SO13P META‐ANALYSIS OF IRINOTECAN MOLECULAR TARGETED SECOND LINE CHEMOTHERAPY IN ADVANCED COLORECTAL CANCER

Abstract

In 2001, the lifetime risk of developing colorectal cancer (CRC) in Australia was 1 in 17 men and 1 in 26 women. Most patients with CRC undergo surgical resection and then commence adjuvant chemotherapy, except for stage A and some stage B cancers which avoid chemotherapy. Of the 46% of patients that develop recurrent or metastatic CRC, Oxaliplatin and 5‐Fluorouracil combined are the most extensively used first line treatment, with a response in 50–55% of patients. If the cancer progresses, Irinotecan is commenced, with 12–17.1% of patients responding. The aim of this review is to identify advanced CRC molecular markers that predict response to irinotecan in order to recommend treatment options for patients and to reduce morbidity. OvidSP, Proquest, Science Direct, PubMed, the ABS and the NHMRC were searched for literature between 1980 and 2009 on the treatment of advanced CRC with Irinotecan with specific focus on p53, VEGF and á‐B‐crystallin. Results: Phase II and III clinical trials conclude irinotecan improves pain free survival (p = 0.003), quality of life, one year survival, progression free survival (p = 0.030) and overall survival (p = 0.0001) in metastatic CRC. Irinotecan sensitizes p53 wild type, mutant and null cells to Fas‐mediated cell apoptosis in CRC cells (p < 0.001). Wild type p53 cells were more sensitive to irinotecan than mutated p53 (log rank test p = 0.05, p = 0.0004 respectively). Irinotecan has an anti‐VEGF effect inhibiting endothelial cell proliferation, increasing apoptosis and reducing microvascular density which is only limited by the irinotecan toxicity levels. There is currently no information correlating á‐B‐crystallin in CRC and irinotecan.