%0 Journal Article
%T Safety and Efficacy of 188-Rhenium-Labeled Antibody to Melanin in Patients with Metastatic Melanoma
%A M. Klein
%A M. Lotem
%A T. Peretz
%A S. T. Zwas
%A S. Mizrachi
%A Y. Liberman
%A R. Chisin
%A J. Schachter
%A I. G. Ron
%A G. Iosilevsky
%A J. A. Kennedy
%A E. Revskaya
%A A. W. de Kater
%A E. Banaga
%A V. Klutzaritz
%A N. Friedmann
%A E. Galun
%A G. L. DeNardo
%A S. J. DeNardo
%A A. Casadevall
%A E. Dadachova
%A G. B. Thornton
%J Journal of Skin Cancer
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/828329
%X There is a need for effective ¡°broad spectrum¡± therapies for metastatic melanoma which would be suitable for all patients. The objectives of Phase Ia/Ib studies were to evaluate the safety, pharmacokinetics, dosimetry, and antitumor activity of 188Re-6D2, a 188-Rhenium-labeled antibody to melanin. Stage IIIC/IV metastatic melanoma (MM) patients who failed standard therapies were enrolled in both studies. In Phase Ia, 10£¿mCi 188Re-6D2 were given while unlabeled antibody preload was escalated. In Phase Ib, the dose of 188Re-6D2 was escalated to 54£¿mCi. SPECT/CT revealed 188Re-6D2 uptake in melanoma metastases. The mean effective half-life of 188Re-6D2 was 12.4£¿h. Transient HAMA was observed in 9 patients. Six patients met the RECIST criteria for stable disease at 6 weeks. Two patients had durable disease stabilization for 14 weeks and one for 22 weeks. Median overall survival was 13 months with no dose-limiting toxicities. The data demonstrate that 188Re-6D2 was well tolerated, localized in melanoma metastases, and had antitumor activity, thus warranting its further investigation in patients with metastatic melanoma. 1. Introduction The incidence of melanoma is increasing worldwide, with a concomitant rise in mortality from metastatic disease. Patients who progress to stage IV metastatic melanoma (MM) have a median survival of less than 1 year [1]. In the United States, about 9,180 people will die from melanoma in 2012 (American Cancer Society, 2012). Until recently, treatment options for patients with stage IV disease were limited and offered marginal, if any, improvement in overall survival. This situation changed with the newly approved by FDA ipilimumab (anti-CTLA4 monoclonal antibody), an immunomodulator which in a phase III trial was shown to improve overall survival [2]. In addition, vemurafenib that inhibits mutated B-RAF protein offers hope for 40¨C60% melanoma patients carrying this mutation [3, 4]. However, the responses to the latter have been relatively short lasting followed by recurrences. In our search for alternative therapeutic options for MM we turned to radioimmunotherapy (RIT). RIT takes advantage of the specificity of the antigen-antibody interaction to deliver cytotoxic radiation to tumors [5, 6]. The clinical success of FDA-approved drugs such as ibritumomab tiuxetan (anti-CD20 monoclonal antibody (mAb) labeled with 90Yttrium) for treatment of primary, relapsed or refractory B-cell non-Hodgkin lymphoma demonstrates RIT potential as antineoplastic strategy. Unlike other therapies, RIT does not rely on specific genotypes, biochemical
%U http://www.hindawi.com/journals/jsc/2013/828329/