Chemoradiation is the preferred approach to upfront treatment of rectal cancer whenever possible.
“Chemoradiation” refers to the carefully orchestrated simultaneous administration of chemotherapy and radiation treatments. Chemoradiation is an important tool in the treatment of rectal cancer. The term “neoadjuvant” refers to the concept of administering chemotherapy and/or radiation therapy prior to surgery. The purpose of neoadjuvant chemoradiation therapy is twofold: to shrink a tumor to facilitate subsequent surgical removal and to improve a patient’s chance for cure. Alternatively, patients with rectal cancer of a size and location that permit resection first should subsequently have adjuvant chemoradiation therapy to improve their chance for a cure.
A typical chemoradiation regimen might consist of daily (Monday through Friday) radiation treatments concurrent with daily (Monday through Friday) continuous infusion 5-fluorouracil (5-FU). This chemoradiation is typically given over a period of five to six weeks. Chemotherapy is given with radiation therapy in order to sensitize tumor cells to radiation, and because the combination has been shown to be more effective than the use of either modality alone. Continuous infusion rather than bolus (a daily 5-10 minute infusion) chemotherapy is preferred as it has resulted in improved survival rates in one study. This regimen may be given pre- or postoperatively for locally advanced tumors (T3/T4 or N1/N2) where it has been shown to reduce the chance of tumor recurrence and improve the chance for cure.
With Xeloda alone, there are two supportive adjuvant phase II studies. Xeloda simulates continuous infusion 5FU and can substitute for it however, the combination of Xeloda and Oxaliplatin is still being investigated with radiation. A phase I/II study from the UK has determined the MTD of continuous (7 days) oral capecitabine administered twice daily in combination with oxaliplatin 130 mg/m2 on days 1 and 29, and pelvic radiotherapy in patients with borderline or unresectable rectal cancer. Now that this study is complete, the regimen is likely to be evaluated in a larger randomised phase III trial.
A German Group performed a phase I study to determine the MTD of oxaliplatin when administered with capecitabine and standard radiotherapy, and extended to a phase II neoadjuvant study in 32 patients with LARC or low-lying rectal cancer. A Belgian trial has used capecitabine 5 days per week given on weekdays only (i.e. capecitabine 825 mg/m2 twice daily on weekdays plus weekly low-dose oxaliplatin 50 mg/m2 on days 1, 8, 15, 22 and 29 plus radiotherapy 45 Gy in 1.8 Gy daily fractions for 5 weeks. This same regimen has also been evaluated in the larger international phase II CORE (capecitabine, oxaliplatin, radiotherapy and excision) study.
Another small dose-finding study is evaluating a similar chemoradiation regimen (capecitabine 725–900 mg/m2 twice daily on weekdays plus escalating doses of oxaliplatin 50 mg/m2, 60 mg/m2, 70 mg/m2 on days 1, 8, 15, 22 and 29 plus radiotherapy 45 Gy in 1.8 Gy daily fractions for 5 weeks). Finally, an ongoing Italian study is examining preoperative capecitabine and oxaliplatin with high-dose pelvic conformal radiotherapy in Locally Advanced Rectal Cancer.
The current findings from the above studies suggest that preoperative capecitabine and oxaliplatin chemoradiation is effective and generally well tolerated, although more robust toxicity data on weekly schedules of oxaliplatin is required. For this reason, a large, phase III pan-European trial (PETACC-6) comparing capecitabine and oxaliplatin chemoradiation with capecitabine chemoradiation alone as adjuvant treatment in T3/4 N1/2 patients is in development. It is recommended by NCCN(REC-4).
Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731-1740
G. A. Hospers, C. J. A. Punt, M. E. Tesselaar, A. Cats, K. Havenga, J. W. H. Leer, C. A. Marijnen, E. P. Jansen, H. H. J. M. Van Krieken, T. Wiggers, et al.
Preoperative Chemoradiotherapy with Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer. A Phase I II Multicenter Study of the Dutch Colorectal Cancer Group
Ann. Surg. Oncol., October 1, 2007; 14(10): 2773 – 2779.
C. Aschele and S. Lonardi
Multidisciplinary treatment of rectal cancer: medical oncology.
Ann. Onc., November 1, 2007; 18(11): 1908 – 1915.
R. Glynne-Jones and M. Harrison
Locally Advanced Rectal Cancer: What Is the Evidence for Induction Chemoradiation?
Oncologist, November 1, 2007; 12(11): 1309 – 1318.