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Annals of Oncology Advance Access published online on January 17, 2006
Annals of Oncology, doi:10.1093/annonc/mdj138
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© 2006 European Society for Medical Oncology
Received October 6, 2005
Revised December 5, 2005
Accepted December 14, 2005

original article

Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG

D. Schadendorf 1 *, S. Ugurel 1, B. Schuler-Thurner 2, F. O. Nestle 3, A. Enk 4, E.-B. Bröcker 5, S. Grabbe 6, W. Rittgen 7, L. Edler 7, A. Sucker 1, C. Zimpfer-Rechner 1, T. Berger 2, J. Kamarashev 3, G. Burg 3, H. Jonuleit 4, A. Tüttenberg 4, J. C. Becker 5, P. Keikavoussi 5, E. Kämpgen 8, and G. Schuler 2

1 Skin Cancer Unit, German Cancer Research Center & University Hospital Mannheim, Mannheim, Germany
2 Department of Dermatology, University Hospital Erlangen, Erlangen, Germany
3 Dermatology, University Hospital Zurich, Zurich, Switzerland
4 Department of Dermatology, University Hospital Mainz, Germany
5 Department of Dermatology, University Hospital Wuerzburg, Wuerzburg, Germany
6 Department of Dermatology, University Hospital Muenster, Muenster, Germany
7 Central Unit for Biostatistics, German Cancer Research Center, Heidelberg, Germany
8 Department of Dermatology, University Hospital Erlangen, Erlangen, Germany; Department of Dermatology, University Hospital Wuerzburg, Wuerzburg, Germany

* To whom correspondence should be addressed.
D. Schadendorf, E-mail: d.schadendorf{at}dkfz.de


  Abstract

Background: This randomized phase III trial was designed to demonstrate the superiority of autologous peptide-loaded dendritic cell (DC) vaccination over standard dacarbazine (DTIC) chemotherapy in stage IV melanoma patients.

Patients and methods: DTIC 850 mg/m2 intravenously was applied in 4-week intervals. DC vaccines loaded with MHC class I and II-restricted peptides were applied subcutaneously at 2-week intervals for the first five vaccinations and every 4 weeks thereafter. The primary study end point was objective response (OR); secondary end points were toxicity, overall (OS) and progression-free survival (PFS).

Results: At the time of the first interim analysis 55 patients had been enrolled into the DTIC and 53 into the DC-arm (ITT). OR was low (DTIC: 5.5%, DC: 3.8%), but not significantly different in the two arms. The Data Safety & Monitoring Board recommended closure of the study. Unscheduled subset analyses revealed that patients with normal serum LDH and/or stage M1a/b survived longer in both arms than those with elevated serum LDH and/or stage M1c. Only in the DC-arm did those patients with (i) an initial unimpaired general health status (Karnofsky = 100) or (ii) an HLA-A2+/HLA-B44- haplotype survive significantly longer than patients with a Karnofsky index <100 (P = 0.007 versus P = 0.057 in the DTIC-arm) or other HLA haplotypes (P = 0.04 versus P = 0.57 in DTIC-treated patients).

Conclusions: DC vaccination could not be demonstrated to be more effective than DTIC chemotherapy in stage IV melanoma patients. The observed association of overall performance status and HLA haplotype with overall survival for patients treated by DC vaccination should be tested in future trials employing DC vaccines.

Keywords: advanced melanoma; dentric cells; DTIC; first-line therapy; melanoma.
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