New Form of Paclitaxel Causes Fewer Side Effects in Advanced Breast CancerKey Words
Breast cancer, paclitaxel (Taxol®), albumin, ABI-007 (Abraxane®). (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
In patients with breast cancer that had spread to other organs, a new formulation of the drug paclitaxel caused fewer side effects and delayed progression of disease for longer than the standard form of the drug. However, the study did not determine whether patients who got the new form of paclitaxel lived any longer than the other group.
Source
Journal of Clinical Oncology, published online Sept. 19, 2005, and in print Nov. 1, 2005.
Background
Paclitaxel (Taxol®) is a standard drug for the treatment of advanced breast cancer. However, paclitaxel frequently causes severe side effects, which may include a low white blood cell count, weakness, infection, and muscle pain, as well as numbness, tingling, and burning sensations in the arms and legs (neuropathy). These side effects limit the dose of the drug that can safely be given to patients.
Paclitaxel can also cause serious allergic reactions. These reactions are usually not to the drug itself but to the chemicals (solvent) used to dissolve the drug so it can enter the bloodstream (paclitaxel is hydrophobic; that is, it doesn’t dissolve in water). To prevent allergic reactions, patients must take antihistamines and corticosteroids (“premedication”) before being given paclitaxel.
ABI-007 (Abraxane®) is a new formulation of paclitaxel. Instead of using a solvent, ABI-007 binds paclitaxel to albumin, a protein found naturally in the body that transports hydrophobic molecules in the blood. In a phase II trial, patients with advanced breast cancer responded well to ABI-007 and had fewer, less severe side effects. Patients also had no allergic reactions, despite not receiving premedication to prevent them.
The Study
In this phase III trial, researchers directly compared the safety and effectiveness of ABI-007 with standard paclitaxel in patients with advanced breast cancer. The study involved 460 patients in five countries (the United States, Canada, the United Kingdom, Russia, and Ukraine).
Most of the patients had cancer that had spread to the lungs, the abdomen, or the liver. Most had had previous chemotherapy and had either never taken paclitaxel or had only received it more than a year before the current study. Patients were assigned at random to treatment every three weeks with either ABI-007 or standard paclitaxel.
Because earlier studies had shown ABI-007 to be less toxic than an equal dose of standard paclitaxel, for this trial researchers gave patients in the ABI-007 group a dose about 50 percent higher than that given to patients treated with standard paclitaxel. Standard-therapy patients received the usual premedication to avert allergic reactions, whereas those assigned to ABI-007 received no premedication.
The absence of premedication meant that patients treated with ABI-007 were able to receive each dose over the course of about 30 minutes. Doses of standard paclitaxel had to be given more slowly, with each dose taking about three hours.
The study’s lead author is William J. Gradishar, MD, of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago.
Results
Tumors disappeared or shrank to at least half their former size in 33 percent of patients treated with ABI-007, compared with 19 percent of those who received standard paclitaxel. Progression of disease was delayed for a median of 23 weeks in the ABI-007 group, compared with 16.9 weeks in the standard treatment group.
No patients in the ABI-007 group had severe allergic reactions, despite receiving a higher dose of the drug without premedication. By contrast, five patients in the standard paclitaxel group had severe allergic reactions in spite of receiving premedication.
Fewer patients treated with ABI-007 had a severe drop in their white blood cell count. However, numbness, tingling, and burning sensations in the arms and legs occurred more often in the ABI-007 group than in the standard paclitaxel group. This side effect usually diminished in severity if treatment was stopped temporarily and resumed at a lower dose.
As a result of this study and findings from earlier studies of ABI-007, the U.S. Food and Drug Administration approved the drug in January 2005 for the treatment of advanced breast cancer after other chemotherapy has been tried and is no longer working.
Limitations
“In this study, [ABI-007 ] was compared with standard paclitaxel given every three week., However, giving paclitaxel every three weeks may not be the most effective way to use the drug,” says Jo Anne Zujewski, M.D., a medical oncologist and breast cancer specialist with the National Cancer Institute’s Cancer Therapy Evaluation Program.
A more frequent dosing schedule might be more effective. In a study presented at the American Society of Clinical Oncology’s 2004 annual meeting, weekly administration of standard paclitaxel to patients with breast cancer that had spread to other parts of the body resulted in a higher response rate and a longer delay until patients’ disease progressed, compared with conventional administration of the drug every three weeks. (See Dose-Dense Chemotherapy Helped Patients with Metastatic Breast Cancer.)
In an accompanying editorial, medical oncologists Mark Harries, M.D., Paul Ellis, M.D., and Peter Harper, M.D., of Guy’s and St. Thomas’s Hospitals in London agree that it remains unclear what the best schedule of paclitaxel treatment should be. Also, they note, at least one randomized clinical trial has found another taxane drug called docetaxel to be superior to paclitaxel in the treatment of metastatic breast cancer. “Before a change in practice is considered as a result of [the current] study,” they write, more studies are needed to compare ABI-007 (alone and in combination) to docetaxel-based treatments.
Comments
Nonetheless, said Zujewski, ABI-007 is a new treatment option that may offer advantages for some patients with advanced breast cancer. The British editorialists agree, writing, “In a situation in which a single-agent three-weekly taxane is being considered for metastatic breast cancer, this trial would certainly suggest that ABI-007 could be used.”
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