A Phase I–II Study on a Gemcitabine-Cyclophosphamide-Fluorouracil/Folinic Acid Triplet Combination in Anthracycline- and Taxane-Refractory Breast Cancer PatientsFrasci G.a · D’Aiuto G.b · Comella P.a · Thomas R.b · Capasso I.b · Botti G.d · Cortino G.R.b · Di Bonito M.d · Rubulotta R.c · Vallone P.c · Comella G.a
Divisions of aMedical Oncology A and bSurgical Oncology A, cDepartment of Radiology and dService of Pathology, National Tumor Institute of Naples, Naples, Italy
Purpose: To define the cyclophosphamide (CTX) maximal tolerated dose when combined with fixed doses of gemcitabine, fluorouracil (5-FU) and folinic acid (leucovorin, LFA) in metastatic breast cancer patients pretreated with anthracyclines and taxanes. Methods: Metastatic breast cancer patients aged ≤75 years, with ECOG performance status 0–2, were eligible, provided that they had received previous anthracycline- and taxane-based chemotherapy for the advanced disease. Chemotherapy consisted of gemcitabine 1,000 mg/m2, 5-FU 425 mg/m2, LFA 100 mg/m2 and escalating doses of CTX, starting from 500 mg/m2, on days 1 and 8 every 3 weeks. The dose escalation was stopped if dose-limiting toxicity (DLT) occured in >33% of patients of a given cohort. After the definition of DLT, a further escalation with the addition of granulocyte colony-stimulating factor (G-CSF; on days 3–5 and 10–12) was planned. Results: Since March 1999, 69 patients have entered this trial through seven different cohorts. The dose escalation was stopped at the CTX dose of 600 mg/m2 since 3/6 patients showed DLT. A further dose escalation was attempted in the presence of G-CSF support. A CTX dose of 800 mg/m2 proved to be safe and was chosen for the phase II. A total of 33 patients were treated at this dose level. The treatment was fairly well tolerated, grade 3–4 neutropenia and thrombocytopenia occurring in 38 and 16% of patients, respectively. No cases of sepsis or bleeding were registered. Four patients required a packed red blood cell transfusion. Severe nonhematologic toxicity was also uncommon, occuring in 10 patients. Three complete and 24 partial responses were recorded for an overall response rate of 38% (95% CI = 26–50). Two complete and 12 partial responses were recorded in the 33 patients treated in the phase II for an overall response rate (ORR) of 42% (95% CI = 25–61). Conclusions: The gemcitabine-CTX-5-FU/LFA combination is a well-tolerated treatment for poor-prognosis breast cancer patients with previous exposure to anthracyclines and taxanes. With the addition of G-CSF, a cumulative CTX dose of 1,600 mg/m2 can be safely delivered every 3 weeks. The evidence of an ORR approaching 40% is very promising and justifies further evaluations in this subset of patients.
© 2002 S. Karger AG, Basel
Division of Medical Oncology A
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Number of Print Pages : 8
Number of Figures : 0, Number of Tables : 7, Number of References : 33
Oncology (International Journal of Cancer Research and Treatment)
Founded 1948 as ‘Oncologia’ by H.R. Schinz; Continued by V. Richards (1967–1975), H. Wrba (1976–1992)
Vol. 62, No. 1, Year 2002 (Cover Date: Released January 2002)
Journal Editor: P.P. Carbone, Madison, Wisc.
ISSN: 0030–2414 (print), 1423–0232 (Online)
For additional information: http://www.karger.com/journals/onc