Chemotherapy Does Not Improve Survival in Rectal Cancer

Zosia Chustecka

September 13, 2006

September 13, 2006 — In patients with resectable rectal cancer receiving preoperative radiotherapy, the addition of chemotherapy, either before or after surgery, had no significant effect on survival. It did, however, improve local control, concludes a European study in the September 13 New England Journal of Medicine.

It may be worth considering the option of adding preoperative chemotherapy in some patients, the researchers comment, as it resulted in a high rate of local control. Tumors were significantly smaller than after preoperative radiation alone and had less advanced pathological tumor stages and pathological nodal status (P < .001). There was also less frequent lymphatic, venous, and perineural invasion (P = 0.008). However, there was no effect on survival, the group points out. "The 5-year cumulative incidence of distant metastases was about 3 times that of local recurrences, indicating that future trials should focus on eradicating micrometastases."

Study Spanned 10 European Countries

The European Organization for Research and Treatment of Cancer (EORTC) Radiotherapy Group Trial 22921 spanned 10 countries and involved 1011 patients. Funding came from the EORTC, the US National Cancer Institute, and 2 French research groups. Preliminary results were reported at the American Society of Clinical Oncology meeting last year, and now the researchers, led by Jean-Francois Bosset, MD, from the University of Franche-Compte, in Besançon, France, report full details.

Patients had clinical stage T3 or T4 resectable rectal cancer and underwent preoperative radiotherapy, 45 Gy over 5 weeks. This is the current recommended treatment for such patients, the researchers comment, and the control group in the trial followed this regimen.

Three other groups (with 253 patients in each) received chemotherapy in addition to radiation. Chemotherapy consisted of fluorouracil and leucovorin at 350 mg and 20 mg, respectively, per square meter of body surface per day. The preoperative group received 2 courses of chemotherapy, on week 1 and week 5 of radiotherapy. The postoperative group started chemotherapy 3 to 10 weeks after surgery and received 4 courses delivered every 3 weeks. A third group of patients received chemotherapy both before and after surgery.

There were no significant differences between the groups in survival. The 5-year overall survival rate was 65.8% vs 64.8% in the groups with and without preoperative chemotherapy (P = .84), respectively, and 67.2% vs 63.2% in those with and without postoperative chemotherapy (P = .12). The 5-year disease-free survival rates were 56.1% vs 54.4% for the groups with and without preoperative chemotherapy (P = .52) and 58.2% vs 52.2% for those with and without postoperative chemotherapy (P = .13).

Dr. Bosset and colleagues comment that adherence to chemotherapy administered before surgery was excellent, but adherence to postoperative chemotherapy was poor. Less than half of the patients assigned to this treatment received it according to the protocol. When only these patients are considered (ie, only those who received all the treatment), there is a difference between those who had postoperative chemotherapy and those who did not. The survival curves diverged after 2 years for progression-free survival and after 4 years for overall survival, and this effect did not diminish with time, they write.

N J Eng Med. 2006;355:1114-1123.


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