No benefit from infusional chemotherapy in early breast cancer
MedWire News: For patients with early-stage breast cancer, adjuvant treatment with intravenous epirubicin, cisplatin, and 5-fluorouracil (5-FU; ECisF) shows no benefit in terms of reducing relapse rates over 5-FU, epirubicin, and cyclophosphamide (FEC60), study results show.
The findings concur with the Trial Of Preoperative Infusional Chemotherapy (TOPIC), which similarly found no benefit in infusional versus conventional chemotherapy.
The ECisF regimen has been shown to be highly active in the treatment of advanced metastatic breast cancer. To assess if this benefit is translated to patients with early-stage disease, two phase III multi-center trials were instigated, the first being TOPIC. The second, reported here, is the trial of adjuvant 5-FU infusional chemotherapy (TRAFIC).
In the TRAFIC study Ian Smith (The Royal Marsden NHS Foundation Trust, Surrey, UK) and colleagues randomly assigned 349 women to receive intravenous ECisF (epirubicin 60 mg/m2, day 1, cisplatin 60 mg/m2, day 1, and 5-FU 200 mg/m2 by daily 24-h infusion [n=172]) or FEC [5-FU 600 mg/m2, day 1, epirubicin 60 mg/m2, day 1, and cyclophosphamide 600 mg/m2, day 1 [n=177]).
Both treatments were delivered every 3 weeks for six cycles, and all randomized patients were included in the intent-to-treat population. The primary end point was relapse-free interval.
The researchers explain that TRAFIC was powered to detect a 40% (ie, a hazard ratio [HR] of 0.6) relative reduction in the relapse rate attributable to infusional EcisF, because such a large reduction was felt to be necessary to compensate for the added side-effects and inconvenience of the regimen.
After a median follow-up of 112 months there were 62 relapse events in the ECisF group and 70 in the FEC60 group.
Kaplan-Meier survival curves for relapse-free interval showed that ECisF provided a nonsignificant 16% reduction in relapse compared with FEC60 (HR=0.84, 95% confidence interval: 0.60-1.19).
Thus, the lower confidence interval for the observed HR corresponded to the target 40%, although Smith and colleagues note that the true benefit is highly unlikely to be this large.
They note that since planning the TRAFIC trial in 1995, capecitabine has largely replaced infusional 5-FU in the treatment of advanced breast cancer and is now being tested in adjuvant and neoadjuvant regimens, sometimes in combination with a taxane.
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By Andrew Czyzewski