Pretreatment selection of regimen according to genetic analysis improves the efficacy of chemotherapy in the first line treatment of metastatic colorectal cancer

• Published in: Journal of surgical oncology 2014-03, Vol.109 (3), p.250-254
• Main Authors: Kim, Do Yoon, Paek, Tae Yoon, Oh, Seung Yeop, Kim, Young Bae, Lee, Je Hee, Lee, Mi Young, Choi, Zi Sun, Suh, Kwang Wook
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - genetics; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Colorectal Neoplasms - diagnostic imaging; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; DNA-Binding Proteins - genetics; Female; Fluorouracil - administration & dosage; Gene Expression Regulation, Neoplastic; genomic polymorphisms; Glucuronosyltransferase - genetics; Glutathione S-Transferase pi - genetics; Humans; Leucovorin - administration & dosage; Male; metastatic colon cancer; Middle Aged; Molecular Targeted Therapy - methods; Organoplatinum Compounds - administration & dosage; Polymorphism, Single Nucleotide; pretreatment genetic analysis; Republic of Korea; Survival Analysis; Tomography, X-Ray Computed; Treatment Outcome; X-ray Repair Cross Complementing Protein 1; Xeroderma Pigmentosum Group D Protein - genetics
• ISSN: 0022-4790; 1096-9098
• DOI: 10.1002/jso.23500

Background and Objectives Metastatic colon cancer patients are treated with the chemotherapy regimens, FOLFOX and FOLFIRI, in either order. So far, we cannot predict the response of chemotherapeutic agent, so it is necessary to find which regimen is adequate before starting chemotherapy. Methods Enrolled patients are randomized into either conventional treatment or planned treatment preceded by pretreatment genetic analysis. Blood samples of patients in planned treatment group (N = 53) were analyzed for the genetic polymorphism before selection of chemotherapeutic agents. Target genes were XPD‐751, GSTP‐1‐105, XRCC1‐399 for oxaliplatin, UGT1A1 for irinotecan. The response was measured by computed tomographic scan after completion of three cycles of chemotherapy. Results Overall response rate was significantly higher in planned group (67.9% vs. 46.3%, P = 0.020). In FOLFOX group, response rate was significantly improved in the planned patients(77.1% vs. 50%, P = 0.018). In FOLFIRI group, the difference didn't reach statistical significance (50% vs. 42.5%, P = 0.776). Conclusions We found significantly improved response rates in the chemotherapy of metastatic colon cancer by pretreatment genetic analysis, especially in FOLFOX group. J. Surg. Oncol. 2014 109:250–254. © 2013 Wiley Periodicals, Inc.