A prospective pilot study of target-guided personalized chemotherapy with intensity-modulated radiotherapy in patients with early rectal cancer

Antonio Cubillo, Ovidio Hernando-Requejo, Elena García-García, Jesús Rodriguez-Pascual, Emilio De Vicente, Pía Morelli, Carmen Rubio, Fernando López-Ríos, Avertano Muro, Ulpiano López, Susana Prados, Yolanda Quijano, Manuel Hidalgo

Research output: Contribution to journalArticle


Purpose: 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 2/12 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 wildtype 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.

Original languageEnglish (US)
Pages (from-to)117-121
Number of pages5
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Issue number2
Publication statusPublished - 2014
Externally publishedYes



  • Molecular targets
  • Personalized treatment
  • Rectal cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Medicine(all)

Cite this