Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer.

PURPOSE: The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 years. PATIENTS AND METHODS: Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45 (45-Gy RT for 5 weeks with concurrent capecitabine) or CAPOX50 (50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin). Total mesorectal excision was planned 6 weeks after CT-RT. The primary end point was sterilization of the operative specimen, which was achieved in 13.9% versus 19.2% of patients, respectively (P = .09). Clinical results were analyzed for all randomly assigned patients according to the intention-to-treat principle. RESULTS: At 3 years, there was no significant difference between CAP45 and CAPOX50 (cumulative incidence of local recurrence, 6.1% v 4.4%; overall survival, 87.6% v 88.3%; disease-free survival, 67.9% v 72.7%). Grade 3 to 4 toxicity was reported in four patients in the CAP45 group and in two patients in the CAPOX50 group. Bowel continence, erectile dysfunction, and social life disturbance were not different between groups. In multivariate analysis, the sterilization rate (Dworak score) of the operative specimen was the main significant prognostic factor (hazard ratio, 0.32; 95% CI, 0.21 to 0.50). CONCLUSION: At 3 years, no significant difference in clinical outcome was achieved with the intensified CAPOX regimen. When compared with other recent randomized trials, these results indicate that concurrent administration of oxaliplatin and RT is not recommended.

Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2.

PURPOSE: Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin. PATIENTS AND METHODS: We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m(2) twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m(2) twice daily 5 days per week and oxaliplatin 50 mg/m(2) once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR). RESULTS: Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P < .001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P = .09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P = .008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P = .02). CONCLUSION: The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers.

Anal canal carcinoma: early-stage tumors < or =10 mm (T1 or Tis): therapeutic options and original pattern of local failure after radiotherapy.

PURPOSE: To investigate the clinical history, management, and pattern of recurrence of very early-stage anal canal cancer in a French retrospective survey. METHODS: The study group consisted of 69 patients with Stage Tis and T1 anal canal carcinoma < or =1 cm treated between 1990 and 2000 (12 were in situ, 57 invasive, 66 Stage N0, and 3 Stage N1). The median patient age was 67 years (range, 27-83 years). Of the 69 patients, 66 received radiotherapy (RT) and 3 with in situ disease were treated by local excision alone without RT. Twenty-six patients underwent local excision before RT (12 with negative and 14 with positive surgical margins). Of the 66 patients who underwent RT, 8 underwent brachytherapy alone (median dose, 55 Gy), 38 underwent external beam RT (median dose, 45 Gy) plus a brachytherapy boost (median boost dose, 20 Gy), and 20 underwent external beam RT alone (median dose, 55 Gy). RESULTS: Of the 69 patients, 68 had initial local control. Of the 66 patients treated by RT, 6 developed local recurrence at a median interval of 50 months (range, 13-78 months). Four patients developed local failure outside the initial tumor bed. Of the 3 patients with Tis treated by excision alone, 1 developed local recurrence. No relation was found among prior excision, dose, and local failure. The 5-year overall survival, colostomy-free survival, and disease-free survival rate was 94%, 85%, and 89%, respectively. The rate of late complications (Grade 1-3) was 28% and was 14% for those who received doses <60 Gy and 37% for those who received doses of > or =60 Gy (p = 0.04). CONCLUSION: Most recurrences occurred after a long disease-free interval after treatment and often outside the initial tumor site. These small anal cancers could be treated by RT using a small volume and moderate dose (40-50 Gy for subclinical lesions and 50-60 Gy for T1).