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.

Is There a Best Radiosensitizing Agent in the Treatment of Locally Advanced Rectal Cancer?

“…Furthermore, irinotecan is metabolized to SN-38, a more active metabolite. In vitro studies found synergy was dependent on drug concentration and timing, with increased radiosensitivity present only when the drug was present at the time of, or shortly after (24-48 h.) radiation [51,52].…”

Systematic review of treatment intensification using novel agents for chemoradiotherapy in rectal cancer

“…Despite the promise of the above studies, no phase III trial of concurrent irinotecan has yet been reported. This will be rectified in the future by the ongoing UK ARISTOTLE trial, which will complete accrual (target 600 patients) in mid‐2018.…”

“…Despite the promise of the above studies, no phase III trial of concurrent irinotecan has yet been reported 58 .…”

Phase I dose escalation trial of nitroglycerin in addition to 5-fluorouracil and radiation therapy for neoadjuvant treatment of operable rectal cancer

“…8 Several chemotherapeutic agents that have improved survival in the adjuvant or metastatic setting for the management of colon cancer have been evaluated as possible radiosensitizers in rectal cancer. 9 These agents include irinotecan, 10 oxaliplatin, 11 bevacizumab, 12 and cetuximab. 12 However, none of these compounds has demonstrated superiority to 5-FU in terms of achieving a substantially increased rate of pCR.…”