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Panniculitis With Arthralgia in Patients With Melanoma Treated With Selective BRAF Inhibitors and Its Management [Observation]
Zimmer, L., Livingstone, E., Hillen, U., Domkes, S., Becker, A., Schadendorf, D. Mon, 16 Jan 2012 12:41:59 -0800
Background  Painful lobular panniculitis appears to be a novel cutaneous adverse effect of selective BRAF inhibitors. Observation  We report the clinical course and management in 2 women with metastatic melanomas harboring the BRAFV600E mutation, who developed panniculitis with arthralgia during therapy with selective oral BRAF inhibitors. Panniculitis with arthralgia was the acute presenting adverse effect in both patients. Painful, red, nodular lesions were located on the upper and lower extremities. Biopsy specimens of the nodules showed a mild, predominantly lobular neutrophilic panniculitis. Analgesic and anti-inflammatory treatment improved panniculitis and arthralgia in both cases. It was also necessary to reduce the BRAF inhibitor dose in 1 patient. Conclusions  During therapy with selective BRAF inhibitors, panniculitis with arthralgia represents a new adverse effect that can require dose reduction. In case of this adverse effect, treatment with nonsteroidal anti-inflammatory drugs, such as etoricoxib, should be initiated early to keep patients on treatment and to avoid drug discontinuation and tumor progression.
Phase I Clinical Trial of O6-Benzylguanine and Topical Carmustine in the Treatment of Cutaneous T-Cell Lymphoma, Mycosis Fungoides Type [Study]
Apisarnthanarax, N., Wood, G. S., Stevens, S. R., Carlson, S., Chan, D. V., Liu, L., Szabo, S. K., Fu, P., Gilliam, A. C., Gerson, S. L., Remick, S. C., Cooper, K. D. Mon, 16 Jan 2012 12:41:48 -0800
Objectives  To evaluate the toxic effects and maximum tolerated dose of topical carmustine [1,3-bis (2-chloroethyl)-1-nitrosourea] following intravenous O6-benzylguanine in the treatment of cutaneous T-cell lymphoma (CTCL), and to determine pharmacodynamics of O6-alkylguanine DNA alkyltransferase activity in treated CTCL lesions. Design  Open-label, dose-escalation, phase I trial. Setting  Dermatology outpatient clinic and clinical research unit at a university teaching hospital. Patients  A total of 21 adult patients (11 male, 10 female) with early-stage (IA-IIA) refractory CTCL, mycosis fungoides type, treated with topical carmustine following intravenous O6-benzylguanine. Intervention  Treatment once every 2 weeks with 120 mg/m2 intravenous O6-benzylguanine followed 1 hour later by whole-body, low-dose topical carmustine starting at 10 mg, with 10-mg incremental dose-escalation in 3 patient cohorts. Cutaneous T-cell lymphoma lesional skin biopsy specimens were taken at baseline and 6 hours, 24 hours, and 1 week after the first O6-benzylguanine infusion for analysis of O6-alkylguanine-DNA alkyltransferase activity. Main Outcome Measures  Clinical response measured by physical examination and severity-weighted assessment tool measurements, safety data acquired by review of adverse events at study visits, and O6-alkylguanine-DNA alkyltransferase activity in treated lesion skin biopsy specimens. Results  A minimal toxic effect was observed through the 40-mg carmustine dose level with 76% of adverse events being grade 1 based on the National Cancer Institute Common Terminology Criteria for Adverse Events. Mean baseline O6-alkylguanine-DNA alkyltransferase activity in CTCL lesions was 3 times greater than in normal controls and was diminished by a median of 100% at 6 and 24 hours following O6-benzylguanine with recovery at 1 week. Clinical disease reduction correlated positively with O6-alkylguanine-DNA alkyltransferase activity at 168 hours (P = .02) and inversely with area under the curve of O6-alkylguanine-DNA alkyltransferase over 1 week (P = .01). Twelve partial responses and 4 complete responses were observed (overall response, 76% [95% CI, 0.55-0.89]). Five patients discontinued therapy owing to adverse events with a possible, probable, or definite relationship to the study drug. Conclusion  O6-benzylguanine significantly depletes O6-alkylguanine-DNA alkyltransferase in CTCL lesions and in combination with topical carmustine is well tolerated and shows meaningful clinical responses in CTCL at markedly reduced total carmustine treatment doses. Trial Registration  clinicaltrials.gov Identifier: NCT00003613
Trends in Melanoma Mortality Among Non-Hispanic Whites by Educational Attainment, 1993-2007 [Study]
Cokkinides, V. E., Geller, A. C., Jemal, A. Mon, 16 Jan 2012 12:41:37 -0800
Objective  To evaluate overall Subscribe to Dermatology RSS feed