title: Phase I study of imatinib, cisplatin and 5-fluoruracil or capecitabine in advanced esophageal and gastric adenocarcinoma.
abstract: BACKGROUND
  Despite all benefit provided by established therapies prognosis of gastric cancer remains poor. Targeted inhibition of platelet derived growth factor receptor (PDGFR) by imatinib may influence tumor growth and amplify chemotherapeutic effects.
  
  
  METHODS
  This phase I study evaluated dose limiting toxicity (DLT) of imatinib combinated with chemotherapy according to a 3-patient cohort dose-escalating design. Thirty-five patients received cisplatin (60 mg/m(2) d1 q 3w)/ capecitabine (1250 mg/m(2) bid d1-14 q 21) or cisplatin (50 mg/m(2) d1 q 2w)/ 5-fluoruracil (2 g/m(2) d1, q 1w). Imatinib was started d - 4 with dose escalation from 300 to 700 mg QD in 100 mg steps.
  
  
  RESULTS
  At imatinib dose level 1 (300mg) one DLT was observed, three more patients were enrolled without further DLT. At dose level 5 (700 mg) two gastric perforations occurred, so 600 mg imatinib emerged as the maximum tolerated dose. Major grade 3/4 toxicities were nausea (6%), anemia (6%) and fatigue (3%). Response evaluation revealed partial response in 27% and stable disease in 43% of the assessable patients.
  
  
  CONCLUSIONS
  Combination of imatinib and chemotherapy is well tolerated. Response rates were not superior to those of standard therapy. Further investigations of a larger group of patients are required to confirm the amplification of chemotherapy effects by imatinib.
  
  
  BACKGROUND
  European Clinical Trials Database: Eudra-CT2006-005792-17 and Clinical Trials Database: NCT00601510.
authors.affiliation: Department of Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Mayr
authors.forename: Karen
authors.initials: K
authors.lastname: Becker
authors.forename: Nadine
authors.initials: N
authors.lastname: Schulte
authors.forename: Sebastian
authors.initials: S
authors.lastname: Belle
authors.forename: Ralf
authors.initials: R
authors.lastname: Hofheinz
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Krause
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Ebert
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D003841:Deoxycytidine; D000069287:Capecitabine; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor; D002945:Cisplatin; D005472:Fluorouracil