A Phase II Study of Weekly Low-Dose Paclitaxel Plus 24-Hour Infusion of Cisplatin as First-Line Chemotherapy for Metastatic Breast Cancer
Breast cancer is one of the leading causes of cancer death for women in Taiwan. We have
recently demonstrated that combination of paclitaxel and cisplatin, at conventional doses,
is highly effective in the treatment of breast cancer. However, the acute and cumulative
toxicities of paclitaxel have been troublesome to a significant portion of the patients.
Several lines of evidence suggested that weekly paclitaxel, at a much lower dose range of 40
to 50 mg/m2 per week, may be as effective as that of the conventional doses of paclitaxel
(80 to 90 mg/m2 per week) for patients with metastatic ovarian and lung cancers. The
low-dose regimen of paclitaxel may significantly improve the compliance of the patients.
This open-label phase II trial is designed to test this hypothesis.
The eligibility criteria include (1) women with metastatic breast cancer; (2) measurable
disease; (3) acceptable organ function reserves. The ineligibility criteria include (1)
brain or leptomeningeal metastases; (2) previous chemotherapy for metastatic breast cancer.
The study consists of two stages. All eligible patients will receive stage I (low-dose)
regimen: paclitaxel, 50 mg/m2 1-hour iv infusion on days 1, 8 and 15, and cisplatin, 40
mg/m2 24-hour iv infusion on days 1 and 8. The treatment cycle will be repeated every 4
weeks. The first tumor response assessment will be done after 2 cycles of protocol
treatment. Patients with complete response (CR) will receive at least 2 more cycles of
low-dose regimen after documentation of CR. Patients with partial response (PR) and patients
with stable disease (SD) who have minor tumor response or improvement of general condition
will continue to receive the low-dose regimen. Patients with SD but no evident clinical
benefit and patients with progressive disease (PD) will be shifted to stage II
(conventional-dose) regimen: paclitaxel, 80 mg/m2 1-hour intravenous infusion on days 1, 8
and 15, and cisplatin, 40 mg/m2 24-hour intravenous infusion on days 1 and 8, every 4 weeks.
Tumor assessment will then be evaluated after every 2 cycles of protocol treatment. For
patients who continue low-dose regimen, those with CR will receive at least 2 more cycles of
protocol treatment. Patients with a maximal response of PR or SD may either continue the
low-dose regimen until PD or prohibitive toxicity develops or change to the
conventional-dose regimen, at the discretion of the attending physicians. Patients with PD
should change to the conventional-dose regimen. For patients who have shifted to
conventional-dose regimen, those with CR will receive at least 2 more cycles of protocol
treatment. Patients with PR will continue protocol treatment until disease progresses or
prohibitive toxicity develops. Patients with SD may continue protocol treatment or change to
salvage therapy. Patients with PD should stop protocol treatment and change to salvage
The primary endpoint of this phase II trial is the objective response rate of the stage I
(low-dose) regimen. The secondary endpoints include treatment-related toxicity, the change
in quality of life, progression free survival and overall survival. Simon's optimal
two-stage design will be used to determine the patient number. If 4 or more objective
responses (CR+PR) are documented in the first 13 patients, the study will go on to the
second stage to enroll a total of 43 patients. The P0, P1,are 20%, 40%, 0.05, and 0.2,
respectively. Assuming a dropout rate of 10%, 15 patients will be accrued in the first
stage and 33 in the second stage. Estimated time for patient accrual is 3 years.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary objective is to determine the tumor response of weekly low-dose paclitaxel plus 24-hour infusion of cisplatin chemotherapy for patients with metastatic breast cancer.
Kun Huei Yeh, Ph.D.
Far Eastern Memorial Hospital
Taiwan: Department of Health