Capecitabine and oxaliplatin (CapeOx) regimen demonstrated substantial benefit in advanced colorectal cancer. However using this regimen concurrently with RT in locally advanced rectal cancer showed similar outcomes as capecitabine/RT. The long-term outcomes of preoperative concurrent CapeOx/RT in these patients have been investigated.
We conducted a phase II study to determine the efficacy of preoperative concurrent CapeOx-RT in locally advanced rectal cancer (cT3-4 or N+). Capecitabine 1,650 mg/m2/day was taken on day 1-14 and 22-35 of RT. Oxaliplatin 50 mg/m2was administered on day 1, 8, 22 and 29 of RT. The radiation dose to the pelvis was 45 Gy/25 fractions with a boost dose of 5.4 Gy/3 fractions. The total dose to the tumor bed was 50.4 Gy/28 fractions. Patients underwent surgery after completion of radiotherapy. Dworak tumor regression grading (TRG) was used to determine pathological response. The patients were allowed to receive adjuvant chemotherapy.
Twenty patients were accrued. 55% was male. All patients had clinical T3 N positive disease except one had T4 disease. Pathological response was evaluable in 19 patients. Dworak TRG 1-2 and 3-4 were detected in 36.8% and 63.2% respectively. After median follow-up of 5.93 years, five patients (25%) developed recurrent distant metastatic disease and finally expired. No recurrent disease occurred after 2.39 years. The 5-year DFS and OS were 75% and 80% respectively. Although no statistically significant difference was found, patients with Dworak TRG 1-2 had lower 5-year DFS and OS than those with TRG 3-4 (TRG 1-2, DFS 66.7% vs. TRG 3-4, DFS 100%, p=.058 and TRG 1-2, OS 66.7% vs. TRG 3-4, OS 100%, p=.059 respectively). At present, all patients with Dworak TRG 3-4 are alive and have never had recurrent disease.
Most locally advanced rectal cancer patients receiving preoperative concurrent CapeOx/RT achieved best Dworak TRG. Long-term outcomes of these patients, especially with good response, were excellent. Larger studies may be needed to determine the association of Dworak TRG and survival.
Clinical trial identification
Legal entity responsible for the study
Ramathibodi Comprehensive Cancer Center.
All authors have declared no conflicts of interest.