A phase II trial of preoperative concurrent chemotherapy and dose escalated intensity modulated radiotherapy (IMRT) for locally advanced rectal cancer

Objectives: To determine the pathological response rates and toxicity and in patients with locally advanced rectal cancer treated with concurrent capecitabine and dose escalated intensity modulated radiotherapy (IMRT) Methods: Patients with stage II or III adenocarcinoma of the rectum were treated with preoperative concurrent capecitabine and IMRT.Dose of capecitabine was 825mg/m 2 , 5 days a week for 5 weeks.IMRT was used to deliver a dose of 45Gy in 25 fractions (1.8Gy per fraction daily, 5 days a week over 5 weeks) to the regional lymphatics and areas at risk of harbouring microscopic disease.A concomitant synchronous integrated boost (SIB) to the gross tumour with a margin to a total dose of 55Gy in 25 fractions was also delivered in the same period.TME surgery was performed 8 weeks after preoperative therapy.The primary endpoint is pathological complete response rate (pCR) and the secondary endpoint was downstaging rates, Sphincter preservation rates (SPR), disease free survival (DFS) at 2 years and toxicity graded using the CTCAE v3.0.Results: Twenty three patients were enrolled.Three were not evaluable; one did not complete treatment due to logistic issues and two declined surgery.The remaining 20 patients completed preoperative chemoIMRT followed by TME surgery.At a median follow-up of 38.2 months (17.5-53.2months), 90% (18 of 20) patients were alive.The 2 year overall survival and DFS were 90% and 90% respectively.35%(7/20) of patients had a pCR.65% (13 of 20) patients had successful downstaging of their rectal tumours.There was no local recurrence.Sphincter preservation rate was 85%.Treatment was well tolerated with only one patient (5%) having Grade 3 radiation proctitis.Conclusions: Preoperative concurrent capecitabine and dose escalated IMRT is well tolerated and results in high rates of pCR.A randomized trial comparing this regimen with standard 3D conformal chemoradiotherapy is warranted.