Efficacy of pamidronate in breast cancer with bone metastases: a randomized, double-blind placebo-controlled multicenter study.

PURPOSE: To evaluate the efficacy of pamidronate 60 mg i.v. q 4 weeks in women with advanced breast cancer with skeletal metastases. PATIENTS AND METHODS: 404 woman with skeletal metastases from breast cancer in Sweden and Norway were included in a randomized, placebo-controlled, multicenter study. Except for the study medication, other palliative treatment was chosen at the discretion of the physician. Skeletal related events, i.e. increased pain, treatment of hypercalcemia, pathologic fractures of long bones or pelvis, paralyses due to vertebral compression, palliative radiotherapy for skeletal metastases, surgery on bone and change of antitumor therapy were recorded every third month as well as a self-estimated pain-score using visual Analog Scales and analgesic consumption. RESULTS: There was a significantly increased time to progression of pain (p < 0.01), to hypercalcemic events (p < 0.05) as well as for the cumulative number of skeletal related events (p < 0.01) in favor for the pamidronate group. No statistically significant reduction of pathologic fractures of long bones or pelvis, or pareses due to vertebral compression occurred. No statistically significant differences were found for the need of radiotherapy and surgery on bone. The pamidronate group faired better regarding performance status (p < 0.05). There was a statistically not significant lower consumption of opioid analgesics in the pamidronate group (p = 0.14). CONCLUSION: Pamidronate 60 mg i.v. q 4 weeks reduces skeletal events and improves the quality of life in women with bone metastases from breast cancer.

Influence of tranexamic acid on tumour blood flow.

The influence on the intratumour blood flow distribution in a transplantable rat sarcoma by a potent antifibrinolytic drug, tranexamic acid, administered intraperitoneally for 3 or 10 days was studied by the intratumour distribution of intravenously injected 86Rb. A local Xenon clearance technique was used to study the direct effect of tranexamic acid on local tumour blood flow. local tumour blood flow and the intratumour blood flow distribution after administration of tranexamic acid for 3 days were unchanged compared to controls. Prolonged administration of tranexamic acid changed the intratumour blood flow distribution significantly towards low flow values. This might be one mechanism behind the inhibiting effect of tranexamic acid in tumour growth rate, previously observed in both experimental and clinical studies.

Influence of tranexamic acid on tumour vascularization. An experimental microangiographic study.

Administration of tranexamic acid given from tumour transplantation up to sacrifice 5 days later, inhibited the early vascularization of an intramuscularly transplanted rat sarcoma. A marked reduction of angiographically demonstrated vascular connections between tumour and normal muscle was observed. In older, larger tumours an increased frequency of small non-vascularized and probably necrotic tumour areas was suggested after administration of tranexamic acid. An inhibiting effect of tranexamic acid on tumour growth rate has been earlier reported in both experimental and clinical studies. This effect may be explained by an influence of tranexamic acid on tumour vascularization.

Inhibition of tumour vascularization by tranexamic acid. Experimental studies on possible mechanisms.

The vascularization of an intramuscularly transplanted rat sarcoma was studied by microangiography. Administration of tranexamic acid as well as of indomethacin reduced the vascular connections between tumour and surrounding normal muscle. These drugs also reduced tumour growth rate irrespective of whether they were administered early or late during tumour growth. An electron microscopy study of tumour specimens from animals given tranexamic acid did not reveal any degenerative vascular changes. One explanation of the inhibition of tumour growth and vascularization by tranexamic acid and by indomethacin may be reduction of a local inflammatory reaction induced by tumour transplantation and stimulating tumour vascularization.