Phase I study of docetaxel and cyclophosphamide in patients with advanced or recurrent breast cancer.
BACKGROUND
A phase I clinical study of combination chemotherapy with docetaxel and cyclophosphamide (CPA) was performed to determine the maximum tolerated dose (MTD), the incidence and severity of toxicities and the pharmacokinetics in patients with advanced or recurrent breast cancer.


METHODS
Docetaxel was administered by intravenous drip infusion over 60 minutes, followed by intravenous bolus injection of CPA every 3-4 weeks. The dosage of docetaxel/CPA was 40/200, 40/400, 50/400, or 60/400 mg/m(2)/day.


RESULTS
Fifteen patients were enrolled and received a total of 33 cycles of the combined therapy. The dose limiting toxicities (DLTs) were leukopenia, neutropenia and thrombocytopenia. The MTD was estimated to be docetaxel 60 mg/m(2) in combination with CPA 400 mg/m(2) per day. Plasma clearance of both drugs was similar regardless of dose. The recommended doses of docetaxel/CPA for a phase Utrial are 50/400 mg/m(2)/day every 3-4 weeks.


CONCLUSIONS
The MTD of this combined therapy was docetaxel 60 mg/m(2) and CPA 400 mg/m(2). Neutropenia and leukopeina were common and severe. It is important to stress the need for modification of the dosing scheme.
Department of Surgery, Tokyo Women's Medical University Daini Hospital, 2-1-10 Nishiogu, Arakawa-ku, Tokyo 116-8567, Japan. shimitsu@dnh.twmu.ac.jp
Tadao
T
Shimizu
Kohji
K
Enomoto
Shunsuke
S
Haga
Mamoru
M
Fukuda
Yuichi
Y
Iino
Tadashi
T
Ikeda
Tetsuo
T
Taguchi
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000493:pharmacokinetics / Q000633:toxicity*; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity*; D043823:Taxoids
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D003520:Cyclophosphamide; D017239:Paclitaxel