AUTHOR=Engels Benedikt , Gevaert Thierry , Sermeus Alexandra , De Ridder Mark TITLE=Current Status of Intensified Neo-Adjuvant Systemic Therapy in Locally Advanced Rectal Cancer JOURNAL=Frontiers in Oncology VOLUME=Volume 2 - 2012 YEAR=2012 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2012.00047 DOI=10.3389/fonc.2012.00047 ISSN=2234-943X ABSTRACT=The addition of 5-fluorouracil (5-FU) or its prodrug capecitabine to radiotherapy (RT) is a standard approach in the neo-adjuvant treatment of patients with rectal tumors extending beyond the muscularis propria (stage II) and/or with clinical evidence of regional lymph node metastases (stage III). According to European randomized trials, the combined treatment modality resulted in favorable local control (LC) rates as compared with radiotherapy (RT) alone, but no improvement was found regarding the occurrence of distant metastases or overall survival (OS). In an effort to further enhance the response rates and to decrease the high incidence of distant metastases in locally advanced rectal cancer patients, the addition of other chemotherapeutical drugs and biologic agents as radiation sensitizers to neo-adjuvant 5-FU based chemoradiotherapy (CRT) has been recently investigated. The role of those agents is however questionable as first results from phase III data do not show improvement on pathologic complete remission (pCR) and circumferential resection margin (CRM) negative resection rates as compared to 5-FU based CRT, nevertheless an increased toxicity.