STUDIES CONFIRM INCREASED SURVIVAL FOR BREAST CANCER PATIENTS TREATED WITH NOLVADEX.

WILMINGTON, Del.--(HealthWire)--April 18, 1995--Women treated with Nolvadex(R) (tamoxifen citrate) following surgery for breast cancer live significantly longer than those who do not receive the drug, according to several clinical trials. Survival is extended whether their cancer is estrogen-receptor (ER) positive or negative and whether or not it has spread beyond the breast to the underarm lymph nodes.

Since its introduction in the United States in 1978, Nolvadex, marketed by Zeneca Pharmaceuticals, has become the world's most prescribed and most studied anticancer medicine.(1) Its efficacy and safety profile in the treatment of breast cancer (Note A) have been established during more than 7 million patient-years of use in more than 110 countries.

As long-term results of clinical trials continue to confirm the benefits of Nolvadex therapy, patients treated with the medication can feel increasingly confident in their battle against breast cancer. "Breast cancer patients often live in fear that their disease will recur," said Paul Plourde, M.D., Senior Director of Clinical Research, Zeneca Pharmaceuticals. "Nolvadex delays recurrence, prevents the development of new primary breast cancers, and also prolongs patients' lives."

The most important publication was a meta-analysis of 40 published clinical trials of adjuvant therapy with Nolvadex, involving 30,000 women with breast cancer who were followed up for 10 years.(2) Compared with women who did not receive the medication, Nolvadex reduced the risk of death by 17% per year among node-negative patients and 18% annually among node-positive patients. The statistically significant overall survival benefit increased steadily with the length of follow-up.

One clinical trial demonstrating increased overall survival with Nolvadex is the widely reported US National Cancer Institute's NSABP B-14 study. In this trial, data from 2,844 node-negative, ER-positive breast cancer patients showed that therapy with adjuvant Nolvadex for 5 years significantly prolongs overall survival, compared with placebo. Treatment benefits were seen in both premenopausal and postmenopausal patients (p = 0.01).(3)

A second trial, conducted in Scotland, compared Nolvadex treatment started immediately after surgery and continued for 5 years (661 patients) with treatment begun at the first recurrence of breast cancer (651 patients).(4) By 8 years after surgery, a greater percentage of women given immediate Nolvadex therapy were still alive (p = 0.002). This benefit extended to both premenopausal and postmenopausal women. In addition, the Scottish Trial, the NSABP B-14 trial, and the meta-analysis showed that Nolvadex significantly delayed recurrence of breast cancer.

The large meta-analysis looked at clinical trials in which Nolvadex therapy was given to breast cancer patients for less than 2 years, 2 years, or more than 2 years. According to the authors of the report, "Indirect randomized comparisons ... show that long-term tamoxifen (eg, 2 years, or even 5 years) is significantly more effective than shorter tamoxifen regimens."(2) Nolvadex therapy appears to provide the greatest benefit in node-positive, ER-positive patients and is not indicated for premenopausal node-positive patients.

Adverse reactions to Nolvadex are relatively mild and infrequently severe enough to require discontinuation of treatment.(6) In recent trials, fewer than 5% of patients have been reported as discontinuing therapy because of side effects.(7)

The most frequently reported adverse reactions are hot flashes, vaginal discharge, and irregular menses. Deep vein thrombosis and pulmonary embolism, although uncommon, occur more frequently with Nolvadex than with placebo (0.8% vs 0.3% and 0.4% vs 0.1%, respectively).(6)

An increased risk of changes in the endometrium (lining of the uterus), including endometrial cancer, has been associated with Nolvadex treatment.(8) All women with breast cancer should have annual gynecological examinations. In addition, patients receiving Nolvadex should have routine gynecological care, and they should promptly inform their physician if they experience any menstrual irregularities, abnormal vaginal bleeding, changes in vaginal discharge, or pelvic pain or pressure. As women enter menopause, their risk of osteoporosis and heart disease usually increases. Fortunately, Nolvadex therapy is not likely to further increase these risks, as it is not associated with adverse effects on bone mineral density(9) or serum lipid profiles(10) in postmenopausal women.

Zeneca Pharmaceuticals is a business unit of Zeneca Inc. In the United States, Zeneca Inc. is a $2.5 billion bioscience company with 7,500 employees and 45 manufacturing and research and development sites in 29 states. Zeneca Inc. is a wholly owned subsidiary of the UK-based Zeneca Group PLC (NYSE: ZEN), a major $6.9 billion international bioscience business. -0- Note A: Full Nolvadex prescribing information is available upon request. -0-

References

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Exp Biol Med. In press.

2. Early Breast Cancer Trialists' Collaborative Group. Systemic

treatment of early breast cancer by hormonal, cytotoxic,

or immune therapy. Lancet. 1992;339:1-15, 71-85.

3. Fisher B, Costantino J, Redmond C, et al. Recent information from

current NSABP trials of adjuvant therapy for breast cancer. In:

Salmon SE, ed. Adjuvant Therapy of Cancer VII. Philadelphia:

JB Lippincott Co; 1993:148-161.

4. Breast Cancer Trials Committee, Scottish Cancer Trials Office.

Adjuvant tamoxifen in the management of operable breast cancer:

the Scottish Trial. Lancet. 1987;I:171-175.

5. Fisher B, Redmond C, et al for the National Surgical Adjuvant Breast

and Bowel Project. Systemic therapy in node-negative patients:

updated findings from NSABP clinical trials. J Natl Cancer Inst

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breast cancer who have estrogen-positive tumors. N Engl J Med.

1989;320:479-484.

7. Love RR. Tamoxifen therapy in primary breast cancer: biology,

efficacy, and side effects. J Clin Oncol. 1989;7:803-815.

8. Fisher B, Costantino JP, Redmond CK, et al. Endometrial cancer in

tamoxifen-treated breast cancer patients: findings from the

National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14.

J Natl Cancer Inst. 1994;86;527-537.

9. Love RR, Barden HS, Mazess RB, Epstein S, Chappell RJ. Effect of

tamoxifen on lumbar spine bone mineral density in postmenopausal

women after 5 years. Arch Intern Med. 1994;154:2585-2588.

10. Love RR, Wiebe DA, Feyzi JM, Newcomb PA, Chappell RJ. Effects of

tamoxifen on cardiovascular risk factors in postmenopausal women

after five years. J Natl Cancer Inst. 1994;86:1534-1539.

CONTACT: Karen L. Miller

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