NEW YORK (Reuters Health) - In nonresectable rectal cancer, the addition of chemotherapy to radiotherapy, compared with radiotherapy alone, improves local control and prolongs time to treatment failure and cancer-specific survival, results of a randomized phase III study confirm.

It is generally accepted, the study team notes, that patients with locally advanced nonresectable rectal carcinoma should receive radiotherapy 5 to 8 weeks before surgery. "The purpose of the radiotherapy is to obtain downstaging of the primary tumor to permit an R0 resection, and to sterilize the pelvic area at risk, reducing local recurrence rate and improving survival," they explain in the August 1 Journal of Clinical Oncology.

However, "The value of concomitant and adjuvant chemotherapy in these cases has previously not been proven in randomized trials, although there were indications from phase II studies of better efficacy from such combinations," Dr. Morten Braendengen from Ulleval University Hospital, Cancer Centre, Oslo, Norway and colleagues point out.

In their study, 207 patients with locally nonresectable T4 primary rectal carcinoma or local recurrence from rectal carcinoma were randomly allocated to either chemotherapy (fluorouracil/leucovorin) administered concurrently with radiotherapy (50 Gy) and adjuvant for 4 months after surgery (n = 98), or to 50 Gy radiotherapy alone (n = 109).

According to the researchers, chemoradiotherapy (CRT) was superior to radiotherapy (RT) alone. The local control rate at 5 years was 82% with CRT versus 67% with RT. Time to treatment failure was also statistically significantly different, with 63% failure-free in the CRT group compared with 44% in the RT group at 5 years.

With CRT, cancer-specific survival and overall survival at 5 years were 72% and 66%, respectively, versus 55% and 53%, respectively, with RT.

Overall, the treatments were well tolerated, according to the team. Grade 3 or 4 toxicity, mainly gastrointestinal, was seen in 29% of CRT patients versus 6% of RT patients.

"This randomized phase III study confirms that the addition of chemotherapy to radiotherapy improves outcome both concerning local and systemic control," Dr. Braendengen and colleagues conclude.

J Clin Oncol 2008;26:3687-3694.

Copyright Reuters 2008. Click for Restrictions