P-189 - Correlation between of expression of the enzyme topoisomerase I and p53 and result of irinotecan based therapy in patients with metastatic colorecta...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Translational Research
Presenter A. Pasic
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors A. Pasic, S. Beslija, A. Djuran, I. Sefic-Pasic, M. Banjin, T. Ceric, A. Rasic, B. Hasanbegovic, A. Jalovcic, E. Kapisazovic
  • Clinical Center University of Sarajevo, Sarajevo/BA

Abstract

Introduction

Colorectal cancer is the second most common cause of death from malignancy in the Western world. Results of treatment in patients with metastatic disease are unsatisfactory. Combination therapy based on irinotecan has been first line therapy for mCRC since year 2000. Irinotecan is a topoisomerase I inhibitor. Given that less than half of patients have a good therapeutic response to treatment with irinotecan it is of great importance to determine the group of patients who will benefit most from this therapy. Aim of our study was to determine the significance of the expression of topoisomerase I and p53 as a predictive factors for treatment with irinotecan in patients with mCRC and to determine the correlation between the expression levels of topoisomerase I and the results of treatment with irinotecan and oxaliplatin, as measured by time to progression (TTP) and clinical benefit rate (CBR).

Methods

We analyzed histological material of 70 patients with mCRC who were treated and followed at the Institute of Oncology Sarajevo from 2002 to 2009. Immunohistochemistry analysis of the expression of the enzyme topoisomerase I and p53 was correlated with clinical outcomes of patients' treatment. Patients were divided into two groups: patients who receive treatment irinotecan-based therapy and patients who received oxaliplatin-based therapy.

Results

We did not find statistically significant difference in CBR and TTP between irinotecan and oxaliplatin group. CBR with irinotecan was 70% and with oxaliplatin 83.3% (p = 0.198). Also there was no significant difference in TTP (9.58 vs. 11.7 months, p = 0.109). For patients that had an overexpression of topoisomerase I, TTP was similar for irinotecan and oxaliplatin group (9.1 vs. 8.5 months, p = 0.692). However, patients who had overexpression of topoisomerase 1 responded worst compared to patient with no/weak topoisomerase I expression (8.9 vs. 11.7 months, p = 0.068). There were no significant differences in response to treatment with irinotecan in patients who have had the expression of topoisomerase I, in less than 30% or more than 30% of tumor cells (TTP 9.9 vs. 9.1 months). Topoisomerase I overexpression was found in 47.5% of patients. We did not find significant difference in TTP between patients who did or did not have an increased expression of P-53, p = 0.564. There was no significant difference in survival rate between for patients receiving irinotecan, regarding expression of p53, p = 0.383.

Conclusion

Overexpression of topoisomerase 1 does not represent a predictive factor for the choice of therapy between oxaliplatin or irinotecan. In patients receiving irinotecan as first-line therapy for mCRC, we did not determine significant differences in response to treatment as measured by CBR or TTP, irrespective of the level of expression of topoisomerase I. Increased expression of p-53 does not represent a predictive factor for the choice of therapy between oxaliplatin or irinotecan. For patients receiving irinotecan as first-line therapy for mCRC, we did not identify significant differences in response to treatment as measured by CBR or TTP, irrespective of the expression level of p-53.