The results of the now completed NSABP C-07 study confirmed and extended the results of the MOSAIC trial. In NSABP C-07, 2,492 patients with stage II or III colon cancer were randomly assigned to receive either FLOX (2-hour intravenous infusion of 85 mg/m2 oxaliplatin on days 1, 15, and 29 of each 8-week treatment cycle, followed by a 2-hour intravenous infusion of 500 mg/m2 LV plus bolus 500 mg/m2 5-FU 1 hour after the start of the LV infusion on days 1, 8, 15, 22, 29, and 36, followed by a 2-week rest period, for a total of three cycles [24 weeks]) or the same chemotherapy without oxaliplatin (Roswell Park regimen). The 3- and 4-year DFS rates were 71.8% and 67% for the Roswell Park regimen and 76.1% and 73.2% for FLOX, respectively. The hazard ratio was 0.80 (95% confidence interval [CI], 0.69–0.93), a 20% risk reduction in favor of FLOX (P <.004).
Adjuvant chemotherapy following chemoradiation therapy and surgery
Many academic oncologists recommend that FOLFOX be considered the standard for adjuvant chemotherapy in rectal cancer. However, there are no data in rectal cancer to support this consideration. FOLFOX has become the standard arm in the latest Intergroup study evaluating adjuvant chemotherapy in rectal cancer. An Eastern Cooperative Oncology Group trial (ECOG-E5202 [NCI-2009-00562]) randomly assigned patients with stage II or III rectal cancer who have received preoperative or postoperative chemoradiation therapy to 6 months of FOLFOX with or without bevacizumab.
Oxaliplatin with chemoradiation therapy
Oxaliplatin has also been shown to have radiosensitizing properties in preclinical models; and phase II studies combining this agent with fluoropyrimidine-based chemoradiation have reported pathologic complete response (pCR) rates ranging from 14% to 30%.[28,29,30,31,32] Data from multiple studies have demonstrated a correlation between rates of pCR and endpoints including distant metastasis-free survival, DFS, and OS.[33,34,35]
pCR was the primary endpoint (albeit never validated as a true surrogate of OS) in the ACCORD 12/0405-Prodige 2 trial, which randomly assigned 598 patients with clinically staged T2 or T3 or resectable T4 rectal cancer accessible to digital rectal examination to either preoperative radiation (45 Gy in 25 fractions over 5 weeks) with capecitabine (800 mg/m2 twice daily five of every 7 days) or to a higher dose of radiation (50 Gy in 25 fractions over 5 weeks) with the same dose of capecitabine and oxaliplatin (50 mg/m2 weekly). TME was performed in 98% of both groups at a median interval of 6 weeks after chemoradiation was completed. Although a higher percentage of patients achieved a pCR in the oxaliplatin-treated group (19.2% vs. 13.9%), the difference did not reach statistical significance (P = .09). Moreover, the rate of grade 3 or 4 toxicity was significantly higher in the oxaliplatin-treated group (25% vs. 11%, P < .001), and there was no difference in sphincter-sparing surgery (75% vs. 78%). Therefore, there is no current role for off-trial use of concurrent oxaliplatin and radiation in the treatment of patients with rectal cancer.