Safety and efficacy of low-dose bexarotene and PUVA in the treatment of patients with mycosis fungoides.

BACKGROUND: The new rexinoid bexarotene is a retinoid X receptor antagonist and immune response modifier. Although combinations of oral bexarotene and psoralen plus UVA (PUVA) have been tried in patients with all stages of mycosis fungoides (MF), the dosage of bexarotene used in these combination regimens has been variable. OBJECTIVE: To assess the efficacy and safety of low-dose oral bexarotene and PUVA in patients with relapsed or treatment-refractory MF following monotherapy with multiple agents including PUVA, narrow-band UVB, interferon-alpha, oral bexarotene, and topical corticosteroids. METHOD: Combination therapy with PUVA three times weekly and low-dose oral bexarotene (150 or 300 mg/day, depending on physicians' preference) was administered to 14 patients, seven men and seven women (median age 49.5 years, range 30-75 years), with relapsed or refractory MF stages I-III. All responders received maintenance treatment at the same bexarotene dose that induced remission until progression or unacceptable toxicity. RESULTS: Low-dose oral bexarotene combined with PUVA was associated with an overall response rate (complete response or partial response) in 67% of the nine patients with refractory MF who completed the treatment course. Of these nine patients, four had a complete response, two had a partial response, one had stable disease, and two had progressive disease. Five patients withdrew because of hyperlipidemia. Oral bexarotene was continued as maintenance therapy in three of the four complete responders (one refused); two of these patients relapsed 2-10 months after PUVA discontinuation. Patients with partial response or stable disease received the combination for 3-5 months and were switched to another treatment regimen because of lack of further response. Therapy was fairly well tolerated. CONCLUSION: In a select population of patients who had not responded to at least one monotherapy for early-stage MF, a combination of low-dose oral bexarotene and PUVA was successful in achieving a satisfactory overall response rate in 67% of patients who completed the treatment course and was fairly well tolerated. Limitations of the study include the small number of patients evaluated, its retrospective nature, and the fact that patients were commenced on different bexarotene starting doses (150 or 300 mg/day), depending on physicians' preference.

Nasal provocation of patients with allergic rhinitis and the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Allergic rhinitis is a common problem involving activation of nasal mast cells and irritability. The hypothalamic-pituitary-adrenal (HPA) axis is stimulated in cases of emotional or environmental stress, and mast cells have been implicated in stress-induced immune responses. OBJECTIVE: To investigate whether intranasal challenge of patients allergic to a single antigen would stimulate the HPA axis. METHODS: Plasma corticotropin and cortisol levels were measured 20, 40, 60, 80, 100, and 120 minutes after intranasal antigen administration in healthy volunteers (n=3) and in patients with rhinitis who are allergic to Parietaria (n=10). RESULTS: Mean +/- SD corticotropin levels were 24.43 +/- 14.38 pg/mL in patients compared with 8.83 + 5.02 pg/mL in controls, and this increase was statistically significant (P = .049). Patient cortisol levels also increased to a mean +/- SD of 8.87 +/- 4.90 pg/mL (at 40 minutes) compared with 4.36 +/- 1.72 pg/mL in controls (P = .11 due to 1 outlier). Compared with individual patient prechallenge levels, corticotropin levels increased in 7 patients and cortisol levels increased in 5 at 40 minutes. CONCLUSION: These results suggest that allergic rhinitis may activate the HPA axis. A larger study with additional controls is required for definitive conclusions.