The Effect of Undaria pinnatifida Fucoidan on the Pharmacokinetics of Letrozole and Tamoxifen in Patients With Breast Cancer.

BACKGROUND: Although the use of complementary and alternative medicines is widespread in cancer patients, clinical evidence of their benefits is sparse. Furthermore, while they are often assumed to be safe with regard to concurrent use of anticancer therapies, few studies have been carried out to investigate possible interactions. Fucoidans are a group of sulfated carbohydrates, derived from marine brown algae, which have long been used as dietary supplements due to their reported medicinal properties, including anticancer activity. The aim of this study was to investigate the effect of co-administration of fucoidan, derived from Undaria pinnatifida, on the pharmacokinetics of 2 commonly used hormonal therapies, letrozole and tamoxifen, in patients with breast cancer. METHODS: This was an open label non-crossover study in patients with active malignancy taking letrozole or tamoxifen (n = 10 for each group). Patients took oral fucoidan, given in the form of Maritech extract, for a 3-week period (500 mg twice daily). Trough plasma concentrations of letrozole, tamoxifen, 4-hydroxytamoxifen, and endoxifen were measured using HPLC-CAD (high-performance liquid chromatography charged aerosol detector), at baseline and after concomitant administration with fucoidan. RESULTS: No significant changes in steady-state plasma concentrations of letrozole, tamoxifen, or tamoxifen metabolites were detected after co-administration with fucoidan. In addition, no adverse effects of fucoidan were reported, and toxicity monitoring showed no significant differences in all parameters measured over the study period. CONCLUSIONS: Administration of Undaria pinnatifida fucoidan had no significant effect on the steady-state trough concentrations of letrozole or tamoxifen and was well tolerated. These results suggest that fucoidan in the studied form and dosage could be taken concomitantly with letrozole and tamoxifen without the risk of clinically significant interactions.

Tamoxifen, soy, and lifestyle factors in Asian American women with breast cancer.

PURPOSE: Soy foods have been a staple in Asia for centuries but the consumption of this food in the West is recent. Intake of soy among women at high risk for or with breast cancer has become a public health concern because genistein, a major component of soy, has weak estrogenic effects on breast epithelium, and has been found to negate the benefit of tamoxifen in some animal and in vitro studies. PATIENTS AND METHODS: We conducted a cross-sectional study in Asian Americans with breast cancer who were tamoxifen users (n = 380) to investigate the association between soy intake and circulating levels of tamoxifen and its metabolites (N-desmethyl tamoxifen [N-DMT], 4-hydroxytamoxifen [4-OHT], and 4-hydroxy-N-desmethyl-tamoxifen [endoxifen]). RESULTS: Serum levels of tamoxifen or its metabolites were unrelated to self-reported intake of soy or serum levels of isoflavones. Blood levels of tamoxifen were 81% higher in postmenopausal women age 65 or older compared with premenopausal women age 45 or younger (P = .005); similar patterns of results were observed for the tamoxifen metabolites. Levels of N-DMT were 27% (P = .03) lower among women in the highest tertile of body mass index (BMI, > 24.4 kg/m2) compared with those in the lowest category (BMI 21.5). Women who used hypertensive medications had higher levels of tamoxifen (P = .02) and N-DMT (P = .04) compared with nonusers. CONCLUSION: We found no evidence that soy intake adversely affected levels of tamoxifen or its metabolites. However, age, menopausal status, BMI, and use of hypertensive medications significantly influenced circulating levels of tamoxifen and its metabolites in this population.

Phase I trial of 1alpha-hydroxyvitamin d(2) in patients with hormone refractory prostate cancer.

This Phase I study of 1alpha-hydroxyvitamin D(2), an p.o. administered vitamin D analogue, in patients with advanced hormone-refractory prostate cancer was designed to assess the toxicity, pharmacokinetic and biological markers of drug activity, and lastly tumor response data to recommend a dose for Phase II studies. 1alpha-Hydroxyvitamin D(2) was administered daily at doses ranging from 5 to 15 microg/day. Patients were monitored for toxicity and tumor response, and blood and urine samples were collected for pharmacokinetics (1alpha,25-dihydroxyvitamin D(2) levels) and other parameters of biological activity (bone markers, parathyroid hormone, urine calcium, and serum phosphorus levels). Twenty-five patients were enrolled. Main toxicities were hypercalcemia with associated renal insufficiency. No other significant toxicity was seen. Pharmacokinetics showed an increase in the active metabolite 1alpha,25-dihydroxyvitamin D(2) that reached a plateau by week 4 despite continuous drug dosing. Elevation in daily urinary calcium excretion and serum phosphorus levels was seen, whereas a decrease in serum parathyroid hormone was evident. Two patients showed evidence of a partial response, whereas 5 others achieved disease stabilization for > or =6 months. 1alpha-Hydroxyvitamin D(2) was well tolerated with main toxicities being hypercalcemia and renal insufficiency. All of the toxicity was reversible with drug discontinuation. Evidence for drug activity was seen in surrogate markers, and pharmacokinetic analysis showed substantial increases in vitamin D metabolite levels among the various cohorts. Whereas the defined maximum tolerated dose was not reached, the recommended Phase II dose was 12.5 microg/day given continuously.

Thyroid function in postmenopausal women with breast cancer on tamoxifen.

In 42 postmenopausal women with breast cancer, aged 48-85 years (mean age 62.4 years) serum thyroid hormone concentrations were measured before and after 6 months of tamoxifen therapy (20 mg daily). In particular triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroxine-binding globulin (TBG) and thyroid-stimulating hormone (TSH) concentrations before and 30 minutes after thyrotrophin-releasing hormone (TRH) administration (200 microg i.v.) were measured before and 6 months after tamoxifen therapy. T3 and T4 concentrations increased significantly (p<0.001 and p<0.05, respectively) whereas FT3 and FT4 remained unchanged (p>0.05), TBG increased significantly (p<0.001) and basal TSH concentrations as well as TSH response to TRH injection increased significantly (p<0.05) after tamoxifen therapy. It is concluded that tamoxifen administration changes thyroid hormone concentrations. However free thyroid hormone levels remain unchanged and the patients remain euthyroid after long-term tamoxifen therapy.