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 five to eight 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 four 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 five years was 82 per cent with CRT versus 67 per cent with RT. Time to treatment failure was also statistically significantly different, with 63 per cent failure-free in the CRT group compared with 44 per cent in the RT group at five years.
With CRT, cancer-specific survival and overall survival at five years were 72 per cent and 66 per cent, respectively, versus 55 per cent and 53 per cent, respectively, with RT.
Overall, the treatments were well tolerated, according to the team. Grade three or four toxicity, mainly gastrointestinal, was seen in 29 per cent of CRT patients versus six per cent 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
