title: Phase I Dose Escalation Study of Sodium Stibogluconate (SSG), a Protein Tyrosine Phosphatase Inhibitor, Combined with Interferon Alpha for Patients with Solid Tumors.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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/m(2).
  
  
  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/m(2 )SSG and IFN-α, 3 million units TIW. At this dose, patients had a significantly lower number of regulatory T cells (T(R )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.
authors.affiliation: 1. Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston Texas, USA.
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.forename: James M
authors.initials: JM
authors.lastname: Reuben
authors.forename: Luis H
authors.initials: LH
authors.lastname: Camacho
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.forename: Bang-Ning
authors.initials: BN
authors.lastname: Lee
authors.forename: Evan N
authors.initials: EN
authors.lastname: Cohen
authors.forename: Claire
authors.initials: C
authors.lastname: Verschraegen
authors.forename: Saneese
authors.initials: S
authors.lastname: Stephen
authors.forename: Joann
authors.initials: J
authors.lastname: Aaron
authors.forename: David
authors.initials: D
authors.lastname: Hong
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wheler
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock