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A Prospective Pilot Study of Target-guided Personalized Chemotherapy with Intensity-modulated Radiotherapy in Patients With Early Rectal Cancer

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

American Journal of Clinical Oncology: April 2014 - Volume 37 - Issue 2 - p 117–121
doi: 10.1097/COC.0b013e31826e0703
Original Articles: Gastrointestinal

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/m2/12 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.

*Centro Integral Oncológico Clara Campal

§Therapeutics Targets Laboratory

Department of Clinical Medicine, Universidad CEU San Pablo

Centro Nacional de Investigaciones Oncologicas, Madrid, Spain

The authors declare no conflicts of interest.

Reprints: Antonio Cubillo, MD, PhD, Centro Integral Oncológico Clara Campal (CIOCC), c Oña 10, Madrid 28050, Spain. E-mail:

© 2014 by Lippincott Williams & Wilkins, Inc