The optimal adjuvant chemotherapy for patients with high-risk, early breast cancer should use a dose-dense schedule and should not include fluorouracil, according to researchers.1

Updated results from the GIM2 trial showed that adding fluorouracil to adjuvant chemotherapy did not improve disease-free survival (DFS), but a dose-dense chemotherapy schedule did improve DFS. These results were published in The Lancet Oncology.

The phase 3 GIM2 trial ( Identifier: NCT00433420) enrolled patients with operable, node-positive breast cancer who were 18 to 70 years of age and had an ECOG performance status of 0-1.

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The trial was designed to compare dose-dense chemotherapy (given every 2 weeks) and standard-interval chemotherapy (given every 3 weeks) as well as to compare combination epirubicin, cyclophosphamide, and paclitaxel (ECP) with fluorouracil plus ECP (F-ECP).

There were 502 patients who received dose-dense ECP, 500 who received dose-dense F-ECP, 545 who received standard ECP, and 544 who received standard F-ECP.

At a median follow-up of 15.1 years, the median DFS was 17.09 years in the F-ECP group and was not reached in the ECP group (unadjusted hazard ratio [HR], 1.12; 95% CI, 0.98-1.29; P =.11). The estimated 15-year DFS rate was 55.4% in the F-ECP group and 59.4% in the ECP group.

The median DFS was significantly higher in the dose-dense group than the standard group — not reached and 16.52 years, respectively (HR, 0.77; 95% CI, 0.67-0.89; P =.0004). The estimated 15-year DFS rate was 61.1% in the dose-dense group and 52.5% in the standard group.

In the previously reported analysis of this trial, the most common grade 3-4 adverse events were neutropenia (37% in the standard ECP group, 48% in the standard F-ECP group, 10% in the dose-dense ECP group, and 20% in the dose-dense F-ECP group) and alopecia (44%, 47%, 46%, and 48%, respectively).2  

There were no additional grade 3-4 adverse events with extended follow-up, and there were no treatment-related deaths.1

“Our study robustly showed that fluorouracil should not be added because it increases toxicity without improving outcomes,” the researchers wrote. “The long-term follow-up of the GIM2 trial continues to support the increased efficacy of a dose-dense schedule.”

Disclosures: This research was supported by Bristol-Myers Squibb, Pharmacia, and Dompè Biotech. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


1. Del Mastro L, Poggio F, Blondeaux E, et al. Fluorouracil and dose-dense adjuvant chemotherapy in patients with early-stage breast cancer (GIM2): End-of-study results from a randomised, phase 3 trial. Lancet Oncol. Published online November 9, 2022. doi:10.1016/S1470-2045(22)00632-5

2. Del Mastro L, De Placido S, Bruzzi P, et al. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: An open-label, 2×2 factorial, randomised phase 3 trial. Lancet. 2015;385(9980):1863-72. doi:10.1016/S0140-6736(14)62048-1

This article originally appeared on Cancer Therapy Advisor