title: A phase I study assessing the safety and pharmacokinetics of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with gemcitabine and cisplatin in patients with solid tumors.
abstract: BACKGROUND
  The aim of the study was to determine the safety profile, pharmacokinetics and potential drug interactions of the angiogenesis inhibitor ABT-510 combined with gemcitabine-cisplatin chemotherapy in patients with solid tumors.
  
  
  METHODS
  Patients with advanced solid tumors received gemcitabine 1250 mg/m2 intravenously (i.v.) on days 1 and 8 and cisplatin 80 mg/m2 on day 1 of a 3-week cycle in combination with ABT-510. ABT-510 was administered subcutaneously twice daily at doses of 50 mg or 100 mg. Plasma samples for pharmacokinetics were obtained on days 1 (gemcitabine, cisplatin as single agents), 15 (ABT-510 as single agent) and 22 (gemcitabine, cisplatin and ABT-510 as combination).
  
  
  RESULTS
  Thirteen patients received ABT-510 as either 50 mg b.i.d. (seven patients) or 100 mg b.i.d. (six patients) in combination with gemcitabine-cisplatin. The most common reported adverse events reflected the known toxicity profile induced by gemcitabine-cisplatin without ABT-510. One episode of hemoptysis occurred in a patient with non-small-cell lung cancer (NSCLC) after 13 days of treatment. No clinically significant pharmacokinetic interactions between ABT-510, gemcitabine and platinum were observed. Three partial responses were observed in 12 evaluable patients (one head and neck cancer, one melanoma and one NSCLC).
  
  
  CONCLUSIONS
  Combining ABT-510 at doses of 50 mg and 100 mg with gemcitabine-cisplatin is feasible. Pharmacokinetic interactions were not observed and adding ABT-510 does not appear to increase toxicity.
authors.affiliation: Department of Medical Oncology, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands. j.a.gietema@int.umcg.nl
authors.forename: J A
authors.initials: JA
authors.lastname: Gietema
authors.forename: R
authors.initials: R
authors.lastname: Hoekstra
authors.forename: F Y F L
authors.initials: FY
authors.lastname: de Vos
authors.forename: D R A
authors.initials: DR
authors.lastname: Uges
authors.forename: A
authors.initials: A
authors.lastname: van der Gaast
authors.forename: H J M
authors.initials: HJ
authors.lastname: Groen
authors.forename: W J
authors.initials: WJ
authors.lastname: Loos
authors.forename: R A
authors.initials: RA
authors.lastname: Knight
authors.forename: R A
authors.initials: RA
authors.lastname: Carr
authors.forename: R A
authors.initials: RA
authors.lastname: Humerickhouse
authors.forename: F A L M
authors.initials: FA
authors.lastname: Eskens
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019700:Thrombospondin 1 / Q000737:chemistry / Q000494:pharmacology; D000093542:Gemcitabine
chemical_list: D020533:Angiogenesis Inhibitors; C500617:NAc-Sar-Gly-Val-(d-allo-Ile)-Thr-Nva-Ile-Arg-ProNEt; D009842:Oligopeptides; D019700:Thrombospondin 1; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine