Phase I Study of Prolonged-Infusion Gemcitabine Combined with Cyclophosphamide in Patients with Metastatic Carcinoma of the Breast: Tolerability of an Optimal Dose Schedule

Vol. 77, No. 1, 2009

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Clinical Study

Phase I Study of Prolonged-Infusion Gemcitabine Combined with Cyclophosphamide in Patients with Metastatic Carcinoma of the Breast: Tolerability of an Optimal Dose Schedule
Fadi Estephan^{a, b}, Vicente Valero^a, Francisco J. Esteva^a, Jaime A. Mejia^a, Debra K. Frye^a, Nuhad K. Ibrahim^a

^aDepartment of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Tex., and
^bSection of Medical Oncology, The University of Texas Medical Branch, Galveston, Tex., USA

Address of Corresponding Author

Oncology 2009;77:63-70 (DOI: 10.1159/000226213)

Key Words

Advanced breast cancer
Gemcitabine
Cyclophosphamide
Phase I

Abstract

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.

Author Contacts

Nuhad K. Ibrahim, MD
Department of Breast Medical Oncology
The University of Texas M.D. Anderson Cancer Center
1155 Pressler Street, CPB5.3540, Houston, TX 77230-1439 (USA)
Tel. +1 713 792 2817, Fax +1 713 794 4385, E-Mail nibrahim@mdanderson.org

Article Information

Received: September 18, 2008
Accepted after revision: January 23, 2009
Published online: June 26, 2009
Number of Print Pages : 8
Number of Figures : 0, Number of Tables : 5, Number of References : 25

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