title: Phase I dose-escalating study of TAS-106 in combination with carboplatin in patients with solid tumors.
abstract: BACKGROUND
  TAS-106 was designed to inhibit RNA synthesis by blocking RNA polymerases I, II, and III.
  
  
  METHODS
  This was a single-center, open-label, phase I study to identify the maximum tolerated dose (MTD), pharmacokinetics, and biologic effects of the combination of TAS-106 and carboplatin, following a standard 3 + 3 design. This phase I trial was comprised of a regimen of a 60-min IV infusion of carboplatin on day 1 of each 21-day cycle followed by a 24-h infusion of TAS-106, also on day 1 of each cycle.
  
  
  RESULTS
  39 patients were treated (21 male, 18 female, median age 62 years, range 21-80 years). Median number of prior therapies was 4. Maximum Tolerated Dose (MTD) was 3 mg/m(2) TAS-106 with AU 4 carboplatin. Dose-limiting toxicities were neutropenia and thrombocytopenia, with and without growth factor support. While no patients achieved a complete or partial response, four patients had stable disease lasting ≥4 months, including one patient each with ovarian, non-small cell lung, basal cell and colorectal cancer.
  
  
  CONCLUSIONS
  In summary, the combination of TAS-106 and carboplatin was well-tolerated, and further studies in non-small cell lung and ovarian cancer are warranted to assess the efficacy of this drug combination.
authors.affiliation: Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, 1400 Holcombe Boulevard, Houston, TX, 77030, USA, anaing@mdanderson.org.
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: Ralph G
authors.initials: RG
authors.lastname: Zinner
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Wheler
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Arakawa
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Falchook
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003562:Cytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003710:Demography; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009420:Nervous System / Q000473:pathology; D055815:Young Adult
chemical_list: C103084:1-(3-C-ethynylribopentofuranosyl)cytosine; D003562:Cytidine; D016190:Carboplatin