FoXTROT results: preoperative chemo could become new standard

Nov 1 2012

Preoperative chemotherapy is a feasible option for resectable advanced colon cancer, show results of the FoXTROT trial.

FoXTROT (Fluoropyrimidine Oxaliplatin and Targeted Receptor Pre-Operative Therapy) trial findings indicate that preoperative treatment in stage 3 and 4 tumors could induce downstaging within 6 weeks. Furthermore, the authors found no increase in surgical morbidity or mortality compared with standard postoperative chemotherapy.

"We have shown that patients with locally advanced, but resectable, colon cancer can be appropriately selected for neoadjuvant chemotherapy with CT [computed tomography] scanning…and can safely undergo preoperative chemotherapy followed by colonic resectional surgery," say the FOxTROT Collaborative Group.

Chemotherapy was given in 2-week cycles by the standard UK modified de Gramont regimen. This consists of oxaliplatin 85 mg/m², l-folinic acid 175 mg/m² plus fluorouracil 400 mg/m² bolus, followed by a 2400 mg/m² 46-hour infusion.

Between May 2008 and September 2010, 99 patients were randomly assigned to receive preoperative chemotherapy for three cycles before surgery and nine cycles after surgery, while 51 patients received 12 cycles of postoperative chemotherapy.

Patients who tested positive for KRAS wild-type tumors were also randomly assigned to receive an anti-epithelial growth factor receptor antibody during the first 6 weeks of therapy. All patients had their tumor staged using CT.

All patients in the preoperative group underwent resectional surgery, as did 94% of patients in the postoperative group.

The authors found no significant differences between complication rates, such as anastomotic leak, wound infections, or a need for further surgery. The median time to hospital discharge was 7 days in the preoperative group and 6 days in the postoperative group. Toxicity was also comparable between the two groups.

However, the authors did find significant differences in the rate of apical node involvement (1 vs 20%), and resection margin involvement (4 vs 20%) in favour of preoperative chemotherapy. Furthermore, 31% of tumors in the preoperative group showed moderate to complete regression at surgery compared with just 2% in the postoperative group. However, explain the authors, further research will be needed to explore whether these findings translate to improved survival.

"On the basis of these promising findings from the pilot phase, proceeding the ongoing FOxTROT phase 3 study is appropriate; we aim to enroll at least a further 900 patients," they write in the Lancet Oncology.

In an accompanying editorial, Andres Cervantes (University of Valencia, Spain) says that these results are needed before clinical practice can change. "Until the final analysis takes place, it is not known if there is a survival advantage with preoperative chemotherapy.

"If it is, preoperative or neoadjuvant therapy followed by surgery would be a preferred option for patients with locally advanced colon cancer."

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