title: FOLFIRI and sunitinib as first-line treatment in metastatic colorectal cancer patients with liver metastases--a CESAR phase II study including pharmacokinetic, biomarker, and imaging data.
abstract: BACKGROUND
  The aim of this study was the evaluation of pharmacokinetic parameters, biomarkers, clinical outcome, and imaging parameters in metastatic colorectal cancer (mCRC) patients treated with FOLFIRI plus sunitinib.
  
  
  METHODS
  mCRC patients with liver metastases were treated with FOLFIRI and sunitinib as 1st line therapy. At protocol-defined time points, multicontrast magnetic resonance imaging (MRI)measurements, computed tomography (CT) scans, pharmacokinetics (PK), and biomarker analyses were performed during the first and second treatment cycle. Thereafter, patients were treated until tumor progression, investigatorâs decision due to toxicity, or patient withdrawal.
  
  
  RESULTS
  28 patients were screened, 26 were included, and 23 received at least one study medication. Full safety analysis was performed in 23 patients. Full PK and biomarker analyses were performed in 21 patients. Strong responses in tumor size reduction forced a change from the original imaging timing scheme. This unforeseen change in the timing scheme resulted in subgroups too small for meaningful statistical analysis of most imaging parameters. Thus, only a descriptive analysis of the MRI data was possible. In 21/22 patients, MRI showeda decrease of the liver metastases. Best response was partial remission (PR) in 8/17 patients. Plasma concentrations of sVEGFR-2 and sVEGFR-3 decreased in all patients. The majority of the patients developed some kind of toxicity not always deducible to FOLFIRI or sunitinib.
  
  
  CONCLUSIONS
  Due to the observed side effect profile, FOLFIRI plus sunitinib 37.5 mg per day cannot be recommended for previously untreated mCRC.
authors.forename: Klaus
authors.initials: K
authors.lastname: Mross
authors.forename: Max
authors.initials: M
authors.lastname: Scheulen
authors.forename: Dirk
authors.initials: D
authors.lastname: Strumberg
authors.forename: Jan
authors.initials: J
authors.lastname: Kuhlmann
authors.forename: Friederike
authors.initials: F
authors.lastname: Kanefendt
authors.forename: Fritz
authors.initials: F
authors.lastname: Sörgel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaehde
authors.forename: Iris
authors.initials: I
authors.lastname: Burkholder
authors.forename: Berta
authors.initials: B
authors.lastname: Moritz
authors.forename: Martin
authors.initials: M
authors.lastname: Büchert
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005472:Fluorouracil / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D002955:Leucovorin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008279:Magnetic Resonance Imaging / Q000379:methods; D011758:Pyrroles / Q000008:administration & dosage; D000077210:Sunitinib; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3; D002955:Leucovorin; D005472:Fluorouracil; D000077210:Sunitinib; D002166:Camptothecin