Predictive biomarkers with potential of converting conventional chemotherapy to targeted therapy in patients with metastatic colorectal cancer

TY - JOUR

T1 - Predictive biomarkers with potential of converting conventional chemotherapy to targeted therapy in patients with metastatic colorectal cancer

AU - Jensen, Niels Frank

AU - Smith, David Hersi

AU - Nygård, Sune Boris

AU - Rømer, Maria Unni Koefoed

AU - Nielsen, Kirsten Vang

AU - Brunner, Nils

PY - 2012/3

Y1 - 2012/3

N2 - The availability of systemic chemotherapy regimens for the treatment of patients with metastatic colorectal cancer (mCRC) is based on the results from large prospective, randomized studies. The main chemotherapeutic drugs used in treatment of mCRC are the fluoropyrimidines (5-fluorouracil (5-FU); capecitabine) in combination with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI). The objective response rate to either combination is approximately 50%, where no significant differences with regard to progression free survival or overall survival have been observed. Interestingly, a number of preclinical and clinical studies have indicated lack of full cross resistance between oxaliplatin based and irinotecan based treatment. Therefore, it is possible that certain mCRC patient subpopulations would benefit more from one drug combination rather than the other. To address this clinical problem there has been much focus on development and validation of predictive biomarkers for these three drugs. Here, we present a thorough review on the current status of predictive biomarkers for 5-FU, oxaliplatin and irinotecan treatment of mCRC patients. The overall conclusions were as follows: Several promising biomarker candidates were identified, notably thymidylate synthase for 5-FU, topoisomerase I for irinotecan and ERCC1 for oxaliplatin. However, these candidates warrant further analysis, where assay performance and clinical trial design should be in focus.

AB - The availability of systemic chemotherapy regimens for the treatment of patients with metastatic colorectal cancer (mCRC) is based on the results from large prospective, randomized studies. The main chemotherapeutic drugs used in treatment of mCRC are the fluoropyrimidines (5-fluorouracil (5-FU); capecitabine) in combination with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI). The objective response rate to either combination is approximately 50%, where no significant differences with regard to progression free survival or overall survival have been observed. Interestingly, a number of preclinical and clinical studies have indicated lack of full cross resistance between oxaliplatin based and irinotecan based treatment. Therefore, it is possible that certain mCRC patient subpopulations would benefit more from one drug combination rather than the other. To address this clinical problem there has been much focus on development and validation of predictive biomarkers for these three drugs. Here, we present a thorough review on the current status of predictive biomarkers for 5-FU, oxaliplatin and irinotecan treatment of mCRC patients. The overall conclusions were as follows: Several promising biomarker candidates were identified, notably thymidylate synthase for 5-FU, topoisomerase I for irinotecan and ERCC1 for oxaliplatin. However, these candidates warrant further analysis, where assay performance and clinical trial design should be in focus.

KW - Former LIFE faculty

KW - 5-fluorouracil

KW - irinotecan

KW - metastatic colorectal cancer

KW - oxaliplatin

KW - predictive biomarkers

U2 - 10.3109/00365521.2012.640835

DO - 10.3109/00365521.2012.640835

M3 - Journal article

C2 - 22181013

SN - 0036-5521

VL - 47

SP - 340

EP - 355

JO - Scandinavian Journal of Gastroenterology

JF - Scandinavian Journal of Gastroenterology

IS - 3

ER -