Clinical Experience with Tamoxifen in Advanced Breast Cancer

Abstract

The discussion on clinical experience with tamoxifen concentrated on 18 questions answered by a panel, which reached the following conclusions:

• 1) What is the Response Rate to Tamoxifen and the Duration of Response?

  When tamoxifen is used as the first method of systemic therapy in advanced breast cancer, objective evidence of tumour regression (over 50% decrease in size) occurs in about 30%—35% of cases overall, and complete regression occurs in about one-third of these cases. When it is used as secondary therapy, the objective response rate is lower — only about 20%—25%. The mean duration of response reported is 9–15 months in large series, and many of the patients on whose experience this is based were still alive at the time of the reports. Remissions of 3–4 years are not uncommon. In addition to objective regression of the tumour, a subjective response occurs in about 60% of patients treated. It includes a general feeling of well-being, increased appetite and weight, and relief of bone pain even without recalcification of bone metastases. The cause of the last observation is not known.

• 2) What is the Optimum Dosage Level for Tamoxifen in Breast Cancer?

  Pharmacokinetic mechanisms of tamoxifen in man need further investigation. Early reports suggested that 40 mg tamoxifen daily yielded a higher response rate than did 20 mg daily, but this was not confirmed in later reports. The avoidance of unnecessarily high dosage of tamoxifen — as used by some trialists — may be particularly important when it is used for long-term adjuvant therapy, and it might be advisable to adjust the dosage according to the body surface. Further clinical trials are necessary to clarify this point, and also to correlate oral intake of the drug with circulating levels in the blood. Furthermore, we need more information on how to fractionate drug dosage over the 24 h, because it appears that tamoxifen has a fairly long half-life in the blood.