peldesine and Lymphoma--T-Cell--Cutaneous

The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor.. We attempted to determine the efficacy of peldesine (BCX-34) in a 1% dermal cream formulation as a treatment for cutaneous T-cell lymphoma (CTCL).. Ninety patients with patch and plaque phase CTCL, histologically confirmed by a referee dermatopathologist, were enrolled in a randomized, double-blind, placebo-controlled study. BCX-34 dermal cream 1% or the vehicle cream (as a placebo control) was applied twice daily to the entire skin surface for up to 24 weeks. Efficacy of the topical therapy was assessed in terms of complete or partial (> or = 50%) clearing of patches and plaques.. Of the 89 patients able to be examined, 43 received BCX-34 and 46 received the placebo vehicle cream. One patient withdrew early and was not analyzed. The two groups were well balanced for potential prognostic factors. A total of 28% (12/43) of the patients treated with BCX-34 showed a response, but 24% (11/46) of patients who received vehicle also responded (P =.677).. Although BCX-34 dermal cream 1% was not significantly better than the control as therapy for patch and plaque-phase CTCL, this appears to be the first published placebo-controlled trial evaluating treatment for CTCL. Whether the vehicle cream has more than a placebo therapeutic effect is unclear. The relatively high (24%) placebo response rate should be kept in mind in assessing other treatments for early-stage CTCL.

Topics: Administration, Cutaneous; Adult; Aged; Double-Blind Method; Enzyme Inhibitors; Female; Guanine; Humans; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Placebos; Treatment Outcome

9-(3-Pyridylmethyl)-9-deazaguanine (BCX-34), a new purine nucleoside phosphorylase inhibitor, has selective immunosuppressive activity with potential therapeutic value in T-cell-mediated disease. We now report a sensitive, specific and reproducible method for measurement of 9-(3-pyridylmethyl)-9-deazaguanine in biological fluids using high-performance liquid chromatography (HPLC). 9-(3-Pyridylmethyl)-9-deazaguanine was extracted from plasma using perchloric acid precipitation followed by passage through Sep-Pak C18 cartridges (average extraction efficiency, 64.6%). Standard curves were linear over the range of interest (28-1120 ng/ml in plasma and 200-4000 ng/ml in urine, r2 > 0.999). Within-day and between-day coefficients of variation were less than 8%. The limit of quantitation was 28 ng/ml in plasma and 200 ng/ml in urine. This HPLC method should be useful in future clinical studies with this drug.

Topics: Administration, Oral; Chromatography, High Pressure Liquid; Guanine; Humans; Immunosuppressive Agents; Infusions, Intravenous; Lymphoma, T-Cell, Cutaneous; Purine-Nucleoside Phosphorylase; Reproducibility of Results; Sensitivity and Specificity; Skin Neoplasms