title: Gemcitabine and capecitabine for heavily pre-treated metastatic colorectal cancer patients--a phase II and translational research study.
abstract: OBJECTIVE
  We investigated the efficacy and safety of capecitabine and gemcitabin (GemCap) in heavily pre-treated, therapy-resistant metastatic colorectal cancer (mCRC) patients and the clinical importance of cell-free DNA (cfDNA) measurement.
  
  
  METHODS
  Patients' inclusion criteria included histopathologically-verified mCRC refractory to standard chemotherapy, adequate organ function and performance status. Treatment included capecitabine (2,000 mg/m(2) day on days 1-7 q2w) and gemcitabine (1,000 mg/m(2) on day 1). The number of DNA alleles was measured in pre-treatment plasma samples using an in-house developed qPCR.
  
  
  RESULTS
  Forty-nine patients were included in the study. GemCap was well-tolerated in the majority of patients. Disease control rate was 30%, median progression-free survival (PFS) and overall survival (OS) by intention-to-treat were 2.7 (95%CI=2.6-2.8) and 6.8 (95%CI=5.0-7.7) months. Median OS in patients with cfDNA concentrations above the median (13,200 alleles/ml) was 4.7 (3.7-9.6) months compared to 7.8 months in the remaining patients (HR=2.22; 1.07-3.9; p=0.0186). The prognostic value of the cell-free DNA (cfDNA) was confirmed by multivariate analysis.
  
  
  CONCLUSIONS
  GemCap was well-tolerated with encouraging efficacy, and cfDNA was shown to hold a strong prognostic value.
authors: Department of Oncology, Aarhus University Hospital, Norrebrogade 44, 8000 Aarhus C, Denmark. k.g.spindler@rm.dk.
authors: Karen-Lise G
authors: KL
authors: Spindler
authors: Niels
authors: N
authors: Pallisgaard
authors: Rikke F
authors: RF
authors: Andersen
authors: John
authors: J
authors: Ploen
authors: Anders
authors: A
authors: Jakobsen
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D057170:Translational Research, Biomedical; D000093542:Gemcitabine
chemical_list: D004273:DNA, Neoplasm; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine
keywords: GemCap; cell-free DNA; metastatic colorectal cancer; plasma