Maintenance Paclitaxel Does Not Delay Progression of Metastatic Breast CancerKey Words
Breast cancer, paclitaxel (Taxol®), maintenance therapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
Women with metastatic breast cancer whose disease stopped progressing after initial chemotherapy with the drug paclitaxel (Taxol®) gained no further benefit from staying on paclitaxel, according to a phase III trial. The “maintenance” therapy patients relapsed just as frequently as those who stopped chemotherapy after their initial, successful treatment.
Source
Journal of Clinical Oncology, August 20, 2006 (see the journal abstract)
(J Clin Oncol 2006 Aug 20; 24: 3912-18)
Background
When breast cancer has spread (metastasized) to other parts of the body, treatments rarely cure the disease, but they can sometimes reduce symptoms and extend a patient’s life beyond the general median survival time of 18 to 24 months. Depending on the patient’s disease characteristics, chemotherapy is often recommended as a way to control and slow the cancer’s spread. Such therapy commonly includes a taxane, such as paclitaxel or docetaxel.
Should patients stay on chemotherapy once initial treatment has stopped the cancer’s progress? Despite inconclusive findings from previous studies, many doctors recommend such maintenance therapy in hopes of further delaying a relapse. More research is needed, however, to clarify whether the additional toxicity is worth it.
The Study
This phase III clinical trial was designed to test whether patients who responded well to first-line (initial) chemotherapy for metastatic breast cancer would benefit by continuing to take paclitaxel. Between April 1998 and October 2003, 459 women diagnosed with metastatic breast cancer were treated with paclitaxel, combined either with epirubicin or doxorubicin, for about five months.
After this initial chemotherapy treatment, 255 patients qualified for the trial because their disease had been stabilized and their cancer was no longer progressing. These patients were
randomly assigned either to continue receiving paclitaxel alone (maintenance therapy), or to be observed with no treatment until their disease recurred. Maintenance therapy consisted of a three-hour infusion once every three weeks for eight courses.
Researchers examined all patients every three months, evaluating side effects and noting when the patients’ cancer returned.
In September 2003, the study was closed early when an interim analysis of the data showed a very low likelihood of there being a benefit from maintenance paclitaxel.
The study’s principal investigator was Alessandra Gennari, M.D., Ph.D., from the National Cancer Research Institute in Genoa, Italy. The study is commonly referred to as the MANTA1 trial.
Results
Due in part to the trial’s premature closing, researchers based their final results on 215 of the 255 randomly assigned patients.
The median time to disease progression of the 109 patients receiving maintenance paclitaxel was eight months, compared to nine months for the 106 patients who were only observed, a difference that was not statistically significant. There was also no difference in the risk of death at two years: 57 percent for both groups.
The main side effect experienced by about one in three maintenance paclitaxel patients was sensory neuropathy, which can be experienced as pain, numbness, and general weakness. Paclitaxel also caused the white blood cell count to decrease in 25 of 109 patients.
A quality-of-life analysis for all patients is underway and has not yet been published.
Comments
It has become common practice to continue chemotherapy for metastatic breast cancer patients after first-line treatment works, said Jo Anne Zujewski, M.D., a breast cancer specialist with the National Cancer Institute’s Division of Cancer Treatment and Diagnosis.
“However,” she said, “the earlier trials provide no clear evidence to support that practice, and these results suggest even more strongly that patients could safely be given a ‘drug holiday’ from chemotherapy. We need to develop better therapies that are less toxic.”
Limitations
Zujewski pointed out that current paclitaxel maintenance treatments are routinely given once a week, three times more often than in this trial.
“We recognize that this may be no longer regarded as the optimal administration schedule of paclitaxel,” wrote the researchers, “[h]owever, at the time the study was designed, the decision was based on available evidence.”
Also, said Zujewski, research in this area needs to clearly define the target population. “The fact that only 55 percent of the original patients responded well enough to be randomized into maintenance treatment limits this result to patients who have a better prognosis,” she said..
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