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.
View at publisher
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.
62 downloads since deposited on 18 Feb 2009
20 downloads since 12 months
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic|
|Dewey Decimal Classification:||610 Medicine & health|
|Deposited On:||18 Feb 2009 15:31|
|Last Modified:||27 Nov 2013 18:31|
|Publisher:||American Association for Cancer Research|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page