Phase II Trial Comparing ABI-007 (Abraxane®, Nab®-Paclitaxel) to Taxotere in First Line Therapy of Patients With Stage IV Breast Cancer

This was an open-label, randomized study to compare the following regimens with respect to toxicity and antitumor activity:

• the maximum tolerated dose (MTD) of ABI-007 300 mg/m^2 every 3 weeks;
• ABI-007 100 mg/m^2 administered weekly for 3 weeks with a 1 week rest;
• ABI-007 150 mg/m^2 administered weekly for 3 weeks with a 1 week rest;
• the standard dose and schedule of Taxotere (100 mg/m^2 every 3 weeks).

Inclusion criteria

Patients had to meet the following criteria to be eligible for the study:

• Pathologically confirmed adenocarcinoma of the breast.
• No prior chemotherapy for metastatic breast cancer.
• Stage IV disease.
• Measurable disease (must have been ≥ 2.0 cm, except for pulmonary lesions that were well documented on CT scan that were ≥ 1.0 cm).
• At least 3 weeks since prior cytotoxic chemotherapy (patients should have recovered from all acute effects of such therapy.
• At least 4 weeks since radiotherapy, with full recovery. The measurable disease was completely outside the radiation portal or there was radiologic or clinical exam proof of progressive disease within the radiation portal.
• At least 4 weeks since major surgery, with full recovery.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Age ≥18 years.
• Patient had the following blood counts at Baseline:

• Absolute neutrophil count (ANC) ≥1.5*10^9 cells/L
• Platelets ≥100*10^9 cells/L
• Hemoglobin (Hgb) ≥9 g/dL.
• Patient had the following baseline blood chemistry levels:

• Aspartate aminotransferase (AST [SGOT]), alanine aminotransferase (ALT [SGPT])≥2.5x upper limit of normal (ULN) range
• Total bilirubin normal
• Alkaline phosphatase ≥2.5x ULN (unless bone metastasis is present in the absence of liver metastasis)
• Creatinine ≥1.5 mg/dL.
• Peripheral neuropathy Grade 0 or 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
• If female of childbearing potential, pregnancy test was negative (within 72 hours of the first dose of study drug).
• If fertile, the patient agreed to use an effective method to avoid pregnancy for the duration of the study.
• Informed consent had been obtained.

Exclusion criteria

Patients who met any of the following criteria were excluded from the study:

• Prior neo-adjuvant or adjuvant chemotherapy was allowed. No prior chemotherapy for metastatic disease was allowed. If a taxane was part of the adjuvant regimen, at least one year should have transpired since completion of taxane regimen.
• Cumulative life-time dose of doxorubicin >360 mg/m^2. Doxorubicin was allowed as prior neo-adjuvant or adjuvant therapy but not for metastatic disease.
• Concurrent immunotherapy or hormonal therapy for breast cancer.
• Parenchymal brain metastases, unless documented to be clinically and radiographically stable for at least 6 months after treatment.
• Serious intercurrent medical or psychiatric illness, including serious active infection.
• History of class II-IV congestive heart failure.
• History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.
• Patients who had received an investigational drug within the previous 3 weeks.
• Patient was enrolled in a different clinical study in which investigational procedures were performed or investigational therapies were administered. Also, a patient was not permitted enroll in such clinical trials while participating in this study.
• Pregnant or nursing women
• Patients with prior hypersensitivity to either Taxol or Taxotere.