Know Cancer

forgot password

A Phase II Study of Weekly Low-Dose Paclitaxel Plus 24-Hour Infusion of Cisplatin as First-Line Chemotherapy for Metastatic Breast Cancer

Phase 2
18 Years
75 Years
Open (Enrolling)
Breast Neoplasms

Thank you

Trial Information

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.

Inclusion Criteria:

- 1.Women with histologically proven breast cancer and clinical evidence of distant
metastasis. (AJCC staging, 2002; see Appendix I)

- 2.Bi-dimensionally measurable disease by physical examination or image study
(roentgenogram or computed tomography (CT) scan). The index lesions should be at
least 20 mm × 20 mm in size.

- 3.Age must be older than 18 and younger than 75 year-old.

- 4.Karnofsky performance status 70%. (see Appendix)

- 5.Adequate bone marrow reserves, defined as white blood cell(WBC)4,000/l, absolute
neutrophil count (ANC) 1,500/l, platelet 100,000/l.

- 6.Liver transaminases 3 times upper normal limit if no liver metastasis and 5 times
upper normal limit if liver metastasis is present; total bilirubin 2 mg/dl;serum
creatinine 1.5 mg/dl.

- 7.No prior chemotherapy for metastatic disease. Previous chemotherapy as adjuvant
treatment is acceptable, if the adjuvant chemotherapy has been completed at least 6
months before entry into in this study.

- 8.If the patients have received hormonal therapy for metastatic disease, there must
be definite evidence of disease progression under the hormonal therapy,and hormonal
therapy should be discontinued before entry into this study.

- 9.Previous or concurrent radiotherapy is acceptable if the area of radiation does not
involve the site of the index tumor lesions.

- 10.Patients of childbearing age should have effective contraception during the study

- 11.All patients must be informed of the investigational nature of this study and must
sign and give written informed consent in accordance with institutional guidelines.

Exclusion Criteria:

- 1.Patients who are receiving concurrent hormonal or cytotoxic therapy or other
experimental therapy.Concurrent therapy with other biological agents, such as
Trastuzumab (Herceptin), is not allowed.

- 2.Patients who refuse port-A catheter implantation.

- 3.Patients who have received taxane (paclitaxel or docetaxel) or cisplatin as
adjuvant chemotherapy.

- 4.Patients with brain or leptomeningeal metastases.

- 5.Patients who have significant cardiac arrhythmia or acute myocardial infarction
within 6 months before entry.

- 6.Patients who have major systemic diseases that the attending physicians considered
inappropriate for systemic chemotherapy.

- 7.Life expectancy less than 2 months.

- 8.Pregnant or nursing patients may not participate. Patients with reproductive
potential may not participate unless they have agreed to use an effective
contraceptive method.

- 9.No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancers, in situ cervical cancer, adequately treated
stage I or II cancer from which the patient is currently in complete remission, or
any cancer from which the patient has been disease-free for 5 years.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Principal Investigator

Kun Huei Yeh, Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Far Eastern Memorial Hospital


Taiwan: Department of Health

Study ID:




Start Date:

October 2005

Completion Date:

Related Keywords:

  • Breast Neoplasms
  • Breast Neoplasms
  • Neoplasms