PHASE-I STUDY OF PACLITAXEL IN COMBINATION WITH CYCLOPHOSPHAMIDE AND GRANULOCYTE-COLONY-STIMULATING FACTOR IN METASTATIC BREAST-CANCER PATIENTS

Purpose: In vitro data suggest that prolonged exposure to paclitaxel e nhances breast cancer cytotoxicity. Our objective in this phase I stud y was to determine the tolerability of paclitaxel administered by 72-h our continuous intravenous (IV) infusion (CIVI) in combination with hi gh-dose cyclophosphamide and granulocyte colony-stimulating factor (G- CSF) in the ambulatory setting to metastatic breast cancer patients. P atients and Methods: Paclitaxel was administered over 72 hours by CIVI and cyclophosphamide was given daily by IV bolus on days 1,2, and 3, followed by G-CSF every 21 days. The availability of ambulatory infusi on pumps and paclitaxel-compatible tubing permitted outpatient adminis tration. Results: Fifty-five patients with metastatic breast cancer wh o had been previously treated with a median of two prior chemotherapy regimens were entered onto the study. Dose-limiting toxicity of grade 4 neutropenia for longer than 5 days and grade 4 thrombocytopenia occu rred in three of five patients treated with paclitaxel 160 mg/m(2) CIV I and cyclophosphamide 3,300 mg/m(2) followed by G-CSF. The maximum-to lerated dose (MTD) was paclitaxel 160 mg/m(2) CIVI and cyclophosphamid e 2,700 mg/m(2) in divided doses with G-CSF. Nonhematologic toxicities were moderate and included diarrhea, mucositis, and arthalgias. Altho ugh hemorrhagic cystitis developed in six patients, recurrence was pre vented with IV and oral mesna, which permitted continued outpatient de livery. One hundred seventy-four cycles were safely administered in th e ambulatory setting using infusional pumps and tubing. Objective resp onses occurred in 23 (one complete and 22 partial) of 42 patients with bidimensionally measurable disease (55%; 95% confidence interval, 38% to 70%), with a response rate of 73% (11 of 15) seen at the highest d ose levels. Conclusion: paclitaxel by 72-hour CIVI with daily cyclopho sphamide followed by G-CSF can be administered safely in the ambulator y setting, has acceptable toxicity, and is an active regimen in the tr eatment of metastatic breast cancer. (C) 1996 by American Society of C linical Oncology.