kim YH, Martinez G, Varghese A, Hoppe RT. Topical nitrogen mustard in the management of mycosis fungoides: update of the Stanford experience. Arch Dermatol 2003;139:165-73.  Back to cited text no. 2
    
3.
Lessin SR, Duvic M, Guitart J, Pandya AG, Strober BE, Olsen EA, 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.  Back to cited text no. 3
    
4.
Zackheim HS, Kashani-Sabet M, Amin S. Topical corticosteroids for mycosis fungoides. Experience in 79 patients. Arch Dermatol 1998;134:949-54.  Back to cited text no. 4
    




 

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