Carmustine BCNU

Introduction

Carmustine is a nitrosourea agent that serves as an alternative cytostatic drug for the local therapy of patch/thin plaque type CTCL. It was introduced into the therapeu tic armamentarium for CTCL by Zackheim (54-56). Like HN2, BCNU preparations can be applied topically to the entire skin surface.

Mode of Action

The BCNU is an alkylating agent exhibiting cytostatic effects. Indications

Whereas PUVA and topical HN2 are the most frequent treatment modalities for the management of patch/thin plaque stage of lymphoproliferative disorders, BCNU has its major indication when these techniques cannot be used for either geographical reasons (PUVA not available within a reasonable distance) or in cases of allergic hypersensitivity against HN2.

Practical Application

The stock solution is prepared by dissolving 100 mg BCNU powder (Bristol Laboratories) in 50 ml of 95% or absolute alcohol, yielding a concentration of 2mg/mL. This stock solution is stable at a temperature of 2-8°C in the refrigerator for at least 3 months. In order to prepare the solution for the treatment of lesions, 5 mL of the stock solution (corresponding to 10 mg of BCNU) is added to 60 mL of cool tap water (57). The resulting aqueous solution is unstable and should be used immediately. The solution is applied once daily (58) for 8-10 weeks to the general body surface with exception of the head, genitals, body folds, palms and soles unless they are involved. If large areas are clearly uninvolved, they need not be treated. Total dose applied should not exceed 200-600 mg BCNU, even though cumulative doses of 6700 mg have been reached in occasional patients (59).

For spot therapy an ointment preparation (4 mg/gm BCNU in white petrolatum) is easier to use and causes fewer cutaneous reactions than the solution. Because of increased absorption, it may pose a greater hazard of myelosuppression (46).

Results

In a large series of patients with long term follow up (up to 15 years) treated with topical carmustine (BCNU), a complete response was obtained in 86% of those with limited extent (less than 10%) plaques (T1 stage), in 48% of those with extensive (greater than or equal to 10%) plaques (T2 stage), and in 21% of those with erythroderma. The median time to achieve complete response was 11.5 weeks (59).

Adverse effects include cutaneous irritation in most patients, telangiectases, hyperpigmentation and the potential for carcinogenesis. Mild hematopoietic depression may occur (less than 10% of patients (59)) and can be avoided by limiting the total dose of topical BCNU to less than 600 mg per course.

Combination with Other Modalities

Even though not explicitly reported, there should not be any contraindications against using topical glucocorticosteroids or systemic nonaggressive agents such as retinoids or interferons in combination with BCNU. There is no proven evidence for a synergistic beneficial effect of such combinations.

Comments

Carmustine is an alternative cytostatic drug for local therapy to HN2 with efficacy comparable to that of mechlorethamine hydrochloride or PUVA (56). The advantages are similar to HN2, except that a remission is generally achieved earlier than with HN2. Moreover carmustine can be used in patients allergic to mechlorethamine.

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