title: Role of conventional chemosensitivity test and tissue biomarker expression in predicting response to treatment of peritoneal carcinomatosis from colon cancer.
abstract: Peritoneal carcinomatosis (PC) is observed in approximately 10% of patients with colorectal cancer at the time of primary cancer resection. Most of these patients receive 5-fluorouracil (5-FU)- or oxaliplatin-containing chemotherapy regimens as first-, second-, or third-line treatment. In the present study, sensitivity and resistance to drugs used to treat PC were better defined by a conventional chemosensitivity test than by biomarker expression.
  
  
  BACKGROUND
  5-Fluorouracil- or oxaliplatin-based regimens are the treatments of choice in patients with PC from colon cancer. There are currently no useful preclinical evaluations to guide the decision-making process for tailored therapy. The aim of the present study was to compare the advantages and limits of a conventional in vitro chemosensitivity test with those of a panel of biomolecular markers in predicting clinical response to different drugs used to treat colon cancer-derived PC.
  
  
  METHODS
  Fresh surgical biopsy specimens were obtained from 28 patients with peritoneal carcinomatosis from colon cancer. TS, TP, DPD, MDR1, MRP-1, MGMT, BRCA1, ERCC1, GSTP1, and XPD gene expression levels were determined by real-time reverse transcription polymerase chain reaction. An in vitro chemosensitivity test was used to define a sensitivity or resistance profile to the drugs used to treat each patient.
  
  
  RESULTS
  Expression levels of the genes analyzed were generally poorly related to each other. TS and ERCC1 expression was inversely related to response to 5-FU-and/or oxaliplatin-containing regimens. Significant predictivity in terms of sensitivity but poor predictivity of resistance (56.2%) (P=.037) were observed for ERCC1 expression (90%), and high predictivity of resistance (100%) but very low predictivity of sensitivity (40%) (P=.014) were registered for TS. The best overall and significant predictivity was observed for chemosensitivity test results (62.5% sensitivity and 89% resistance; P=.005).
  
  
  CONCLUSIONS
  Sensitivity and resistance to drugs used in vivo was better defined by the chemosensitivity test than by biomarker expression.
authors: Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Italy.
authors: Chiara
authors: C
authors: Arienti
authors: Anna
authors: A
authors: Tesei
authors: Giorgio Maria
authors: GM
authors: Verdecchia
authors: Massimo
authors: M
authors: Framarini
authors: Salvatore
authors: S
authors: Virzì
authors: Antonio
authors: A
authors: Grassi
authors: Emanuela
authors: E
authors: Scarpi
authors: Livia
authors: L
authors: Turci
authors: Rosella
authors: R
authors: Silvestrini
authors: Dino
authors: D
authors: Amadori
authors: Wainer
authors: W
authors: Zoli
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics; D003110:Colonic Neoplasms / Q000473:pathology*; D003657:Decision Making; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil