title: Chronomodulated chemotherapy with oxaliplatin, 5-FU and sodium folinate in metastatic gastrointestinal cancer patients: original analysis of non-hematological toxicity and patient characteristics in a pilot investigation.
abstract: OBJECTIVE
  Several clinical trials have demonstrated that oxaliplatin is a useful agent in combination with 5-fluorouracil (5-FU) and folinic acid (FA) for the treatment of patients with colorectal carcinoma. The aims of this pilot study were to evaluate non-hematological toxicity and patient characteristics in gastrointestinal cancer patients treated with chronomodulated chemotherapy consisting of oxaliplatin, 5-FU and sodium folinate.
  
  
  METHODS
  Patients with metastatic gastrointestinal cancer received a chronomodulated regimen with oxaliplatin (25 mg/m2), 5-FU (750 mg/m2) and sodium folinate (150 mg/m2). Non-hematological toxicities were evaluated and analyzed in relation to patient characteristics, i.e. age, sex, body weight, body mass index (BMI), body surface area and smoking status. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria.
  
  
  RESULTS
  The severity of non-hematological toxicity was generally moderate. Grade 4 toxicity was only found in 2 patients with diarrhea (12.5%). The most frequent common adverse events were nausea, Grades 1 - 2 in 13 patients (81.3%), followed by motor neuropathy, Grades 1 - 3 in 11 patients (68.9%). The analyses showed that patient characteristics such as BMI and smoking status were associated with mucositis/stomatitis, vomiting or mood alteration. Furthermore, there was a relationship between smoking status and the overall non-hematological toxicity. Smokers had significantly higher overall toxicity than non-smokers and body mass index correlated significant with overall toxicity.
  
  
  CONCLUSIONS
  The results of this pilot investigation suggest that a chronomodulated regimen with oxaliplatin, 5-FU and sodium folinate has a manageable non-hematological toxicity profile and that toxicity of the chronomodulated schedule studied depends on the patient characteristics. In further investigations, risk factors determining chemotherapeutic toxicity should be considered. Because of the small number of patients in this pilot investigation, the findings need to be confirmed in a larger clinical study.
authors.affiliation: Institute of Clinical Pharmacology, Friedrich Schiller University Jena, Dornburger Strasse 159, 07740 Jena, Germany. katrin.farker@med.uni-jena.de
authors.forename: K
authors.initials: K
authors.lastname: Farker
authors.forename: U
authors.initials: U
authors.lastname: Merkel
authors.forename: U
authors.initials: U
authors.lastname: Wedding
authors.forename: M
authors.initials: M
authors.lastname: Hippius
authors.forename: K
authors.initials: K
authors.lastname: Höffken
authors.forename: A
authors.initials: A
authors.lastname: Hoffmann
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015992:Body Mass Index; D019454:Chronotherapy / Q000379:methods*; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000187:drug effects; D052016:Mucositis / Q000139:chemically induced; D009325:Nausea / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D018579:Patient Selection; D010865:Pilot Projects; D012307:Risk Factors; D012720:Severity of Illness Index; D013280:Stomatitis / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil