title: A prospective pilot study of target-guided personalized chemotherapy with intensity-modulated radiotherapy in patients with early rectal cancer.
abstract: OBJECTIVE
  To investigate the feasibility of personalizing chemotherapy in patients with rectal cancer.
  
  
  METHODS
  Patients with cT3 or cN1 and cM0 rectal cancer were eligible. A set of 6 molecular markers including KRAS, BRAF, and PI3K mutations and expression of topoisomerase-1 (Topo-1), ERCC-1, and thymidylate synthase (TS) using immunohistochemistry were performed in a tumor biopsy. All patients were treated with capecitabine 625 to 825 mg/m/12 h M-F in combination with either irinotecan or oxaliplatin based on Topo-1 and ERCC-1 expression plus either bevacizumab or cetuximab based on the mutation status. All patients received intensity-modulated radiation therapy. A surgery was performed 6 to 8 weeks after the treatment.
  
  
  RESULTS
  Fifteen patients (94%) had T3 tumor and 10 (62%) N+ disease of 16 patients enrolled. In all patients, the full set of markers was analyzed within 10 days. Seven patients had K-ras mutation, and 4, 5, and 10 expressed Topo-1, ERRC-1 and TS, respectively. All patients had wild-type BRAF and PI3K tumors. The median time from obtaining informed consent to the treatment period was 18 days and all patients completed the chemoradiation treatment. Fifty percent achieved a complete pathologic response to treatment. Four patients (25%) developed grade 3 proctitis or diarrhea. There were no relevant surgical complications. Sixty-nine percent of the patients received adjuvant XELOX.
  
  
  CONCLUSIONS
  The individualization of neoadjuvant chemotherapy in patients with rectal cancer is feasible and leads to a high rate of pathologic response.
authors.affiliation: *Centro Integral Oncológico Clara Campal §Therapeutics Targets Laboratory †Department of Clinical Medicine, Universidad CEU San Pablo ‡Centro Nacional de Investigaciones Oncologicas, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cubillo
authors.forename: Ovidio
authors.initials: O
authors.lastname: Hernando-Requejo
authors.forename: Elena
authors.initials: E
authors.lastname: García-García
authors.forename: Jesús
authors.initials: J
authors.lastname: Rodriguez-Pascual
authors.forename: Emilio
authors.initials: E
authors.lastname: De Vicente
authors.forename: Pía
authors.initials: P
authors.lastname: Morelli
authors.forename: Carmen
authors.initials: C
authors.lastname: Rubio
authors.forename: Fernando
authors.initials: F
authors.lastname: López-Ríos
authors.forename: Avertano
authors.initials: A
authors.lastname: Muro
authors.forename: Ulpiano
authors.initials: U
authors.lastname: López
authors.forename: Susana
authors.initials: S
authors.lastname: Prados
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Quijano
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D000068818:Cetuximab; D059248:Chemoradiotherapy; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010071:Oxaloacetates; D019869:Phosphatidylinositol 3-Kinases; D010865:Pilot Projects; D057285:Precision Medicine / Q000379:methods; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy* / Q000601:surgery; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002166:Camptothecin; D000069287:Capecitabine; D000068818:Cetuximab; D004264:DNA Topoisomerases, Type I; D003841:Deoxycytidine; D005472:Fluorouracil; D000077146:Irinotecan; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010071:Oxaloacetates; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; C117307:KRAS protein, human; C482119:BRAF protein, human; C528909:TOP1 protein, human