胚胎 - 胎儿毒性：可引起胎儿造成伤害。告知潜在危险的妇女胎儿易燃凝胶：VALCHLOR是酒精类凝胶。避免引起火灾，火焰，吸烟，直到凝胶已干
Valchlor (mechlorethamine) gel 0.016% is applied topically once a day to affected areas of the skin. Valchlor is the first and only FDA-approved topical formulation of mechlorethamine.
In the US, Valchlor gel 0.016% is indicated for the topical treatment of stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) in patients who have received prior skin-directed therapy.
Regulatory review with the European health authorities is ongoing.
AVAILABLE CLINICAL DATA
The efficacy of Valchlor was assessed in a randomized, multicenter, observer-blind, non-inferiority trial of 260 patients. Patients were stratified based on Stage (IA vs IB and IIA) and then randomized to receive Valchlor gel 0.016% w/w of mechlorethamine (equivalent to 0.02% mechlorethamine HCl) or Aquaphor®-based mechlorethamine HCl 0.02% ointment (compounded mechlorethamine). Patients had received at least one prior skin-directed therapy. Qualifying prior therapies included topical corticosteroids, phototherapy, Targretin® gel, and topical nitrogen mustard. Patients were not required to be refractory to or intolerant of prior therapies. Treatments were applied topically on a daily basis for 12 months.
60% of the patients on the Valchlor arm and 48% of patients on the comparator arm achieved a response based on the Composite Assessment of Index Lesion Severity (CAILS) score. Valchlor was non-inferior to the comparator based on a CAILS overall response rate ratio of 1.24 (95% CI 0.98, 1.58). Complete responses constituted a minority of the CAILS or Severity Weighted Assessment Tool (SWAT) overall responses. The onset of CAILS overall response for both treatment arms showed a wide range from 1 to 11 months.
The most common adverse reactions (≥5%) were dermatitis (56%), pruritus (20%), bacterial skin infection (11%), skin ulceration or blistering (6%), and skin hyperpigmentation (5%). These reactions may be moderately severe or severe. Elderly patients aged 65 and older may be more susceptible. Depending on severity, treatment reduction, suspension, or discontinuation may be required.
Mechlorethamine 0.016%; topical gel; contains propylene glycol, isopropyl alcohol.
Treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy.
Mechlorethamine, also known as nitrogen mustard, is an alkylating agent which inhibits rapidly proliferating cells.
The efficacy of Valchlor was assessed in a randomized, multicenter, observer-blind, active-controlled, non-inferiority clinical trial involving 260 patients with Stage IA, IB, and IIA mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) who had received ≥1 prior skin-directed therapy (eg, topical corticosteroids, phototherapy, Targretin gel, or topical nitrogen mustard). Patients were not required to be refractory to or intolerant of prior therapies.
Patients were randomized (after stratification based on Stage IA vs. IB and IIA) to receive Valchlor (N=119) or Aquaphor-based ointment (N=123), both equivalent to 0.02% mechlorethamine. The study drug was to be topically applied once daily for 12 months, and concomitant use of topical corticosteroids was not permitted.
Patients were evaluated monthly for the first 6 months, then every 2 months for the last 6 months using the Composite Assessment of Index Lesion Severity (CAILS) score. A response was defined as ≥50% reduction in baseline CAILS score, which was confirmed at the next visit ≥4 weeks later; a complete response was defined as a confirmed CAILS score of 0.
Patients were also evaluated using the Severity Weighted Assessment Tool (SWAT). A response was defined as ≥50% reduction in baseline SWAT score, which was confirmed at the next visit ≥4 weeks later.
At 12 months, 60% of patients treated with Valchlor and 48% of patients treated with the comparator achieved a response based on CAILS score. Valchlor was non-inferior to the comparator based on a CAILS overall response ratio of 1.24 (95% CI 0.98, 1.58). Complete responses constituted a minority of the CAILS or SWAT overall responses. The onset of CAILS overall response for both treatment arms showed a wide range from 1 to 11 months.
Apply a thin film once daily to affected areas of the skin. Apply to completely dry skin ≥4 hours before or 30 minutes after showering or washing. Allow treated areas to completely dry for 5–10 minutes after applying. Wash hands thoroughly after application. Discontinue if any grade of skin ulceration, blistering, or moderately-to-severe, or severe dermatitis occur; restart at reduced frequency of once every 3 days upon improvement; if reintroduction is tolerated for at least 1 week, can increase to every other day for 1 week and then once daily if tolerated.
Mucosal (oral, nasal) or eye exposure; blindness and severe irreversible anterior eye injury may occur; immediately irrigate for ≥15 minutes with copious amounts of water. Secondary exposure; avoid direct skin contact with patient. Risk of dermatitis (eg, face, genitalia, anus, and intertriginous skin); monitor for redness, swelling, inflammation, itchiness, blisters, ulceration, and secondary skin infections. Monitor for nonmelanoma skin cancer during and after treatment. Flammable (avoid fire and flame until gel has dried). Pregnancy (Category D); may cause fetal harm. Nursing mothers: not recommended.
Dermatitis, pruritus, bacterial skin infection, skin ulceration or blistering, hyperpigmentation.