Dermatologic Toxicities Associated with Chronic Gamma-Secretase Inhibitor Treatment for Desmoid Tumor

    April 2017 in “ ˜The œjournal of investigative dermatology/Journal of investigative dermatology ”
    Therese Woodring, Geraldine O’Sullivan-Coyne, A. Chen, H.H. Kong
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    TLDR Most patients experienced mild to moderate skin problems during a trial for a desmoid tumor treatment.
    In a phase II trial involving 17 patients with desmoid tumors, 71% experienced adverse skin events while being treated with the gamma-secretase inhibitor PF-03084014. The trial, conducted at NCI/NIH, aimed to investigate the role of Notch signaling, affected by gamma-secretase, in skin toxicities. Patients were administered 150mg of PF orally twice daily for 21 days per cycle. Dermatologic toxicities included follicular and cystic lesions in 53% of patients and pruritic eruptions in 35%, all of which were grade 1 or 2. Of the 7 patients evaluated by dermatology, 6 had recurrent inflammatory lesions in intertriginous areas, and there were cases of granuloma annulare and urticarial plaques. Management involved topical therapies, systemic antibiotics, and in some cases, surgical intervention. One patient discontinued PF due to urticaria. The median follow-up time was over 25 months, with 10 patients on therapy for more than 2 years. The study suggests that further research on gamma-secretase could enhance understanding of Notch signaling in skin and follicular diseases.
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