FOxTROT: Randomized phase II study of neoadjuvant chemotherapy (CT) with or without an anti-EGFR monoclonal antibody for locally advanced, operable colon cancer: Planned interim report.

Abstract

3568 Background: Preoperative CT and radiotherapy are surprisingly more effective than postoperative treatment in rectal and other cancers, perhaps because micrometastases are more readily eradicated by neoadjuvant CT than CT given after the delay and immunological stress of surgery. Or, shrinking tumours before surgery may reduce the risk of incomplete excision and tumour cell shedding during surgery. Pre-operative CT also provides a unique opportunity to identify tumour markers predictive of response to CT and anti-EGFR therapy. Methods: The FOxTROT pilot study randomised 150 patients with potentially curative locally advanced colon cancer from 35 UK centres between neoadjuvant and standard CT. Patients with radiologically staged high-risk T3 (invasion ≥5mm beyond the muscularis propria) or T4 cancer received three 2-week cycles of OxMdG (oxaliplatin 85 mg/m2, l-folinic acid 175mg, 5-FU 400 mg/m2 bolus then 2400 mg/m2 by 46h infusion) followed by surgery and a further nine cycles of post-operative CT, or surgery followed by 12 cycles of the same CT (randomised 2:1). KRAS wildtype patients were also randomised 1:1 to receive panitumumab (6 mg/kg; 2-weekly) with the first 6 weeks of CT or control. Results: Neoadjuvant CT was delivered to schedule in 85% of patients with grade 34 toxicity in <10% of patients. Only one had surgery delayed (neutropenia) and there were no significant differences in post operative morbidity or hospital stay compared to the control group. There were 2 pathological complete responses (pT0) and 6 pT2 tumours in 88 neoadjuvant CT patients compared to one pT2 in 43 controls. 2% vs 17% of apical nodes were positive (p=0.003) and tumour regression was graded as moderate or more for 22% vs 0% (p<0.0001). Conclusions: Neoadjuvant CT for primary colon cancer can be delivered with acceptable toxicity and perioperative morbidity and an encouraging pathological response. The ongoing phase III trial will determine whether long term benefits are realisable.