Issue: 2004 > October > original article

A phase I dose-escalating study of docetaxel plus folinic acid and 5-fluorouracil in anthracyline-pretreated patients with metastatic breast cancer

P.H.Th.J. Slee, C.J. Rodenburg, J.W.R. Nortier, A. van Bochove


Background: Since the need for nonanthracyclinecontaining chemotherapy regimens increases with the increased use of anthracyclines in earlier stages of breast cancer, we investigated the feasibility of the combination of docetaxel and 5-fluorouracil (5-FU) with folinic acid (FA).
Patients and methods: Anthracycline-pretreated patients
with metastatic breast cancer were eligible. Docetaxel was administered as a one-hour infusion every three weeks on day 1, FA 500 mg/m<sup>2</sup> (fixed dose) as a two-hour infusion on days 1 and 15 and 5-FU as a 24-hour infusion on days 1 and 15. The dose levels tested were (docetaxel/5FU in mg/m<sup>2</sup>): 60 /1800, 75/1800, 85/1800, 100/1800, and 100/2100.
Results: Altogether 28 patients were accrued and treated in this multicentre open-label study. Dose-limiting
toxicities (DLTs) were not observed at dose level 1, and in two patients in each of the higher dose levels. DLTs observed were grade III/IV infection (n=4), febrile neutropenia (n=2), diarrhoea (n=1) and erythema (n=1). Partial responses were observed in 10 out of 24 evaluable patients (42%, 95% confidence interval 22.1 to 63.4%). Dose escalation beyond the highest dose level (100/2100) was deemed inappropriate, because these dose levels correspond to recommended dose levels for each drug as a single agent.
Conclusion: Combination of docetaxel (100 mg/m<sup>2</sup>, one-hour infusion q3 weeks on day 1), FA (500 mg/m<sup>2</sup>, two-hour infusion on days 1 and 15) and 5-FU (2100 mg/m<sup>2</sup>, 24-hour infusion on days 1 and 15) is a feasible regimen with encouraging activity in anthracycline-pretreated patients.