Neoadjuvant treatment (FOLFOX4 plus hypofractionated tomotherapy) for patients with locally advanced rectal cancer: a multicenter phase II trial

Alessandro Passardi, Ilario Giovanni Rapposelli, Emanuela Scarpi, Elisa Neri, Elisabetta Parisi, Giulia Ghigi, Giorgio Ercolani, Andrea Avanzolini, Davide Cavaliere, Britt Rudnas, Martina Valgiusti, Domenico Barone, Fabio Ferroni, Giovanni Luca Frassineti, Antonino Romeo, Alessandro Passardi, Ilario Giovanni Rapposelli, Emanuela Scarpi, Elisa Neri, Elisabetta Parisi, Giulia Ghigi, Giorgio Ercolani, Andrea Avanzolini, Davide Cavaliere, Britt Rudnas, Martina Valgiusti, Domenico Barone, Fabio Ferroni, Giovanni Luca Frassineti, Antonino Romeo

Abstract

Aims: This study aims to evaluate the safety and efficacy of a new neoadjuvant regimen (FOLFOX4 plus hypofractionated tomotherapy) in patients with locally advanced rectal cancer.

Methods: Patients with stage II-III rectal cancer were treated with the pre-operative chemoradiotherapy regimen comprising FOLFOX4 (two cycles), TomoTherapy (25 Gy in five consecutive fractions, one fraction per day in 5 days on the clinical target volume at the isodose of 95% of the total dose), FOLFOX4 (two cycles), followed by surgery with total mesorectal excision and adjuvant chemotherapy with FOLFOX4 (eight cycles). The primary endpoint was pathological complete response (pCR).

Results: Fifty-two patients were enrolled and 50 patients were evaluable. A total of 46 (92%) patients completed chemoradiotherapy according to the study protocol and 49 patients underwent surgery. Overall, 12 patients achieved a pCR (24.5%, 95% CI 12.5-36.5). The most common grade 3 or more adverse events were neutropenia and alteration of the alvus. Adverse reactions due to radiotherapy, mainly grade 1-2 dermatitis, tenesmus, urinary dysfunction and pain, were tolerable and fully reversible. The most important surgical complications included infection, anastomotic leakage and fistula, all resolved with conservative treatment.

Conclusion: FOLFOX and hypofractionated TomoTherapy is effective and safe in patients with locally advanced rectal cancer. Long-term efficacy needs to be further evaluated.

Trial registration: ClinicalTrials.gov identifier: NCT02000050 (registration date: 26 November 2013) https://ichgcp.net/clinical-trials-registry/NCT02000050.

Keywords: concurrent chemoradiotherapy; neoadjuvant treatment; rectal cancer; tomotherapy.

Conflict of interest statement

Conflict of interest statement: The authors declare that there is no conflict of interest.

© The Author(s), 2020.

Figures

Figure 1.
Figure 1.
Study treatment. *FOLFOX4: oxaliplatin 85 mg/m² IV: day 1, levofolinate 100 mg/m² IV: day 1–2, 5-fluorouracil 400 mg/m² IV in bolus and 600 mg/m² IV infusion over 22 h: day 1–2; every 2 weeks. **25 Gy in five consecutive fractions, one fraction per day in 5 days, using helical Tomo Therapy or linear accelerator (LINAC) with an intensity modulated RT (IMRT) or a volumetric modulated arc therapy (VMAT) technique.
Figure 2.
Figure 2.
(A) Progression-free survival (PFS) of 50 patients with locally advanced rectal cancer. Vertical bars represent 95% confidence interval of survival probability at 1 and 2 years; and (B) Overall survival (OS) of 50 patients with locally advanced rectal cancer. Vertical bars represent 95% confidence interval of survival probability at 1 and 2 years.

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