title: Phase I dose-escalation study evaluating safety, tolerability and pharmacokinetics of MEDI-573, a dual IGF-I/II neutralizing antibody, in Japanese patients with advanced solid tumours.
abstract: OBJECTIVE
  This Phase I, open-label, single-arm, dose-escalation study aimed to evaluate the safety and tolerability of the insulin-like growth factor (IGF-I/II) neutralizing antibody, MEDI-573, in Japanese patients with advanced solid tumours refractory to standard therapy or for which no standard therapy exists. The pharmacokinetics, pharmacodynamics and antitumour activity of MEDI-573 were also evaluated.
  
  
  METHODS
  Three cohorts of patients received MEDI-573 in escalating order: cohort 1, 5 mg/kg on Day 1, 8 and 15; cohort 2, 15 mg/kg on Day 1, 8 and 15; cohort 3, 45 mg/kg on Day 1, of 21-day cycles.
  
  
  RESULTS
  Ten patients who received at least one dose of MEDI-573 were evaluated. The median number of treatment cycles was 2.0 (range 1-6) and the median number of MEDI-573 doses received was 4.0 (range 1-17). The most commonly reported drug-related adverse events were fatigue (n = 2 patients), pyrexia (n = 2), diarrhoea (n = 2) and electrocardiogram QT prolongation (n = 2). No patients experienced a dose-limiting toxicity. Pharmacokinetics of MEDI-573 were linear with a dose-dependent increase. There were no complete or partial responses; four patients had an overall best response of stable disease.
  
  
  CONCLUSIONS
  MEDI-573 is well tolerated at the doses investigated.
authors.affiliation: Clinical Research Center, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-chou, Matsuyama City, Ehime Prefecture, 791-0280, Japan, higuchi@shikoku-cc.go.jp.
authors.forename: Haruo
authors.initials: H
authors.lastname: Iguchi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishina
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Nogami
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kozuki
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yamagiwa
authors.forename: Katsuro
authors.initials: K
authors.lastname: Yagawa
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D044466:Asian People; D000080908:Broadly Neutralizing Antibodies; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000276:immunology; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D000080908:Broadly Neutralizing Antibodies; C000601324:dusigitumab; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II