title: Irinotecan and radiosensitization in rectal cancer.
abstract: Neoadjuvant radiation therapy with concurrent 5-fluorouracil-based chemotherapy is currently considered the standard of care for locally advanced rectal cancer. Pathologically complete response is a desirable outcome and has been associated with increased disease-free survival. There is a need to improve on this approach given that only approximately 10% achieve a pathologically complete response. Irinotecan has an established role in the treatment of metastatic rectal cancer. Both in-vitro and in-vivo data have shown promising radiosensitization properties. This study provides an overview of the published clinical trials evaluating the role of irinotecan as a radiosensitizer in the management of locally advanced rectal cancer. Although early-phase clinical trials initially showed promising results, this did not translate into improved outcome in a larger randomized phase II trial. Increased topoisomerase I expression has recently been identified as a possible predictive marker for improved response to irinotecan-based radiosensitization. This finding could help identify a subset of patients more likely to benefit from the addition of irinotecan in future trials.
authors.affiliation: Department of Hematology and Oncology, University of Texas Southwestern at Dallas and Dallas VA Medical Center, Dallas, Texas 75201, USA. Henrikb.illum@ va.gov
authors.forename: Henrik
authors.initials: H
authors.lastname: Illum
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D006801:Humans; D000077146:Irinotecan; D015201:Meta-Analysis as Topic; D020360:Neoadjuvant Therapy; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D000077146:Irinotecan; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin