mFOLFOX6 Plus Radiation Improved pCR in Advanced Rectal Cancer

Undergoing neoadjuvant treatment with mFOLFOX6 (leucovorin/fluorouracil [FU]/oxaliplatin) plus radiation therapy resulted in higher rates of pathologic complete response (pCR) in patients with locally advanced rectal cancer compared with preoperative 5-FU plus radiation or mFOLFOX6 alone, according to preliminary results of the FOWARC study (abstract 3500) presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.

Additionally, neoadjuvant mFOLFOX6 alone produced similar rates of downstaging with less toxicity and postoperative complications compared with the 5-FU/radiation combination.

“As mFOLFOX6 with radiation is feasible and achieved higher pCR rate as well as good response rate, mFOLFOX6 with radiation may replace 5-FU as standard treatment in this setting,” said presenter Jianping Wang, MD, of Sun Yat-sen University in Guangzhou, China.

According to Wang, preoperative 5-FU–based chemoradiation is the standard treatment for patients with locally advanced rectal cancer; however, it is not effective on distant metastases. The use of radiation in these patients causes concerns about anal and sexual function.

“Due to the high incidence of rectal cancer in China, a lot of hospitals do operations for these patients but the facility of radiation is not widely available,” Wang said. “In order to avoid unnecessary radiotherapy, the strategy of upfront neoadjuvant treatment with mFOLFOX6 is worthy of investigation.”

The FOWARC study included 495 patients with clinical stage II to III rectal cancer within 12 cm of the anal verge. The patients were randomly assigned to one of three arms: 5-FU with radiation, mFOLFOX6 with radiation, or 4 to 6 cycles of mFOLFOX6 alone. The primary endpoint of the analysis was 3-year disease-free survival. Wang presented preliminary results of the trial.

The rate of R0 resection was similar between the three treatment arms: 5-FU/radiation, 90.2%; mFOLFOX6/radiation, 89.5%; and mFOLFOX6 alone, 91.2%.

Two pathologists blinded to treatment group conducted an evaluation of pCR and found that patients assigned to mFOLFOX6 plus radiation had a significantly higher rate at 28% compared with 5-FU/radiation (14.3%) and mFOLFOX6 alone (6.1%; P = .001). Downstaging was achieved in 57.4% of patients assigned mFOLFOX6/radiation, 35.8% of patients assigned mFOLFOX6 alone, and 37.6% of patients assigned 5-FU/radiation.

Patients who underwent treatment with radiation had a significantly higher rate of surgical complications. Anastomotic leakage occurred in 21.1% of patients assigned 5-FU/radiation and 18.2% of patients assigned mFOLFOX6/radiation compared with 6.8% of patients assigned mFOLFOX6 alone (P = .020). Infection of incision occurred in 22.6% of patients assigned 5-FU/radiation, 16.8% of patients assigned mFOLFOX6/radiation, and 6.1% of patients assigned mFOLFOX6 alone (P = .009).

The researchers also looked at outcomes in a subgroup of patients with low rectal cancer-a tumor located within 5 cm from the anal verge. The pCR rate in these patients was higher in those assigned mFOLFOX6/radiation (29.2%) compared with 5-FU/radiation (15.6%) and mFOLFOX6 alone (6.6%).