title: A phase I study evaluating cixutumumab, a type 1 insulin-like growth factor receptor inhibitor, given every 2 or 3 weeks in Japanese patients with advanced solid tumors.
abstract: The primary objective of this phase I trial was to establish the safety profile and pharmacokinetics of cixutumumab administered every 2 weeks (q2w) or every 3 weeks (q3w) in Japanese patients with advanced solid tumors. Exploratory analyses included preliminary antitumor activity.
  
  
  
  Patients received intravenous cixutumumab q2w or q3w (6-week cycle) in a standard 3 + 3 study design. Safety was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Patients received treatment until evidence of progressive disease or other withdrawal criteria were met. Pharmacokinetics were described using noncompartmental analyses. Antitumor activity was evaluated using Response Evaluation Criteria in Solid Tumors v1.0.
  
  
  
  A total of 21 patients were treated in one of four cohorts: 6 mg/kg q2w (n = 4); 10 mg/kg q2w (n = 7); 15 mg/kg q3w (n = 3); or 20 mg/kg q3w (n = 7). No patients experienced dose-limiting toxicity. A majority of patients (61.9 %) experienced one or more drug-related adverse event (AE). Related AEs included impaired glucose tolerance (n = 6 [28.6 %]) and diarrhea, nausea, stomatitis, fatigue, weight decrease, anorexia, rash, and hypertension (n = 2 each [9.5 %]). A best overall response of stable disease was seen in seven patients (33.3 %). The median duration of stable disease was 6.9 months (range 2.8, 6.9) for all cohorts. Although limited, pharmacokinetic results were as expected and were comparable between Japanese and Caucasian patients.
  
  
  
  Cixutumumab was generally well tolerated with no new safety concerns.
  
  
  
  NCT01007032.
authors.affiliation: Department Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan. tdoi@east.ncc.go.jp.|National Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa-shi, Chiba, 277-8577, Japan. tdoi@east.ncc.go.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Doi
authors.affiliation: Department Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Shitara
authors.affiliation: Department Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Department Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshino
authors.affiliation: Eli Lilly and Company, 440 Route 22 East, Bridgewater, NJ, 08807, USA.|PharmaPro Consulting, Inc, New York, NY, USA.
authors.forename: Aruna
authors.initials: A
authors.lastname: Dontabhaktuni
authors.affiliation: Eli Lilly and Company, 440 Route 22 East, Bridgewater, NJ, 08807, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Rebscher
authors.affiliation: Eli Lilly and Company, 440 Route 22 East, Bridgewater, NJ, 08807, USA.
authors.forename: Shande
authors.initials: S
authors.lastname: Tang
authors.affiliation: Eli Lilly and Company, 440 Route 22 East, Bridgewater, NJ, 08807, USA.|Sotio, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Cosaert
authors.affiliation: Department Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D066066:Response Evaluation Criteria in Solid Tumors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C557414:cixutumumab; D017526:Receptor, IGF Type 1
keywords: Cixutumumab; Insulin receptor; Japanese; Solid tumor