title: Phase II Trial of Target-guided Personalized Chemotherapy in First-line Metastatic Colorectal Cancer.
abstract: The aim of this study was to investigate the feasibility and efficacy of personalizing treatment of patients with advanced untreated colorectal cancer (CRC).
  
  
  
  Patients with untreated metastatic CRC, performance status 0-1, and candidates for systemic chemotherapy were eligible. Tumor tissues were analyzed for KRAS, BRAF, and PI3K mutations and expression of topoisomerase-1 (Topo-1), excision repair cross-complementing gene 1 (ERCC1), thymidylate synthase (TS), and thymidine phosphorylase (TP). Patients with Topo-1 expression received irinotecan, whereas patients with negative Topo-1 and ERCC1 expression received oxaliplatin. Otherwise, patients received physician's choice of treatment. If TS was positive, no fluoropyrimidine was administered and if negative, 5-flurorouracil if TP was negative, or capecitabine if TP was positive. KRAS-mutated patients were treated with bevacizumab, whereas KRAS-native received cetuximab. The primary endpoint of the study was progression-free survival (PFS).
  
  
  
  A total of 74 patients were enrolled and 67 received personalized treatment including irinotecan (n=27), oxaliplatin (n=16), FOLFIRI (n=12), and FOLFOX (n=12). Thirty-eight patients received cetuximab and 29 bevacizumab. With a median follow-up time of 18.3 months (95% confidence interval [CI], 4-36), the overall median PFS was 8.3 months (95% CI, 6.9-9.7), representing a 12-month PFS rate of 36.5% (95% CI, 25-48). Overall clinical benefit, including response rate and disease stabilization, was 86% (95% CI, 73%-97%). The overall median survival was 21 months (95% CI, 11-40).
  
  
  
  Real-time target-guided personalized first-line treatment of patients with advanced CRC is feasible but, with the approached used, did not result in a clear improvement in PFS to warrant phase III testing.
authors: *Centro Integral Oncológico Clara Campal ‡Therapeutics Targets Laboratory †Universidad CEU San Pablo §Centro Nacional de Investigaciones Oncologicas, Madrid, Spain.
authors: Antonio
authors: A
authors: Cubillo
authors: Jesús
authors: J
authors: Rodriguez-Pascual
authors: Fernando
authors: F
authors: López-Ríos
authors: Carlos
authors: C
authors: Plaza
authors: Elena
authors: E
authors: García
authors: Rafael
authors: R
authors: Álvarez
authors: Emilio
authors: E
authors: de Vicente
authors: Yolanda
authors: Y
authors: Quijano
authors: Ovidio
authors: O
authors: Hernando
authors: Carmen
authors: C
authors: Rubio
authors: Sofía
authors: S
authors: Perea
authors: Gema
authors: G
authors: Sanchez
authors: Manuel
authors: M
authors: Hidalgo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine / Q000008:administration & dosage; D000068818:Cetuximab / Q000008:administration & dosage; D000066491:Clinical Decision-Making; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis; D004264:DNA Topoisomerases, Type I / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D003663:Decision Trees; D018572:Disease-Free Survival; D004720:Endonucleases / Q000032:analysis; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics; D057285:Precision Medicine; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D066066:Response Evaluation Criteria in Solid Tumors; D013939:Thymidine Phosphorylase / Q000032:analysis; D013940:Thymidylate Synthase / Q000032:analysis
chemical_list: D004268:DNA-Binding Proteins; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000069287:Capecitabine; D000077146:Irinotecan; D013940:Thymidylate Synthase; D013939:Thymidine Phosphorylase; D058539:Phosphatidylinositol 3-Kinase; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C071447:ERCC1 protein, human; D004720:Endonucleases; D016283:Proto-Oncogene Proteins p21(ras); D004264:DNA Topoisomerases, Type I; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin