title: Safety and Pharmacokinetics of Second-line Ramucirumab plus FOLFIRI in Japanese Patients with Metastatic Colorectal Carcinoma.
abstract: BACKGROUND
  This phase Ib study evaluated the pharmacokinetic profile and safety of ramucirumab, a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor 2, in combination with irinotecan, levofolinate and 5-fluorouracil (FOLFIRI) in Japanese patients with metastatic colorectal carcinoma (mCRC).
  
  
  METHODS
  Eligible patients had Eastern Cooperative Oncology Group performance status 0-1, and disease progression during or within 6 months following first-line therapy with bevacizumab, oxaliplatin and a fluoropyrimidine. Six enrolled patients received 8 mg/kg ramucirumab plus FOLFIRI every 2 weeks.
  
  
  RESULTS
  One out of six patients experienced a dose-limiting toxicity (grade 2 proteinuria and grade 4 neutropenia, resulting in a dose delay >2 weeks). All patients experienced at least one grade 3 or higher adverse event: neutropenia (five patients, 83%), proteinuria (two patients; 33%) and anemia, thrombocytopenia and hypertension (one patient each, 17%). There were no serious adverse events or deaths.
  
  
  CONCLUSIONS
  Ramucirumab plus FOLFIRI was well-tolerated in Japanese patients with mCRC, warranting further investigation of this combination therapy.
authors.affiliation: National Cancer Center Hospital East, Kashiwa, Japan tyoshino@east.ncc.go.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshino
authors.affiliation: Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Osaka Medical College Hospital, Takatsuki, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Eli Lilly and Company, Bridgewater, NJ, U.S.A.
authors.forename: Federico
authors.initials: F
authors.lastname: Nasroulah
authors.affiliation: Eli Lilly and Company, Bridgewater, NJ, U.S.A.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.affiliation: Eli Lilly Japan K.K., Kobe, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Yoshizuka
authors.affiliation: National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D002166:Camptothecin; D005472:Fluorouracil; D002955:Leucovorin; D000096662:Ramucirumab
keywords: FOLFIRI; Japanese patients; Ramucirumab; metastatic colorectal carcinoma; pharmacokinetics