Abraxane Effective for Metastatic Breast Cancer

SAN ANTONIO, Dec. 17 -- Abraxane, the nanoparticle albumin-bound form of paclitaxel, appears effective against metastatic breast cancer in combination with Xeloda (capecitabine), according to a small study.

Among 38 patients in the phase II study, 44.1% had a partial response and 8.8% had a complete response, said Lee Schwartzberg, M.D., of the West Clinic in Memphis, in a presentation here at the San Antonio Breast Cancer Symposium.

Furthermore, the combination was well tolerated, Dr. Schwartzberg said.

Although Abraxane is approved for second-line treatment of metastatic breast cancer, there has been little or no evidence on whether the novel taxane could be combined with other chemotherapy drugs, as has been done with standard solvent-based paclitaxel, he said. The findings suggest that it can, he said.

"This dose could be as active, or more, as established doses of standard paclitaxel," Dr. Schwartzberg said.

However, phase III studies will be needed before Abraxane can be judged safe and effective in combination therapy, commented Shail Verma, M.D., of the Ottawa Cancer Center in Ottawa.

Oncologists should be cautions about untested combinations "rather than being knights in shining armor with the latest treatments," he said.

In the open-label, multicenter study, all patients received 125 mg/m² intravenous Abraxane on day one and eight along with 825 mg/m² of oral Xeloda twice daily on days one through 14 every three weeks.

Participants had received no prior chemotherapy or Xeloda for metastatic disease and no adjuvant fluorpyrimidine or paclitaxel therapy within the six months prior to baseline. None had HER2 positive disease. The average age was 58.3. Half had received prior chemotherapy for non-metastatic cancer and 39.5% had received prior radiotherapy.

The researchers reported interim results after administering 213 cycles. Of the 38 patients analyzed, 36.8% had received one to four cycles, 49.9% five to nine cycles, and 13.1% received 10 to 14 cycles. Their best responses were:

• Three patients (8.8%) had a complete response.
• 15 (44.1%) had a partial response.
• 11 (32.4%) had stable disease.
• Five (14.7%) had a progression of disease during the study.

Another four patients were not evaluable, one because of brain metastases.

Also, progression-free survival seemed to be prolonged by the regimen though the data are still preliminary, Dr. Schwartzberg said. The 25th quartile for time to progression was 133 days.

Regarding safety, the researchers reported:

• 26.3% of patients had a grade three adverse event and 7.9% had a grade four adverse event,
• There were three cases of grade three hand-foot syndrome, four grade three and one grade four cases of neutropenia, and four grade three neuropathy cases,
• For Abraxane, three patients required a dose reduction, nine had a dose held, and three had a dose delay, and
• For Xeloda, five patients had a dose reduction and five had a dose held.

The researchers concluded that the combination of Abraxane and Xeloda will need further study before it could be adopted in clinical practice.

"Based on this interim efficacy and data, a phase III trial comparing this regimen to other active combinations should be considered," Dr. Schwartzberg said.

Researchers here will also present the results of a randomized phase II trial comparing weekly and every-three-week Abraxane dosing to every-three-week Taxotere dosing as first-line therapy for metastatic breast cancer.