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

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 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.