A phase II study of eribulin mesylate (E7389) in patients with advanced, previously treated non-small-cell lung cancer.

INTRODUCTION: This open-label phase II study assessed the efficacy and tolerability of eribulin, a non-taxane microtubule dynamics inhibitor with novel mechanism of action, as monotherapy in patients who have advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Enrolled patients had progressed during or after platinum-based doublet chemotherapy. Initially, two patient cohorts (taxane-pre-treated and taxane-naïve) received eribulin mesylate (1.4 mg/m(2)) as a 2- to 5-minute intravenous infusion on days 1, 8, and 15 of a 28-day cycle. To assess tolerability of a second dosing schedule, a cohort of taxane-pre-treated patients received eribulin on days 1 and 8 of a 21-day cycle. The primary endpoint was objective response rate (ORR) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) by independent radiographic review. RESULTS: One hundred three patients received eribulin. The ORR was 9.7% (all partial responses [PR]). Overall disease control rate (PR + stable disease) was 55.3%. Median duration of response, progression-free survival, and overall survival were 5.8, 3.4, and 9.4 months, respectively. The most common drug-related adverse events were neutropenia (54%; 49% grade 3/4); fatigue (49%; 11% grade 3, no grade 4); nausea (38%; 1% grade 3, no grade 4); alopecia (32%); anemia (29%, 4% grade 3/4) and neuropathy (23%; 2% grade 3, no grade 4). The 28-day schedule was associated with many dose delays, interruptions, or omissions due to neutropenia (day 15). The 21-day cycle was well-tolerated. CONCLUSIONS: Eribulin monotherapy administered on days 1 and 8 of a 21-day cycle is active and tolerated as second- or later-line chemotherapy for NSCLC.

Soy isoflavone intake and estrogen excretion patterns in young women: effect of probiotic administration.

BACKGROUND: Soy isoflavones may lower breast cancer risk through altered hepatic estrogen metabolism, leading to increased urinary excretion ratios of 2-hydroxyestrone (20HE1) to 16a-hydroxyestrone (16alphaOHE1). MATERIALS AND METHODS: Urinary excretion of 20HE1/16alphaOHE1 was measured in 36 healthy, pre-menstrual women before and after ingestion of a soy-protein formula containing 120 mg of isoflavone daily for one month. Since isoflavone absorption and metabolism depends on intestinal bacteria, effects of co-administration of Lactobacillus GG (2 x 10(12)) on estrogen ratios and isoflavone excretion were studied. Urinary isoflavone excretion measurements assessed compliance. RESULTS: Soy isoflavone ingestion induced quantitative differences in urinary excretion of estrogen metabolites and isoflavones but failed to alter 20HE1/16alphaOHE1 ratios. Co-administration of Lactobacillus GG with soy reduced excretion of total and individual isoflavones by 40% (p=0.08), without altering 2OHE1/16alphaOHE1 ratios. CONCLUSION: Isoflavone-rich soy protein administration alone, or with probiotic supplement, did not alter urinary excretion of estrogen metabolites in premenopausal women. However, adding concentrated probiotics may alter isoflavone bioavailability.