title: Chronomodulated chemotherapy in metastatic gastrointestinal cancer combining 5-FU and sodium folinate with oxaliplatin, irinotecan or gemcitabine: the Jena experience in 79 patients.
abstract: OBJECTIVE
  To study efficacy and tolerability of chronomodulated (CM)-chemotherapy in patients with metastatic or locally advanced tumors of the GI tract. Furthermore, calcium folinate was replaced by sodium folinate due to better feasibility.
  
  
  METHODS
  We treated 79 patients with metastatic or locally advanced colorectal cancer ( n=52), cancer of the pancreas/biliary tract ( n=14), and other malignancies ( n=14) with a total of 592 courses of CM-therapy. Out of the total study population 53/79, i.e., 67.1% had received prior chemotherapy. Most of the patients (77.2%) received sodium-folinate-5-FU-oxaliplatin-CM (SOFOX-CM) as first-line chronomodulated therapy, 20.3% received sodium-folinate-5-FU-irinotecan-CM (SOFIRI-CM), and 2.5% ( n=1) received sodium-folinate-5-FU-gemcitabine-CM (SOFGEM-CM).
  
  
  RESULTS
  We found a moderate overall toxicity with grade 3-4 neuropathy in 7.46% of patients during a total of 433 courses of SOFOX-CM and grade 3-4 diarrhea in 10.26% of patients after 154 courses of SOFIRI-CM. SOFOX-CM had to be stopped only in one patient due to grade 3-4 sensory neuropathy. CM-therapy led to complete response (CR) in 1.3%, partial response (PR) in 15.2%, stable disease (SD) in 32.9%, and progressive disease (PD) in 44.3% of all patients. For the 26 chemonaive patients remission data were as follows: CR one patient (3.8%), PR four patients (15.4%), SD seven patients (26.9%), PD 12 patients (46.3%), lost to follow-up one patient (3.8%), and too-early-for-analysis one patient (3.8%). The median progression-free-survival (PFS) was 4 months (range, 0-24 months). The median PFS was also 4 months (range, 0-21 months) for those patients receiving SOFOX-CM as first CM-therapy ( n=61), while it was found to be 0 months (range, 0-10 months) for patients ( n=16) receiving SOFIRI-CM as first chronomodulated therapy.
  
  
  CONCLUSIONS
  We found CM-therapy to be effective and safe in the treatment of advanced malignancies of the GI tract. Sodium folinate offers superior feasibility and compatibility with cytostatic drugs without drawbacks.
authors.affiliation: Department of Internal Medicine II, Friedrich-Schiller University, Erlanger Allee 101, 07740 Jena, Germany. kay-oliver.kliche@med.uni-jena.de
authors.forename: Kay-Oliver
authors.initials: KO
authors.lastname: Kliche
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kubsch
authors.forename: Martin
authors.initials: M
authors.lastname: Raida
authors.forename: Rami
authors.initials: R
authors.lastname: Masri-Zada
authors.forename: Klaus
authors.initials: K
authors.lastname: Höffken
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005492:Folic Acid / Q000008:administration & dosage; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D013274:Stomach Neoplasms / Q000188:drug therapy; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000077146:Irinotecan; D005492:Folic Acid; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine