title: Phase I study of matuzumab in combination with 5-fluorouracil, leucovorin and cisplatin (PLF) in patients with advanced gastric and esophagogastric adenocarcinomas.
abstract: BACKGROUND
  To evaluate the safety and tolerability of two different weekly doses of the fully humanized epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab combined with high-dose 5-fluorouracil, leucovorin and cisplatin (PLF) in the first-line treatment of patients with EGFR-positive advanced gastric and esophagogastric adenocarcinomas.
  
  
  METHODS
  Patients were treated in two matuzumab dose groups with the first cohort of patients receiving 400 mg matuzumab in combination with PLF. Based on the safety observations the next cohort of patients received 800 mg matuzumab. The study was conducted in two parts, with phase A, designed to assess the safety and tolerability of the combination, and phase B designed to be a treatment continuation for those patients benefiting from treatment. Treatment cycles were 7 weeks each. Each patient received the dose of matuzumab they were assigned to at study entry for the duration of the study.
  
  
  RESULTS
  Fifteen EGFR-positive patients were enrolled into the two matuzumab dose groups; 400 mg dose n=7; 800 mg dose n=8. All patients experienced at least one adverse event (AE). No patient experienced any serious AE which was considered to be related to matuzumab. Two grade 3 AEs possibly related to matuzumab occurred in 2 different patients (13.3 %), both in the 800 mg dose group. No dose-limiting toxicity (DLT) was observed in the 400 mg group. The maximum tolerated dose of matuzumab was not reached. The best confirmed overall response rate was 26.7 %.
  
  
  CONCLUSIONS
  Matuzumab, in combination with PLF, demonstrated an acceptable safety profile with modest anti-tumor activity.
authors: Department of Medicine (Cancer Research), West German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany. tanja.trarbach@uk-essen.de
authors: Tanja
authors: T
authors: Trarbach
authors: Marta
authors: M
authors: Przyborek
authors: Norbert
authors: N
authors: Schleucher
authors: Steffen
authors: S
authors: Heeger
authors: Christian
authors: C
authors: Lüpfert
authors: Udo
authors: U
authors: Vanhoefer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D066246:ErbB Receptors / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; 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; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; C520777:matuzumab; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil