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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-13924

Dummer, R; Hauschild, A; Becker, J C; Grob, J J; Schadendorf, D; Tebbs, V; Skalsky, J; Kaehler, K C; Moosbauer, S; Clark, R; Meng, T C; Urosevic, M (2008). An exploratory study of systemic administration of the toll-like receptor-7 agonist 852A in patients with refractory metastatic melanoma. Clinical Cancer Research, 14(3):856-864.

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Abstract

PURPOSE: A topical Toll-like receptor 7 (TLR7) agonist induces regression of cutaneous melanocytic neoplasms. We explored antitumor activity of a systemically administered TLR7 agonist, 852A, in patients with metastatic melanoma. EXPERIMENTAL DESIGN: We undertook a phase II, multicenter, open-label study in patients with chemotherapy-refractory metastatic melanoma. Patients received i.v. 852A, starting at 0.6 mg/m(2) and increasing to 0.9 mg/m(2) based on tolerance, thrice per week for 12 weeks. Clinical response was determined by Response Evaluation Criteria in Solid Tumors. Immune effects of 852A were monitored by measuring serum type I IFN and IP-10 together with assessment of immune cell markers in peripheral blood. RESULTS: Twenty-one patients were enrolled. Thirteen patients completed the initial 12-week treatment cycle, with two discontinuing for adverse events considered to be possibly related to study drug. Four (19%) patients had disease stabilization for >100 days. One patient had a partial remission after two treatment cycles, but progressed during the third. Dose-limiting toxicity was observed in two patients. Serum type I IFN and IP-10 increased in most patients on 852A administration. Serum type I IFN increases were greater after dosing with 852A 0.9 mg/m(2) than after 0.6 mg/m(2) (P = 0.009). The maximal increase in IP-10 compared with baseline correlated with the maximal increase in type I IFN (P = 0.003). In the eight patients with immune cell marker data, CD86 expression on monocytes increased significantly post-first dose (P = 0.007). CONCLUSION: Intravenous 852A was well tolerated and induced systemic immune activation that eventually resulted in prolonged disease stabilization in some patients with stage IV metastatic melanoma who had failed chemotherapy.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
DDC:610 Medicine & health
Language:English
Date:February 2008
Deposited On:18 Feb 2009 15:31
Last Modified:27 Nov 2013 18:31
Publisher:American Association for Cancer Research
ISSN:1078-0432
Publisher DOI:10.1158/1078-0432.CCR-07-1938
PubMed ID:18245549

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