TY - JOUR
T1 - Seeing the forest through the trees
T2 - A systematic review of the safety and efficacy of combination chemotherapies used in the treatment of metastatic colorectal cancer
AU - Bekaii-Saab, Tanios
AU - Wu, Christina
N1 - Funding Information:
Medical editorial assistance was provided by Melanie Vishnu, PhD, of Articulate Science and supported by Bristol-Myers Squibb.
PY - 2014/7
Y1 - 2014/7
N2 - Combinations of fluoropyrimidines with oxaliplatin or irinotecan plus a biologic agent are standard treatments for metastatic colorectal cancer (mCRC). Recent approvals of first-line cetuximab, second-line ziv-aflibercept, and regorafenib as salvage therapy have increased the complexity of the treatment armamentarium. To define optimal regimens, we systematically reviewed combination chemotherapy trials (N= 83). Descriptive analyses focusing on fluoropyrimidine formulation, oxaliplatin vs irinotecan combinations, and compatibility with biologics indicated the following: infusional 5-fluorouracil (5-FU) yielded better efficacy and safety than bolus 5-FU. Capecitabine had similar outcomes and better safety than 5-FU with oxaliplatin but not irinotecan. First-line oxaliplatin and irinotecan appeared equivalent. Antiangiogenics, such as bevacizumab and ziv-aflibercept, and epidermal growth factor receptor-targeted monoclonal antibodies cetuximab and panitumumab further improved efficacy. The treatment landscape for mCRC has become complex, and we are approaching individualized therapy based on predictive factors, including KRAS mutational status. Appropriate administration of chemotherapy/biologic combinations is critical.
AB - Combinations of fluoropyrimidines with oxaliplatin or irinotecan plus a biologic agent are standard treatments for metastatic colorectal cancer (mCRC). Recent approvals of first-line cetuximab, second-line ziv-aflibercept, and regorafenib as salvage therapy have increased the complexity of the treatment armamentarium. To define optimal regimens, we systematically reviewed combination chemotherapy trials (N= 83). Descriptive analyses focusing on fluoropyrimidine formulation, oxaliplatin vs irinotecan combinations, and compatibility with biologics indicated the following: infusional 5-fluorouracil (5-FU) yielded better efficacy and safety than bolus 5-FU. Capecitabine had similar outcomes and better safety than 5-FU with oxaliplatin but not irinotecan. First-line oxaliplatin and irinotecan appeared equivalent. Antiangiogenics, such as bevacizumab and ziv-aflibercept, and epidermal growth factor receptor-targeted monoclonal antibodies cetuximab and panitumumab further improved efficacy. The treatment landscape for mCRC has become complex, and we are approaching individualized therapy based on predictive factors, including KRAS mutational status. Appropriate administration of chemotherapy/biologic combinations is critical.
KW - Bevacizumab
KW - Cetuximab
KW - Chemotherapy regimen sequencing
KW - FOLFIRI
KW - FOLFOX
KW - Irinotecan
KW - Metastatic colorectal cancer
KW - Oxaliplatin
UR - http://www.scopus.com/inward/record.url?scp=84901589715&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901589715&partnerID=8YFLogxK
U2 - 10.1016/j.critrevonc.2014.01.001
DO - 10.1016/j.critrevonc.2014.01.001
M3 - Review article
C2 - 24534706
AN - SCOPUS:84901589715
SN - 1040-8428
VL - 91
SP - 9
EP - 34
JO - Critical Reviews in Oncology/Hematology
JF - Critical Reviews in Oncology/Hematology
IS - 1
ER -