UPDATED August 29, 2013 — A new proprietary gel formulation of mechlorethamine (Valchlor, Ceptaris Therapeutics Inc.) has been approved by the US Food and Drug Administration (FDA) for use in the topical treatment of stage IA and IB mycosis-fungoides-type cutaneous T-cell lymphoma (CTCL) in patients who have already received skin-directed therapy.
Mechlorethamine, commonly known as nitrogen mustard, is already approved for intravenous use in the treatment of mycosis fungoides.
Mycosis fungoides is the most common type of cutaneous T-cell lymphoma, which typically begins with scaly red patches and plaques in the skin that can progress to form thicker plaques/nodules and disfiguring tumors. Most cases are diagnosed at an early stage (stages IA and IB), but they can be confused with other skin conditions until a skin biopsy provides a definitive diagnosis.
The topical use of the product is recommended as primary treatment for early-stage CTCL by the National Comprehensive Cancer Network (NCCN), but until now, there have been no FDA-approved formulations, Ceptaris Therapeutics noted in a press release. Only nonstandardized pharmacy-compounded petroleum ointment or aqueous-based topical preparations were available, and there was no requirement for these to be reviewed by the FDA.
"The use of topical mechlorethamine has been documented over several decades, but this is the first time that a product has gone through the rigorous FDA process," noted Stuart R. Lessin MD, former director of dermatology at the Fox Chase Cancer Center in Philadelphia, president of the board of directors at the Cutaneous Lymphoma Foundation, and principal investigator of the clinical trial on which approval of the new product was based.
That trial, published earlier this year in JAMA Dermatology (2013;149:25-32), involved 260 patients with early-stage mycosis-fungoides-type CTCL. The inclusion criteria included stage IA to IIA disease, but the "vast majority" of patients had stage IA or IB disease, the company noted. Patients had received at least 1 previous skin-directed therapy, which could have included topical corticosteroids, phototherapy, Targretin gel, or topical nitrogen mustard (mechlorethamine), but they were not required to be refractory to or intolerant of other therapies.
The noninferiority trial compared the proprietary gel formulation with a pharmacy-compounded preparation, and the end point was a confirmed complete response at 6 months, defined as at least a 50% reduction in the Composite Assessment of Index Lesion Severity score. This was achieved by 60% of patients treated with the proprietary gel but by only 48% of those treated with the pharmacy-compounded product.
The pharmacy-compounded product used was an petroleum-based ointment, noted the study's senior author, Youn Kim, MD, who is the Joanne and Peter Haas Jr Professor for Cutaneous Lymphoma Research and director of the multidisciplinary cutaneous lymphoma program at Stanford University in California.
However, different pharmacies use different methods to compound the ointment, so quality varies, she noted. She has also heard from patients that they have been issued aqueous preparations, which are inappropriate because nitrogen mustard is unstable in water and becomes inactivated, she explained in an interview.
Having an anhydrous product that is manufactured under quality-controlled conditions and has passed rigorous FDA review is a "victory for patients," Dr. Kim told Medscape Medical News.
"After many decades, patients now have a reliable product of consistent quality," and the cost of treatment will be contained, she explained. And because topical mechlorethamine is considered a standard of care in NCCN guidelines and because the gel is approved by the FDA, it should be covered by medical insurance.
This is not the case for pharmacy-compounded products; for the most part, patients pay for these themselves, and prices can vary widely because individual pharmacies price the products based on the labor involved when they compound the product, she added.
The new gel is indicated as primary treatment for the majority of patients with this disease — those with stage IA or IB mycosis fungoides-type CTCL, Dr. Kim noted.
Mycosis fungoides is a rare form of non-Hodgkin's lymphoma, but accounts for about 70% to 80% of CTCL. Around two thirds of patients present with stage IA or IB disease and, provided the skin disease is well controlled, a majority of patients stay in stage I and do not progress.
"They live with this chronic skin condition," Dr. Kim explained. Stage I disease is not life-threatening, but its effects on quality of life "should not be underestimated." Although effective therapy can control symptoms, the disease can cover substantial areas of the body and can cause itching.
In the remaining one third of patients, however, mycosis-fungoides-type CTLC presents at a more advanced stage (stages IIB to IV), when tumor lesions are visible on the skin or erythema is generalized (erythroderma). By then, there is a risk that the disease will spread to the lymph nodes, peripheral blood, and visceral organs, Dr. Kim explained. In a small subset of patients, even those with early-stage disease (stages I to IIA), extracutaneous disease can develop.
The safety information for the product notes that the most common adverse reaction is contact dermatitis, which is usually mild and very manageable but in some cases can be severe and require dosing changes or discontinuation. Contact with mucous membranes, especially the eyes, must be avoided. The proprietary product is an alcohol-based gel and, as for all such products, patients are warned to avoid fire, flame, and smoking until the gel has dried on the skin.
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Cite this: First Proprietary Gel Product for Cutaneous Lymphoma - Medscape - Aug 27, 2013.