Estephan F, Valero V, Esteva FJ, Mejia JA, Frye DK, Ibrahim NK
Phase I study of prolonged-infusion gemcitabine combined with cyclophosphamide in patients with metastatic carcinoma of the breast: tolerability of an optimal dose schedule. [Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't]
Oncology 2009; 77(1):63-70.
BACKGROUND: A phase I study was initiated to determine the maximum tolerated dose (MTD) of prolonged-infusion gemcitabine combined with cyclophosphamide in patients with metastatic breast carcinoma (MBC).
METHODS: Patients with MBC were treated with gemcitabine infusion at 10 mg/m2/min and cyclophosphamide by intravenous piggyback injection, 4 h after initiation of the infusion. We treated 3-6 patients at a particular dose level until the MTD was determined.
RESULTS: Overall, 44 patients received a total of 197 courses of therapy. Both drugs were given on days 1, 8 and 15 to 14 patients (68 courses). Delayed white blood cell recovery necessitated first protocol amendment to drop cyclophosphamide on days 8 and 15 in 9 patients (43 cycles). A second amendment was needed to drop gemcitabine on day 15 because of thrombocytopenia in 21 patients (86 courses). The dose-limiting toxicity was thrombocytopenia. The MTD of an optimal dose schedule was 800 mg/m2 gemcitabine infused at a rate of 10 mg/m2/min on days 1 and 8, and 400 mg/m2 cyclophosphamide, by intravenous piggyback injection, on day 1, 4 h after initiation of the gemcitabine infusion.
CONCLUSIONS: The MTD can be given safely every 4 weeks to patients with MBC. Phase II studies are warranted to evaluate the clinical activity of this therapy.
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