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Key Words

Breast cancer, taxanes, anthracyclines. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ³.)

Summary

Combined data from eleven clinical trials showed that patients receiving taxanes (paclitaxel or docetaxel) for the treatment of newly diagnosed advanced breast cancer lived about as long as those receiving anthracyclines (epirubicin or doxorubicin). As single-agents, however, the anthracyclines offered better progression-free survival. Combinations based on taxanes provided better response rates and also better progression-free survival than those based on anthracyclines.

Source

Journal of Clinical Oncology, April 20, 2008 (see the journal abstract ⁴).
(J Clin Oncol. 2008 Apr 20; 26(12): 1980-86)

Background

In women with advanced breast cancer, the disease has spread (metastasized) to other parts of the body. Treatment rarely cures these patients but can sometimes reduce symptoms and extend life beyond the 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, and to relieve other symptoms.

For a long time, most advanced breast cancer chemotherapy included drugs from the anthracycline family, such as doxorubicin (Adriamycin®) and epirubicin (Ellence®). Then during the 1990s, members of a family of drugs called the taxanes – which include docetaxel (Taxotere®) and paclitaxel (Taxol®) – were shown to be effective in the first-line (initial) treatment of advanced breast cancer as well as in the treatment of women who had developed resistance to the anthracyclines.

Taxanes are more expensive and may have more side effects. Anthracyclines can also have significant side effects in some women, including heart damage and secondary leukemia. So which kind of drug is better for women newly diagnosed with advanced breast cancer? Should the drugs be used in combination or are they more effective when given as single agents? The following combined analysis of 11 clinical trials involving nearly 4,000 patients attempted to address such questions.

The Study

Investigators from Europe and North America combined data (called a meta-analysis) from eleven prospective clinical trials testing taxanes against anthracyclines in the first-line treatment of advanced breast cancer.

They found these eleven trials by searching databases of the medical literature (for studies that had stopped accepting patients by the end of 2001) and by reviewing conference proceedings from breast cancer and oncology meetings.

The three single-agent trials tested either paclitaxel or docetaxel (taxanes) against doxorubicin (an anthracycline). The other trials compared various taxane- and anthracycline-based combinations.

The study’s lead author is Martine J. Piccart-Gebhart, M.D., Ph.D., from the Jules Bordet Institute in Brussels, Belgium.

Results

Available for analysis were 919 patients from the three single-agent studies, and 3,034 patients from the eight studies testing various drug combinations. As a single agent, doxorubicin was better than paclitaxel in one trial only; however, paclitaxel in that study was not given every week, which has since become standard treatment. When that trial is excluded, there was no difference in survival across all of the remaining studies that compared single agents.

For drug combinations, the taxanes were eight percent more effective against tumor progression than combinations using anthracyclines; women receiving this advantage did not live longer, however. Women taking the taxane combinations were 27 percent more likely to see their tumors respond to treatment, which reduced some symptoms but did not extend those women’s lives.

While some previous studies have suggested that certain subgroups of patients might benefit more from taxanes versus anthracyclines, this meta-analysis did not reach that conclusion. There were no significant differences between patients whose disease was estrogen receptor-negative or positive, and also no differences in patients whose cancer had spread to certain other regions of the body (visceral disease).

Limitations

Pooling the results of numerous trials can provide researchers with only a “big picture” look at an issue. Individual differences – both in patient populations and how the trials are designed – tend to average out. The authors concede their results are “modest” and emphasize the need for more clinical trials that seek to identify which treatments work best for particular subgroups of breast cancer patients.

Comments

Cancer researchers most often use clinical trials to see whether a particular drug or type of treatment will make patients live longer. However, said JoAnne Zujewski, M.D., who oversees breast cancer trials for the National Cancer Institute’s Cancer Therapy Evaluation Program, “thousands of women have benefited from [the drugs included in the meta-analysis]. Controlling symptoms is an important part of treating advanced breast cancer.”

She noted that cancer patients undergoing chemotherapy treatments have different lifestyles and different attitudes about side effects. “This is why patients need to make individual choices with their treating physicians,” she explained. “These results assure doctors and patients that they can consider side effects, convenience, and cost in deciding whether to use taxanes.”

“The fact that we generally can’t cure advanced breast cancer does not nullify the findings that these drugs both have some beneficial effects, and provide patients options in terms of the quality of their survival and the intensity of their treatment,” said Zujewski. “It is vital that patients learn about and discuss these issues with their physician.”

Glossary Terms

A type of antibiotic that comes from certain types of Streptomyces bacteria. Anthracyclines are used to treat many types of cancer. Anthracyclines damage the DNA in cancer cells, causing them to die. Daunorubicin, doxorubicin, and epirubicin are anthracyclines.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

A drug used together with other drugs to treat certain types of breast cancer, stomach cancer, prostate cancer, and certain types of head and neck cancer. It is also being studied in the treatment of other types of cancer. Docetaxel is a type of mitotic inhibitor. Also called Taxotere.

A drug that is used to treat many types of cancer and is being studied in the treatment of other types of cancer. Doxorubicin comes from the bacterium Streptomyces peucetius. It damages DNA and may kill cancer cells. It is a type of anthracycline antitumor antibiotic. Also called Adriamycin PFS, Adriamycin RDF, doxorubicin hydrochloride, hydroxydaunorubicin, and Rubex.

A drug used together with other drugs to treat early breast cancer that has spread to lymph nodes. It is also being studied in the treatment of other types of cancer. Epirubicin is a type of anthracycline antibiotic. Also called Ellence and epirubicin hydrochloride.

A protein found inside the cells of the female reproductive tissue, some other types of tissue, and some cancer cells. The hormone estrogen will bind to the receptors inside the cells and may cause the cells to grow. Also called ER.

The time from either diagnosis or treatment at which half of the patients with a given disease are found to be, or expected to be, still alive. In a clinical trial, median survival time is one way to measure how effective a treatment is. Also called median overall survival and median survival.

A drug used to treat breast cancer, ovarian cancer, and AIDS-related Kaposi sarcoma. It is also used together with another drug to treat non-small cell lung cancer. Paclitaxel is also being studied in the treatment of other types of cancer. It blocks cell growth by stopping cell division and may kill cancer cells. It is a type of antimitotic agent. Also called Taxol.

The length of time during and after treatment in which a patient is living with a disease that does not get worse. Progression-free survival may be used in a clinical study or trial to help find out how well a new treatment works. Also called PFS.

In medicine, a study or clinical trial in which participants are identified and then followed forward in time.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called best practice and standard of care.

A type of drug that blocks cell growth by stopping mitosis (cell division). Taxanes interfere with microtubules (cellular structures that help move chromosomes during mitosis). They are used to treat cancer. A taxane is a type of mitotic inhibitor and antimicrotubule agent.

Having to do with the viscera, which are the soft internal organs of the body, including the lungs, the heart, and the organs of the digestive, excretory, reproductive, and circulatory systems.