title: Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  The insulin-like growth factor (IGF) signaling pathway has been implicated in the pathogenesis of numerous tumor types, including non-small cell lung cancer (NSCLC). Figitumumab is a fully human IgG2 monoclonal antibody against IGF-1 receptor (IGF-1R).
  
  
  METHODS
  This phase I, open-label, dose-escalation study (ClinicalTrials.gov: NCT00603538) assessed the safety and tolerability of figitumumab (6, 10 and 20 mg/kg) in combination with carboplatin (area under the curve: 6 mg·min/mL) and paclitaxel (200 mg/m(2)) in Japanese patients (N = 19) with chemotherapy-naïve, advanced NSCLC. Treatments were administered intravenously on day 1 of a 21-day cycle for four to six cycles. Pharmacokinetics, biomarkers, and antitumor activity were also evaluated.
  
  
  RESULTS
  Figitumumab in combination with carboplatin and paclitaxel was well tolerated at doses up to 20 mg/kg; no dose-limiting toxicities were observed at this dose level. When given in combination, figitumumab plasma exposure increased in an approximately dose-proportional manner. The approximate 2-fold accumulation following repeated administration supported the 21-day regimen as appropriate for figitumumab administration. Serum total IGF-1 and IGF binding protein-3 concentrations increased following figitumumab dosing, but a clear dose-dependent relationship was not demonstrated. Seven of 18 evaluable patients experienced a partial response.
  
  
  CONCLUSIONS
  Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC. Further analysis of biomarker data is necessary for the development of figitumumab therapy.
authors: Department of Internal Medicine, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors: Yasushi
authors: Y
authors: Goto
authors: Ikuo
authors: I
authors: Sekine
authors: Maki
authors: M
authors: Tanioka
authors: Takashi
authors: T
authors: Shibata
authors: Chiharu
authors: C
authors: Tanai
authors: Hajime
authors: H
authors: Asahina
authors: Hiroshi
authors: H
authors: Nokihara
authors: Noboru
authors: N
authors: Yamamoto
authors: Hideo
authors: H
authors: Kunitoh
authors: Yuichiro
authors: Y
authors: Ohe
authors: Hironori
authors: H
authors: Kikkawa
authors: Emiko
authors: E
authors: Ohki
authors: Tomohide
authors: T
authors: Tamura
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044466:Asian People; D014408:Biomarkers, Tumor / Q000097:blood; D016190:Carboplatin / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous; D007564:Japan; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016756:Immunoglobulins, Intravenous; D016190:Carboplatin; D017239:Paclitaxel; C525021:figitumumab