Phase I Dose Escalation Study of Sodium Stibogluconate (SSG), a Protein Tyrosine Phosphatase Inhibitor, Combined with Interferon Alpha for Patients with Solid Tumors
| Autor: | Claire F. Verschraegen, David S. Hong, Bang Ning Lee, Jennifer J. Wheler, Evan N. Cohen, Razelle Kurzrock, James M. Reuben, Luis H. Camacho, Joann Aaron, Saneese Stephen, Aung Naing, Hui Gao |
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| Rok vydání: | 2011 |
| Předmět: |
Myeloid
Sodium stibogluconate Oncology and Carcinogenesis Phases of clinical research Alpha interferon Protein tyrosine phosphatase Pharmacology sodium stibogluconate Immune system Clinical Research medicine cancer interferon alpha Receptor business.industry Hematology immunity medicine.anatomical_structure phase 1 Oncology 6.1 Pharmaceuticals Immunology Chills medicine.symptom business Research Paper medicine.drug |
| Zdroj: | Journal of Cancer, vol 2, iss 1 Journal of Cancer |
| ISSN: | 1837-9664 |
| DOI: | 10.7150/jca.2.81 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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