General Information

Valchlor is a gel formulation of mechlorethamine, an alkylating agent that inhibits rapidly proliferating cells.

Valchlor is specifically indicated for the topical treatment of stage IA and IB mycosisfungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy.

Mechanism of Action

Valchlor is a gel formulation of mechlorethamine, also known as nitrogen mustard, an alkylating agent that inhibits rapidly proliferating cells.

Side Effects

Adverse events associated with the use of Valchlor may include, but are not limited to, the following:

• dermatitis
• pruritus
• bacterial skin infection
• skin ulceration or blistering
• hyperpigmentation

Dosing/Administration

Valchlor is supplied as a gel for topical administration. The recommendation is to apply a thin film of Valchlor gel once daily to affected areas of the skin. Upon improvement, treatment with Valchlor can be restarted at a reduced frequency of once every three days. If reintroduction of treatment is tolerated for at least one week, the frequency of application can be increased to every other day for at least one week and then to once daily application if tolerated.

Clinical Trial Results

The FDA approval of Valchlor gel was based on a randomized, multicenter, observer-blind, active-controlled, non-inferiority clinical trial of 260 subjects with stage IA, IB, and IIA mycosisfungoides-type cutaneous T-cell lymphoma (CTCL) who had received at least one prior skin-directed therapy. The subjects were stratified based on stage (IA versus IB and IIA) and then randomized to receive Valchlor 0.016 percent (equivalent to 0.02 percent mechlorethamine HCl) or Aquaphor-based mechlorethamine HCl 0.02 percent ointment (Comparator). Eighteen subjects were excluded from the efficacy analysis due to protocol violations involving randomization at a single site. Study drug was applied topically on a daily basis for 12 months. Concomitant use of topical corticosteroids was not permitted during the study. The mean daily usage of Valchlor gel was 2.8 g. The maximum daily usage was 10.5 g. Subjects were evaluated for a response on a monthly basis for the first six months and then every two months for the last six months using the Composite Assessment of Index Lesion Severity (CAILS) score. A response was defined as greater than or equal to 50 percent reduction in baseline CAILS score, which was confirmed at the next visit at least four weeks later. A complete response was defined as a confirmed CAILS score of 0 (no symptoms). Subjects were also evaluated using the Severity Weighted Assessment Tool (SWAT). A response was defined as greater than or equal to 50 percent reduction in baseline SWAT score, which was confirmed at the next visit at least four weeks later. Sixty percent (60 percent) of the subjects on the Valchlor arm and 48 percent of subjects on the comparator arm achieved a response based on the CAILS score. Valchlor was not inferior to the comparator based on a CAILS overall response rate ratio of 1.24. 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 one to 11 months.