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Alendronate is a potent bisphosphonate that has been studied for the treatment of osteoporosis and Paget's disease of the bone. To examine the pharmacokinetics of this drug, several groups of postmenopausal women were dosed intravenously in several studies. Twelve patients with metastatic bone disease were administered an intravenous dose of 10 mg of 14C-labeled alendronate (approximately 26 muCi), and plasma, feces, and urine samples were collected for 72 hours. Radioactivity was excreted almost exclusively in urine, and all of it was accounted for by alendronate. Overall recovery accounted for 47% of dose, with the remainder presumed to be retained in bone. Metabolism of alendronate was not observed. Renal clearance of alendronate was 71 mL/min. An additional 10 subjects were given repeated i.v. administrations of alendronate to demonstrate that previous exposure does not alter the pharmacokinetic behavior of the drug. Examination of the findings from these and other studies in which alendronate was administered intravenously revealed that disposition of single doses is linear in the range of 0.125 to 10 mg. With the possible exception of a somewhat greater skeletal retention of a systemically administered dose, the pharmacokinetics of i.v. alendronate were found to be similar to those of other bisphosphonates.

The aim of this prospective study was to evaluate biological markers, their correlation with response and outcome, and the change in these markers under the influence of preoperative chemotherapy (PCT) in patients with a large primary breast cancer. One hundred and thirty-five women were treated with PCT, followed by locoregional therapy and adjuvant treatment. Estrogen receptor (ER), progesterone receptor (PgR), HER-2, p53, and cathepsin D were determined by immunohistochemistry (IHC) before and after PCT. The overall response (OR) was 70% and the pathologic complete response (pCR) was 13%. Forty-four percent of the patients could be offered breast-conserving surgery (BCS). At a median follow-up of 50 mo the overall survival is 82% and the disease-free survival is 70%. No local recurrence (LR) has developed following BCS. Invasive ductal carcinoma (IDC) was more frequently ER-negative and HER-2-positive than invasive lobular carcinoma (ILC). P53-negative and ER-negative patients seemed to be more chemosensitive compared to p53-positive patients (74% vs 53%) and ER-positive patients (75% vs 65%), but this difference did not reach statistical significance. A trend toward higher complete pathologic remission rate was seen for ER-negative patients (p = 0.0609). PgR, HER-2, and cathepsin D were not related to response. The pattern of biological markers did not change with PCT, making repeated determination useless.

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