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Key words

Metastatic breast cancer, dose-dense chemotherapy, paclitaxel (Taxol®), trastuzumab (Herceptin®). (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Summary

Weekly administration of the drug paclitaxel (Taxol®) 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. The same study found no benefit from adding the drug trastuzumab (Herceptin®) to paclitaxel for women with metastatic breast cancer whose tumors do not overproduce a protein called HER2.

Source

American Society of Clinical Oncology annual meeting, New Orleans, June 5, 2004. Final results subsequently published in the April 1, 2008, Journal of Clinical Oncology (see the journal abstract).
(J Clin Oncol. 2008 Apr 1;26(10):1642-9)

Background

Conventional cancer chemotherapy is given at three-week intervals. In recent years, however, some researchers have begun to investigate “dose-dense” drug regimens where chemotherapy drugs are given more frequently, such as once a week or once every two weeks. The drug dose is either kept the same or is lowered slightly. The idea is that exposing cancer cells to the drugs more frequently may kill more cells and thus improve the effectiveness of chemotherapy.

Previous studies have suggested that giving the drug paclitaxel (Taxol) at weekly intervals might decrease side effects while improving outcomes for women with breast cancer that has spread (metastasized) to other parts of the body.

Studies have also shown that the drug trastuzumab (Herceptin), in combination with paclitaxel, improves response rates in patients with metastatic breast cancer whose tumors overexpress (make too much of) a protein called HER2. About 25 percent of breast tumors are HER2-positive. These tumors tend to grow faster than other tumors. Trastuzumab targets the cancer cells that overexpress HER2 and slows or stops their growth.

The Study

The main goals of the study (called CALGB 9840) were to find out (1) whether more patients would respond to treatment with weekly paclitaxel than to the standard paclitaxel regimen, and (2) whether the addition of trastuzumab to paclitaxel would improve response rates in patients whose tumors did not overexpress HER2.

A total of 585 patients were enrolled. When the trial began, patients were randomly assigned to receive either weekly paclitaxel or the standard paclitaxel regimen. While the trial was underway, trastuzumab became accepted as standard therapy for patients with HER2-positive tumors. From then on, all patients with HER2-positive tumors received trastuzumab in addition to paclitaxel. Other patients were randomly assigned to receive either paclitaxel alone or trastuzumab in addition to paclitaxel.

This study was conducted by the Cancer and Leukemia Group B (CALGB), one of several cooperative groups funded by the National Cancer Institute to conduct large cancer clinical trials. The principal investigator was Andrew Seidman, M.D., of Memorial Sloan-Kettering Cancer Center in New York. (See the protocol summary.)

Results

When the researchers calculated the study’s results, they included an additional 158 patients who had been treated with the conventional three-weekly paclitaxel regimen in another CALGB study. This brought the total number of patients included in the calculation of results to 743.

Forty percent of patients treated with weekly paclitaxel responded to treatment, compared with 28 percent of those who received the standard regimen. Patients in the weekly paclitaxel group lived for nine months on average before their disease progressed. In patients receiving the standard paclitaxel regimen, by contrast, disease progressed after five months.

Among patients treated with weekly paclitaxel, there were more nervous-system side effects but fewer instances of low blood counts.

For patients with tumors that did not overproduce the HER2 protein, additional treatment with trastuzumab did not improve the response rate, a finding consistent with previous studies.

Comment

By design, the trial included in its final analysis 158 patients from another trial. These patients had received treatment similar to that given to patients who had been randomly assigned to the standard paclitaxel arm of the trial discussed here. However, some physicians at the ASCO presentation questioned whether the inclusion of patients from another trial might not have biased the final result.

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