March’s paper of the month looks at the FOxTROT trial, a randomised control trial comparing recurrence rate in patients with locally advanced colon cancer receiving neoadjuvant chemotherapy (NAC) vs. postoperative chemotherapy.

Preoperative chemotherapy for operable colon cancer: Mature results of an international randomized controlled trial
Dion Morton, Matthew Seymour, Laura Magill, Kelly Handley, James Glasbey, Bengt Glimelius, Any Palmes, Jenny Seligmann, Søren Laurberg, Keigo Murakami, Nick West, Philip Quirke, Richard Gray; FOxTROT Collaborative Group
J Clin Oncol, January 2023

What is known about the subject?

A recent systematic review summarised the most relevant studies published on this topic, showing that NAC is safe and well tolerated, with a high compliance rate and improved rates of R0 resection, while maintaining short-term postoperative outcomes. [1]

NAC has some potential advantages over adjuvant therapy in colon cancer:

  1. Early systemic treatment
  2. Shrinking tumour before surgery, which may reduce the risk of incomplete resection
  3. Observable response to treatment

What the study adds?

This study randomised 1,053 patients from 85 centres in the UK, Denmark and Sweden, diagnosed with locally advanced colon cancer (T3 or T4, N0-2, M0) over an 8.5 year period. The primary outcome of the study was recurrent disease within 2 years.

The study showed that NAC with 6 weeks of infusional fluorouracil, leucovorin, and oxaliplatin followed by 18 weeks of infusional fluorouracil, leucovorin, and oxaliplatin postoperatively induced tumour downstaging and allowed more R0 resection (94% vs. 89%, p=0.001), without increasing perioperative morbidity. Moreover, the recurrence rate was significantly lower at 2 years in the NAC group compared to the adjuvant treatment group (17% vs. 23%, p=0.037).

Implications for colorectal practice

This study introduces NAC as a new treatment option for selected patients with locally advanced colon cancer. It is safe and feasible, and it has shown to reduce the rate of local recurrence within 2 years.

The results of the FOxTROT trial need confirmation with further studies in order to standardise the specific treatment and its duration. The ongoing trials FOxTROT 2 or ELECLA will hopefully bring more data about this promising new modality of treatment for locally advanced colon cancer.


  1. Arredondo J, Pastor E, Simó V, Beltrán M, Castañón C, Magdaleno MC, Matanza I, Notarnicola M, Ielpo B. Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review. Tech Coloproctol. 2020 Oct;24(10):1001-1015. doi: 10.1007/s10151-020-02289-4. Epub 2020 Jul 14. PMID: 32666362.

ELECLA trial:

ESCP Affiliates