title: A first in man phase I trial of the oral immunomodulator, indoximod, combined with docetaxel in patients with metastatic solid tumors.
abstract: BACKGROUND
  Indoleamine 2,3-dioxygenase (IDO) is an enzyme that tumors use to create a state of immunosuppression. Indoximod is an IDO pathway inhibitor. Preclinical studies demonstrated that indoximod combined with chemotherapy was synergistic in a mouse model of breast cancer. A phase I 3+3 trial was designed to study the combination of docetaxel and indoximod.
  
  
  METHODS
  Docetaxel was administered at 60 mg/m2 intravenously every 3 weeks dose levels 1-4 and 75 mg/m2 for dose level 5. Indoximod was given at 300, 600, 1000, 2000, and 1200 mg PO twice daily continuously for levels 1-5, respectively. Serum drug levels were measured.
  
  
  RESULTS
  Twenty-seven patients were treated, with 22 evaluable for response. DLTs included grade 3 dehydration (level 1), hypotension(level 4), mucositis (level 4) and grade 5 enterocolitis (level 2). Dose level 5 is the recommended phase II dose. The most frequent adverse events were fatigue (58.6%), anemia (51.7%), hyperglycemia (48.3%), infection (44.8%), and nausea (41.4%). There were 4 partial responses (2 breast, 1 NSCLC, 1 thymic tumor). No drug-drug interactions were noted.
  
  
  CONCLUSIONS
  Docetaxel plus indoximod was well tolerated with no increase in expected toxicities or pharmacokinetic interactions. It was active in a pretreated population of patients with metastatic solid tumors.
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Hatem H
authors.initials: HH
authors.lastname: Soliman
authors.affiliation: University of South Florida, Tampa, FL.
authors.forename: Erica
authors.initials: E
authors.lastname: Jackson
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Tony
authors.initials: T
authors.lastname: Neuger
authors.affiliation: University of North Carolina/Lineberger Cancer Center, Chapel Hill, NC.
authors.forename: E Claire
authors.initials: EC
authors.lastname: Dees
authors.affiliation: Winship Cancer Institute of Emory University, Atlanta, GA.
authors.forename: R Donald
authors.initials: RD
authors.lastname: Harvey
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Hyo
authors.initials: H
authors.lastname: Han
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Roohi
authors.initials: R
authors.lastname: Ismail-Khan
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Susan
authors.initials: S
authors.lastname: Minton
authors.affiliation: NewLink Genetics Inc, Ames, IA.
authors.forename: Nicholas N
authors.initials: NN
authors.lastname: Vahanian
authors.affiliation: NewLink Genetics Inc, Ames, IA.
authors.forename: Charles
authors.initials: C
authors.lastname: Link
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sullivan
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Scott
authors.initials: S
authors.lastname: Antonia
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D005431:Florida; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014364:Tryptophan / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D007155:Immunologic Factors; D043823:Taxoids; D000077143:Docetaxel; D014364:Tryptophan; C525396:1-methyltryptophan