New findings from a four-arm phase III clinical trial in patients with stage II or stage III rectal cancer indicate that combining pre-operative (neoadjuvant) radiation with either capecitabine or 5-fluorouracil (5-FU) results in equivalent outcomes.

Capecitabine is an oral drug similar to 5-FU.

This study provides strong clinical evidence that using either 5-FU or capecitabine is acceptable in this setting.

The researchers also found that adding another chemotherapy drug, oxaliplatin, to either of these regimens did not provide further benefit but increased overall treatment toxicity.

“Doctors should feel reassured that they are not giving less effective therapy if they prescribe capecitabine,” said lead study author Carmen Joseph Allegra, MD, a professor of medicine at the University of Florida in Gainesville, Fla. “Oral capecitabine is certainly far more convenient for patients compared to infusional 5-FU. It means taking pills twice a day, rather than undergoing surgery to place an intravenous port and then wearing a pump on their belt for five weeks.”

Early stage rectal cancer is potentially curable with a combination of pre-operative chemotherapy, radiation therapy, surgery, and post-operative chemotherapy. Patients with operable stage II or stage III rectal cancer typically undergo chemotherapy and radiation therapy before surgery to shrink the tumor.

Certain chemotherapy drugs, including 5-FU, capecitabine, and oxaliplatin, act as so-called radiosensitizers—they make the tumours more vulnerable to radiation. Only 5-FU is currently supported by randomised clinical trials data as a radiosensitizer in the preoperative treatment of rectal cancer. Although there hasn’t been any definitive data to support the use of capecitabine in this setting, many doctors suspected it would work as it is effective as an adjuvant treatment for metastatic colorectal cancers and in the adjuvant colon setting.

In this four-arm clinical trial, 1,608 patients were randomly assigned to receive five weeks of radiation therapy plus 5-FU (arm 1, 477 patients); 5-FU and oxaliplatin (arm 2, 329 patients); capecitabine (arm 3, 472 patients); or capecitabine and oxaliplatin (arm 4, 330 patients).

Patients received one of these treatments for five weeks and about a month later underwent surgery to remove the tumour.

There were no significant differences between treatment arms in terms of local-regional control, disease-free survival, and overall survival. The three-year local-regional control rates ranged from 87.4 to 88.2 percent. In cases where surgeons were able to completely remove the tumour (about 95 percent of patients) and no traces of microscopic disease were detected, 2-4 percent of stage II patients and 4-11 percent of stage III patients had a local recurrence within three years after undergoing surgery. And in each of the treatment arms, about 80 percent of patients were still alive five years after surgery.

Infusional 5-FU and capecitabine had similar side effects. Patients who also received oxaliplatin, however, experienced significantly more diarrhea and fatigue.

Dr. Allegra commented that although capecitabine is more expensive than 5-FU, one has to take into account that the overall cost differential for the two therapies also depends on the cost of placing and maintaining the port and pump for 5-FU infusion.

Source: ASCO