title: The safety and tolerability of intravenous ASA404 when administered in combination with docetaxel (60 or 75 mg/m²) in Japanese patients with advanced or recurrent solid tumors.
abstract: OBJECTIVE
  This Phase I study was carried out to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of the flavonoid tumor-vascular disrupting agent ASA404 (vadimezan) in combination with docetaxel in Japanese patients with advanced or recurrent solid tumors.
  
  
  METHODS
  Nine Japanese patients were given ASA404 (1800 mg/m(2)) plus two doses of docetaxel, 60 or 75 mg/m(2), administered every 3 weeks.
  
  
  RESULTS
  Dose-limiting toxicity of Grade 3 febrile neutropenia was observed in one patient during Cycle 1 at Level 2 of ASA404 (1800 mg/m(2)) and docetaxel (75 mg/m(2)) treatment. The most frequently reported adverse events were neutropenia, fatigue, alopecia, decreased appetite, constipation and injection site pain. These adverse events were mainly Grade 1 or 2 in severity and, with the exception of injection site pain, were typically associated with docetaxel therapy. A partial response was observed in one patient, and five patients (55.6%) exhibited stable disease. Overall, the study demonstrated that ASA404 has an acceptable tolerability profile when combined with docetaxel at doses up to 75 mg/m(2) in Japanese patients with advanced solid tumors.
  
  
  CONCLUSIONS
  The study supports the enrollment of Japanese patients in the Phase III study (ATTRACT-2) of ASA404 in combination with docetaxel for the second-line treatment of advanced non-small cell lung cancer. Clinicaltrials.gov identifier: NCT01285453.
authors.affiliation: Osaka City General Hospital, 2-13-22 Miyakojimahondori, Miyakojima-ku, Osaka 534-0021, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Daga
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.forename: Shizu
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Shimizu
authors.forename: Shinya
authors.initials: S
authors.lastname: Tokunaga
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Horio
authors.forename: Ken
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
mesh_terms: D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001066:Appetite / Q000187:drug effects; D044466:Asian People; D003248:Constipation / Q000139:chemically induced; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000209:etiology; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced*; D012720:Severity of Illness Index; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D044004:Xanthones / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D020533:Angiogenesis Inhibitors; D043823:Taxoids; D044004:Xanthones; C066668:vadimezan; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel