Irinotecan therapy and molecular targets in colorectal cancer: a systemic review.
Irinotecan is the second line chemotherapy for advanced stage colorectal cancer (CRC) after failure of first line chemotherapy with oxaliplatin and 5-fluorouracil. The aim of this review is to analyse the data on irinotecan as second line chemotherapy for advanced CRC and the potential roles of the molecular markers, p53 and vascular endothelial growth factor (VEGF) in the management of advanced CRC. Thus, the English literature from 1980 to 2008 concerning irinotecan, p53, VEGF and CRC was reviewed. On review, Phase II and III clinical trials showed that irinotecan improves pain-free survival, quality of life, 1-year survival, progression-free survival and overall survival in advanced CRC. p53 and VEGF were expressed in CRC and had a predictive power of aggressive clinical behaviour in CRC. Irinotecan sensitizes p53 wild type, mutant and null cells to Fas-mediated cell apoptosis in CRC cells. Wild type p53 cells were more sensitive to irinotecan than mutated p53. Irinotecan has an anti-VEGF effect inhibiting endothelial cell proliferation, increasing apoptosis and reducing microvascular density which is only limited by irinotecan toxicity levels. To conclude, irinotecan improves the patient's quality of life and the survival rates of patients with advanced CRC. p53 and VEGF status of the patients' tumour is likely to affect the responsiveness of CRC to irinotecan. It is recommended that studies of the expression of these molecular markers in relation to chemo-responsiveness of irinotecan should be carried out for better management of patients with advanced CRC.
Weekes
Jessica
J
Discipline of Surgery (School of Medicine) and North Queensland Centre for Cancer Research (Australian Institute of Tropical Medicine), James Cook University, Townsville, Queensland, Australia.
Lam
Alfred King-Yin
AK
Sebesan
Sabe
S
Ho
Yik-Hong
YH
D006801:Humans; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D000077146:Irinotecan; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D000077146:Irinotecan; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A