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Key Words

Breast cancer, paclitaxel (Taxol®), docetaxel (Taxotere®). (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ³.)

Summary

In a study comparing different dosing schedules of two common breast cancer drugs, weekly treatment with the drug paclitaxel (Taxol) in addition to standard chemotherapy proved most effective in extending overall survival and disease-free survival among women with early-stage breast cancer. Treatment with the drug docetaxel (Taxotere) every three weeks improved patients’ disease-free survival and is also an acceptable choice.

Source

New England Journal of Medicine, April 17, 2008 (see the journal abstract ⁴)
(N Engl J Med. 2008 Apr 17;358(16):1663-71)

Background

Women with early-stage breast cancer have a lower risk of cancer recurrence and a better chance of survival when they are treated with chemotherapy in addition to surgery (adjuvant chemotherapy). Previous studies have shown that the risk of a recurrence is further reduced when patients receive a drug from a class known as taxanes (docetaxel or paclitaxel) in addition to the standard drugs doxorubicin and cyclophosphamide.

Questions have persisted, however, about whether one taxane is superior to the other and whether outcomes for patients treated with paclitaxel are better when the drug is given once a week instead of on a conventional once-every-three-weeks schedule.

The Study

This phase III study involved 4,950 women with breast cancer that was considered at high risk of recurrence, either because the tumor was at least two centimeters in size or because the cancer had already spread to lymph nodes in the armpit. All of the women had had either a mastectomy or lumpectomy and some had also had radiation therapy. Those whose tumors were sensitive to the hormones estrogen or progesterone also took an antihormonal drug (tamoxifen or an aromatase inhibitor) for five years.

After completing chemotherapy with doxorubicin and cyclophosphamide, the women were randomly assigned to one of four groups.

• One group received paclitaxel every three weeks (standard treatment)
• A second group received docetaxel every three weeks
• A third group received paclitaxel once a week
• A fourth group received docetaxel once a week

The study was coordinated by the Eastern Cooperative Oncology Group, a National Cancer Institute (NCI) sponsored clinical trials cooperative group (see the protocol summary ⁵). Three other NCI-sponsored cooperative groups (the Southwest Oncology Group, the Cancer and Leukemia Group B, and the North Central Cancer Treatment Group) also participated. The principal investigator was Joseph A. Sparano, M.D., of Montefiore Medical Center in New York City.

Results

The patients were followed for a median follow-up period of just over five years. When the researchers compared outcomes for women treated with paclitaxel vs. docetaxel and those treated weekly vs. every three weeks, they found no significant differences. However, when they broke out the four treatment groups and compared them, they did find differences.

Compared with women who received standard, once-every-three-weeks paclitaxel, those who received docetaxel every three weeks had better disease-free survival (that is, cancer recurrence was delayed for longer) as did those who received weekly paclitaxel. However, women in the weekly paclitaxel group also lived longer overall.

Rates of treatment side effects differed in the four treatment groups. Women who received docetaxel every three weeks had the highest rates of low white blood cell counts, which can cause complications such as infection and fever. Women treated with weekly paclitaxel had more pain, numbness, tingling, swelling, or muscle weakness in the arms and legs than patients in any other treatment group.

Comments

“This study addresses several very practical, important questions about taxane choice, dose, and treatment schedule for patients with early breast cancer,” comments Jo Anne Zujewski, M.D., head of Breast Cancer Therapeutics in NCI’s Division of Cancer Treatment and Diagnosis.

“Weekly paclitaxel showed a survival advantage, but docetaxel given every three weeks could also be an acceptable choice - for example, if weekly treatment is impractical because of the need to travel or take time off from work, or if an individual patient tolerates docetaxel better. One of the interesting things about this study is that it shows that not all taxanes are alike.”

Glossary Terms

Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, or biological therapy.

A drug that prevents the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibitors are used as a type of hormone therapy for postmenopausal women who have hormone-dependent breast cancer.

An anticancer drug that belongs to the family of drugs called alkylating agents.

The length of time after treatment for a specific disease during which a patient survives with no sign of the disease. Disease-free survival may be used in a clinical study or trial to help measure how well a new treatment works.

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 (the molecules inside cells that carry genetic information) and stops cells from growing. Rapidly growing tumor cells that take up doxorubicin may die. It is a type of anthracycline antitumor antibiotic. Also called doxorubicin hydrochloride, Adriamycin PFS, Adriamycin RDF, and Rubex.

A type of hormone made by the body that helps develop and maintain female sex characteristics and the growth of long bones. Estrogens can also be made in the laboratory. They may be used as a type of birth control and to treat symptoms of menopause, menstrual disorders, osteoporosis, and other conditions.

Surgery to remove the tumor and a small amount of normal tissue around it.

A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Lymph nodes filter lymph (lymphatic fluid), and they store lymphocytes (white blood cells). They are located along lymphatic vessels. Also called lymph gland.

Surgery to remove the breast (or as much of the breast tissue as possible).

A statistics term. The middle value in a set of measurements.

The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. The overall survival rate is often stated as a five-year survival rate, which is the percentage of people in a study or treatment group who are alive five years after diagnosis or treatment. Also called survival rate.

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 is a type of mitotic inhibitor. Also called Taxol.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

A type of hormone made by the body that plays a role in the menstrual cycle and pregnancy. Progesterone can also be made in the laboratory. It may be used as a type of birth control and to treat menstrual disorders, infertility, symptoms of menopause, and other conditions.

In statistics, describes a mathematical measure of difference between groups. The difference is said to be significant if it is greater than what might be expected to happen by chance alone. Also called statistically significant.

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 standard of care or best practice.

A drug used to treat certain types of breast cancer in women and men. It is also used to prevent breast cancer in women who have had ductal carcinoma in situ (abnormal cells in the ducts of the breast) and are at a high risk of developing breast cancer. Tamoxifen is also being studied in the treatment of other types of cancer. It blocks the effects of the hormone estrogen in the breast. Tamoxifen is a type of antiestrogen. Also called tamoxifen citrate and Nolvadex.

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.

Refers to a blood cell that does not contain hemoglobin. White blood cells include lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. These cells are made by bone marrow and help the body fight infections and other diseases. Also called WBC.