SUMMARY: The American Cancer Society estimates 39,220 new cases of Rectal cancer will be diagnosed in the United States in 2016. Rectal cancer diagnosed at an early stage such as Stage II (T3-T4, N0) or Stage III (Node positive disease without distant metastases) is potentially curable with a combination of neoadjuvant (preoperative) chemoradiation, surgery and postoperative chemotherapy. Unlike colon cancer, the risk of locoregional recurrence is high in Rectal cancer due to its close proximity to the surrounding pelvic organs and difficulty in obtaining a clear surgical margins. Further, there is no serosal tissue surrounding the rectum. For all these reasons, preoperative Radiation Therapy (RT) with concurrent Fluoropyrimidine based chemotherapy as a radiosensitizer, followed by postoperative chemotherapy, has been the standard intervention. Radiation consists of 45 Gy delivered in 25 fractions 5 days a week with a 5.4 Gy boost. Concurrent chemotherapy in the US has included 5-FU/Leucovorin, single agent 5-FU or single agent XELODA® (Capecitabine).
The authors in this study evaluated the efficacy of a short course of neoadjuvant radiation therapy for patients with unresectable cT3 or cT4 Rectal adenocarcinoma. The trial included 515 patients who were randomly assigned either to the control group (N=254), in which patients received RT at 50.4 Gy delivered in 28 fractions, given simultaneously with a regimen of 5-FU bolus, Leucovorin and ELOXATIN® (Oxaliplatin) or the experimental group (N=261) in which patients received a short Five day course of Radiotherapy at 5 Gy per day (Total 25 Gy), followed by three courses of FOLFOX4 delivered over 48 hours, during weeks 3, 5, and 7. Both treatment groups underwent surgery approximately 12 weeks after radiation was started and about 6 weeks following neoadjuvant treatment. ELOXATIN® inclusion in the chemotherapy regimen was at the discretion of the treating physician, due to increase in toxicity. Nonetheless, 70% of the patients had received ELOXATIN® at the end of the study. It should be noted that the NSABP protocol R-04 demonstrated that the addition of ELOXATIN® in the neoadjuvant chemotherapy regimen did not improve outcomes but resulted in significant toxicity. The median follow up was 35 months.
The primary endpoint of the rate of curative resection (R0) was 71% in the control group versus 77% in the experimental group. Pathological Complete Response rates were 11.5% in the control group and 16% in the experimental group. The 3 year Overall Survival rates for the control versus experimental group were 65% vs 73% and Disease Free Survival for the control versus experimental group were 52% vs 53%. These differences were not statistically significant. The local failure rates were similar in both treatment groups (22%).
The authors concluded that a short course of radiotherapy combined with three cycles of chemotherapy post radiation, can be more convenient with lower toxicity and this regimen would be an appealing option for patients with locally advanced Rectal cancer, with metastases in liver or lungs, for whom chemotherapy to control systemic disease can be started much earlier, following a short course of radiation therapy. Neoadjuvant chemoradiation for fixed cT3 or cT4 rectal cancer: Results of a Polish II multicentre phase III study. Bujko K, et al. J Clin Oncol 34, 2016 (suppl 4S; abstr 489)