Neoadjuvant FOLFOXIRI for colorectal cancer – a single-centre retrospective study of outcomes


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Kimberley Durno1,Daniel Krell1,Hemal Ariyaratne1
1Royal Free London NHS Foundation Trust

Abstract

Background

Patients with locally advanced or oligometastatic colorectal cancer who are not initially candidates for surgical resection may become so following neoadjuvant chemotherapy. Randomized data have also shown improved surgical outcomes with neoadjuvant chemotherapy in operable colon cancer. At our centre we have moved towards a more intensive approach with the FOLFOXIRI regimen for suitable patients who require neoadjuvant chemotherapy.

Method

This was a retrospective, single centre study with the primary objective of evaluating the rates of R0 resection after neoadjuvant FOLFOXIRI chemotherapy. Secondary endpoints included toxicity profile and radiological response. Patients received irinotecan 165mg/m2, oxaliplatin 85mg/m2, folinic acid 200mg/m2 and 5-fluorouracil 3200mg/m2 IV infusion over 48 hours every 2 weeks.

Results

11 patients treated with neoadjuvant FOLFOXIRI for colorectal cancer were identified from July 2016 to April 2019. The median age was 50 years (range 32-66). All patients had performance status 0-1. Patients had inoperable locally advanced disease or liver-only metastases. Patients with metastatic disease were RAS-mutant or unknown at time of initiation. The median number of cycles was 5 (range 3-12). 10/11 patients required a chemotherapy dose reduction, either prior to or during treatment. Grade 3 toxicity included febrile neutropenia in two patients and neuropathy in one patient. 9/11 patients (82%) had an objective radiological response, while two had progression. 8/10 (80%) of patients had an R0 resection (outcome pending in one patient).

Conclusion

Patients with initially inoperable colorectal cancer had high response rates and R0 resection rates following treatment with neoadjuvant FOLFOXIRI in this series. Response rates in this small cohort are higher than reported for doublet colorectal chemotherapy regimens in the neoadjuvant setting, despite lower dose intensity. The regimen had a manageable side effect profile with low Grade 3-4 toxicity. Further studies to assess long-term outcomes with the neoadjuvant FOLFOXIRI regimen are recommended, particularly in RAS and BRAF-mutant patients.