Gemcitabine/cyclophosphamide/5-fluorouracil/folinic acid triplet combination in anthracycline- and taxane-refractory breast cancer patients: a Southern Italy Cooperative Oncology Group phase I/II study.
We sought to define the recommended dose of cyclophosphamide (CTX) for subsequent phase II assessment when combined with fixed doses of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and 5-fluorouracil/folinic acid in metastatic breast cancer patients previously treated with anthracyclines and taxanes. Patients age 70 or less, with an Eastern Cooperative Oncology Group performance status 0 to 2, were enrolled. Patients received gemcitabine 1,000 mg/m(2), 5-fluorouracil 425 mg/m(2), folinic acid 100 mg/m(2), and escalating doses of CTX (in 100-mg/m(2) increments), starting at 500 mg/m(2), on days 1 and 8 every 3 weeks. Since March 1999, 46 patients, with a median age of 51 years (range, 38 to 74 years), entered the trial in seven cohorts. Cyclophosphamide dose escalation was stopped at 600 mg/m(2) when three of six patients experienced dose-limiting toxicity (one each with grade 3 thrombocytopenia, grade 3 neutropenia, and persistent grade 2 neutropenia), and then continued with granulocyte colony-stimulating factor support. The CTX dose of 800 mg/m(2) was proven safe and was chosen for phase II study. Two complete and 15 partial responses provided an overall response rate of 37% (95% confidence interval, 23% to 51%). Gemcitabine/CTX/5-fluorouracil/folinic acid is well tolerated by metastatic breast cancer patients pretreated with anthracyclines/taxanes, up to a CTX dose of 800 mg/m(2). The phase II study is ongoing. Semin Oncol 28 (suppl 10):50-56.
Frasci
G
G
Division of Medical Oncology, Department of Radiology, National Tumor Institute, via Mariano Semmola 80131, Naples, Italy.
D'Aiuto
G
G
Comella
P
P
Thomas
R
R
Capasso
I
I
Botti
G
G
Cortino
G R
GR
De Rosa
V
V
Comella
G
G
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel; D000093542:Gemcitabine
D000903:Antibiotics, Antineoplastic; D003841:Deoxycytidine; D003520:Cyclophosphamide; D017239:Paclitaxel; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine