Patients carrying CYP2C8*3 have shorter systemic paclitaxel exposure.

AIM: First, evaluate if patients carrying putatively diminished activity CYP2C8 genotype have longer paclitaxel exposure (e.g., time above threshold concentration of 0.05 µM [Tc >0.05]). Second, screen additional pharmacogenes for associations with Tc >0.05. Methods: Pharmacogene panel genotypes were translated into genetic phenotypes for associations with Tc >0.05 (n = 58). RESULTS: Patients with predicted low-activity CYP2C8 had shorter Tc >0.05 after adjustment for age, body surface area and race (9.65 vs 11.03 hrs, ß = 5.47, p = 0.02). This association was attributed to CYP2C8*3 (p = 0.006), not CYP2C8*4 (p = 0.58). Patients with predicted low-activity SLCO1B1 had longer Tc >0.05 (12.12 vs 10.15 hrs, ß = 0.85, p = 0.012). CONCLUSION: Contrary to previous publications, CYP2C8*3 may confer increased paclitaxel metabolic activity. SLCO1B1 and CYP2C8 genotype may explain some paclitaxel pharmacokinetic variability.

Intravenous bisphosphonate therapy does not acutely alter nuclear bone scan results.

INTRODUCTION: Theoretically, the bisphosphonates used to treat metastatic bone disease could influence the results of nuclear bone scans which use the structurally similar technetium 99m methylene diphosphonate (99mTc MDP). A prospective clinical study was designed to explore this hypothesis. PATIENTS AND METHODS: Patients with metastatic breast cancer receiving intravenous bisphosphonate (IVBP) therapy who had > or =3 osseous lesions on nuclear bone scan were eligible. A baseline bone scan (number 1) was performed as clinically indicated and IVBP with zoledronic acid was administered within 72 hours. A second bone scan (number 2) was performed within 72 hours of zoledronic acid dosing. Both bone scans were reviewed in a blinded fashion and assessed for changes in the number and intensity of osseous lesions. Ten patients were planned to yield at least 30 lesions. RESULTS: Ten patients were enrolled. One patient withdrew consent and 1 was excluded due to protocol deviation. Among the 8 patients were 163 assessable osseous lesions. The median time from bone scan number 1 to IVBP was 1 day (range, 1-2 days). The median time from IVBP to bone scan number 2 was 2 days (range, 1-3 days). The paired imaging showed no changes in the total number of bone metastases. One hundred sixty-one lesions were identical in both scans; in 1 patient there were 2 lesions that were discordant, one more intense, the other less intense. CONCLUSION: These data do not support the hypothesis that IVBP therapy interferes with bone scan results.

Markers of bone metabolism in women receiving aromatase inhibitors for early-stage breast cancer.

The aromatase inhibitors have been widely incorporated into the adjuvant breast cancer care of postmenopausal women with estrogen and/or progesterone receptor-positive breast cancer. Aromatase inhibitor use is associated with an increased risk of lowering bone mineral density and accelerating the risk of fragility fractures. Optimizing bone health includes appropriate nutrition and exercise, as well as screening for and treatment of low bone mass. Assessment of an individual's risk of fracture typically includes measuring the bone mineral density and other clinical risk factors, and there are evolving data as to the potential added information obtained by measuring biochemical markers of bone metabolism.

Third North American Symposium on Skeletal Complications of Malignancy: summary of the scientific sessions.

The current introduction summarizes the five scientific sessions (bone marrow microenvironment and animal models of bone metastasis; prostate carcinoma; multiple myeloma; breast carcinoma; and preclinical and clinical studies on metastasis: future directions) and provides an overview of the proceedings of the Third North American Symposium on Skeletal Complications of Malignancy, Bethesda, Maryland, April 25-27, 2002.