J Cancer 2011; 2:81-89. doi:10.7150/jca.2.81

Research Paper

Phase I Dose Escalation Study of Sodium Stibogluconate (SSG), a Protein Tyrosine Phosphatase Inhibitor, Combined with Interferon Alpha for Patients with Solid Tumors

Aung Naing1✉, James M. Reuben2✉, Luis H. Camacho1, Hui Gao2, Bang-Ning Lee2, Evan N. Cohen2, Claire Verschraegen3, Saneese Stephen1, Joann Aaron1, David Hong1, Jennifer Wheler1, Razelle Kurzrock1

1. Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston Texas, USA
2. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston Texas, USA
3. University of New Mexico Cancer Research and Treatment Center, Albuquerque, NM 87131-0001, USA

Abstract

Purpose: Sodium stibogluconate (SSG), a small molecule inhibitor of protein tyrosine phosphatases, combined with IFN-alpha-2b (IFN-α) inhibited solid tumor cell line growth in vitro. We conducted a phase I clinical trial with SSG plus IFN-α in advanced cancer patients to assess tolerance, maximum tolerated dose (MTD) and immune system effects.

Experimental Design: SSG was administered intravenously alone for five days of week 1, cycle 1 (21 days per cycle) and together with IFN-α 2b s (3 million units sc TIW) in week 2, and after a rest during week 3, on a 2-week on/1-week off cycle. SSG dose levels were 400, 600, 900, 1125, and 1350 mg/m2.

Results: Twenty-four patients were studied. Common toxicities included asymptomatic elevated serum lipase, thrombocytopenia, fatigue, fever, chills and anemia. The dose-limiting toxicities (DLT) were hypokalemia, thrombocytopenia, fatigue, pancreatitis and skin rash. The MTD was 900 mg/m2 SSG and IFN-α, 3 million units TIW. At this dose, patients had a significantly lower number of regulatory T cells (TR Cells) (p = 0.012), myeloid dendritic cells (mDC) (p = 0.028); higher percentage of natural killer (NK) cells that synthesized perforin (p = 0.046) and of plasmacytoid dendritic cells (pDC) that secreted IFN-α (p = 0.018) in response to activation through toll-like receptor (TLR) 7 and TLR 8 by CL097, the highly water-soluble derivative of the imidazoquinoline compound R848.

Conclusions: SSG in combination with IFN-α 2b was well tolerated and augmented cellular immune parameters.

Keywords: sodium stibogluconate, phase 1, interferon alpha, immunity, cancer

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How to cite this article:
Naing A, Reuben JM, Camacho LH, Gao H, Lee BN, Cohen EN, Verschraegen C, Stephen S, Aaron J, Hong D, Wheler J, Kurzrock R. Phase I Dose Escalation Study of Sodium Stibogluconate (SSG), a Protein Tyrosine Phosphatase Inhibitor, Combined with Interferon Alpha for Patients with Solid Tumors. J Cancer 2011; 2:81-89. doi:10.7150/jca.2.81. Available from http://www.jcancer.org/v02p0081.htm