Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer--the RAPIDO trial

Per J Nilsson, Boudewijn van Etten, Geke A P Hospers, Lars Påhlman, Cornelis J H van de Velde, Regina G H Beets-Tan, Lennart Blomqvist, Jannet C Beukema, Ellen Kapiteijn, Corrie A M Marijnen, Iris D Nagtegaal, Theo Wiggers, Bengt Glimelius, Per J Nilsson, Boudewijn van Etten, Geke A P Hospers, Lars Påhlman, Cornelis J H van de Velde, Regina G H Beets-Tan, Lennart Blomqvist, Jannet C Beukema, Ellen Kapiteijn, Corrie A M Marijnen, Iris D Nagtegaal, Theo Wiggers, Bengt Glimelius

Abstract

Background: Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer.

Methods and design: Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life.

Discussion: Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer.

Trial registration: ClinicalTrials.gov NCT01558921.

Figures

Figure 1
Figure 1
Treatment algorithm.

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