eribulin mesylate (also called E7389)

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eribulin mesylate (also called E7389):
http://www.cancer.gov/Templates/drug...x?CdrID=257773
Phase II trial results from 2008:
http://www.medicalnewstoday.com/articles/107642.php
and currently active trials:
http://www.cancer.gov/search/Results...archid=6018838

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1: J Clin Oncol. 2009 Apr 6. [Epub ahead of print] Links

Phase II Study of Eribulin Mesylate, a Halichondrin B Analog, in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane.

Vahdat LT, Pruitt B, Fabian CJ, Rivera RR, Smith DA, Tan-Chiu E, Wright J, Tan AR, Dacosta NA, Chuang E, Smith J, O'Shaughnessy J, Shuster DE, Meneses NL, Chandrawansa K, Fang F, Cole PE, Ashworth S, Blum JL.
Weill Cornell Medical College, New York; State University of New York Upstate Medical University, Syracuse; and Stony Brook University Hospital, Stony Brook, NY; Harrington Cancer Center, Amarillo; El Paso Cancer Center, Texas Oncology PA and US Oncology, EI Paso; Baylor Charles A. Sammons Cancer Center, Texas Oncology PA and US Oncology, Dallas, TX; University of Kansas Medical Center, Kansas City, KS; Northwest Cancer Specialists, Vancouver, WA; Florida Cancer Research Institute, Davie, FL; Cancer Institute of New Jersey, New Brunswick; and Eisai Medical Research Inc, Ridgefield Park, NJ.
PURPOSE: Eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor, is a structurally simplified, synthetic analog of the marine natural product halichondrin B. This open-label, single-arm, phase II study evaluated efficacy and tolerability of eribulin in heavily pretreated patients with metastatic breast cancer (MBC). METHODS: MBC patients who were previously treated with an anthracycline and a taxane received eribulin mesylate (1.4 mg/m(2)) as a 2- to 5-minute intravenous (IV) infusion on days 1, 8, and 15 of a 28-day cycle. Because of neutropenia (at day 15), an alternative regimen of eribulin on days 1 and 8 of a 21-day cycle was administered. The primary end point was overall response rate. RESULTS: Of the 103 patients treated, the median number of prior chemotherapy regimens was four (range, one to 11 regimens). In the per-protocol population (n = 87), eribulin achieved an independently reviewed objective response rate (all partial responses [PRs]) of 11.5% (95% CI, 5.7 to 20.1) and a clinical benefit rate (PR plus stable disease >/= 6 months) of 17.2% (95% CI, 10.0 to 26.8). The median duration of response was 171 days (5.6 months; range, 44 to 363 days), the median progression-free survival was 79 days (2.6 months; range, 1 to 453 days), and the median overall survival was 275 days (9.0 months; range, 15 to 826 days). The most common drug-related grades 3 to 4 toxicities were as follows: neutropenia, 64%; leukopenia, 18%; fatigue, 5%; peripheral neuropathy, 5%; and febrile neutropenia, 4%. CONCLUSION: Eribulin demonstrated activity with manageable tolerability (including infrequent grade 3 and no grade 4 neuropathy) in heavily pretreated patients with MBC when dosed as a short IV infusion on days 1 and 8 of a 21-day cycle.

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Public release date: 9-Dec-2005
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Contact: Judee Shuler
judee_shuler@eisai.com
201-287-2241
JFK Communcations
Eisai announces Phase II data on E7389, a potential new therapy for the treatment of breast cancer

Marine sponge molecule is model for novel anti-tubulin agent

Researchers today presented preliminary safety and efficacy data for E7389 in the treatment of advanced, refractory breast cancer during the San Antonio Breast Cancer Symposium. E7389 is a synthetic analog of halichondrin B (HB), which is a natural product shown in preclinical studies to have highly potent anti-cancer activity in vitro and in vivo. Halichondrin B was originally isolated from a type of marine sponge. This study was designed to evaluate E7389 as a monotherapy in patients with refractory breast cancer. The primary endpoint of this trial was response rate, measured using the RECIST (Response Evaluation Criteria In Solid Tumors) criteria � a group of standards used to measure responses to treatment in solid tumors.
Of the 65 evaluable patients, 10 partial responses were confirmed at the 4th cycle assessment. Twenty-one patients had stable disease (SD). In treatment-refractory patients with advanced breast cancer this preliminary response rate (15%) appears promising.
Based on the preliminary results of this study, the predominant serious side effect related to E7389 was neutropenia (low white blood cell counts). Other side effects were considered mild to moderate and included nausea, fatigue, dehydration, arthralgias, dyspnea and neuropathy. None of the patients discontinued the study due to hematological toxicity.
"The results from this study with E7389 appear promising, and clinical research on E7389 as a treatment for breast cancer is continuing," said Sandra Silberman, MD, PhD, Associate Vice President and Global Therapeutic Area Head, Oncology at Eisai Medical Research Inc. "E7389 is an example of Eisai's human health care (hhc) commitment to satisfy unmet medical needs of patients and their families. Eisai has targeted oncology/critical care as one of three key therapeutic areas of focus," she added.
Seventy-one women were enrolled in the 28-day cycle patient group. Preliminary efficacy data for 65 patients and safety data on 48 patients are available. The 65 patients considered evaluable for response had completed at least their 2nd cycle of treatment and had a tumor assessment, which could be compared to their baseline. This study is ongoing, and final results may change from the initial analysis.
"My colleagues and I are very excited by the results of this study so far, " said Linda T. Vahdat, MD, Associate Professor of Clinical Medicine and Medical Director, Breast Cancer Program at Cornell University New York Presbyterian Hospital. "We look forward to additional studies with this novel compound."
Pre-clinical studies demonstrate that E7389 suppresses the growth of cellular microtubules, which are essential for cell division. By doing so, E7389 appears to stop the production of new cancer cells and ultimately results in the programmed death of the existing cancer cells, a process known as apoptosis.

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Eisai Plans to Submit Marketing Authorization Applications for Eribulin Mesylate in Locally Advanced or Metastatic Breast Cancer WOODCLIFF LAKE, N.J., Oct. 30
WOODCLIFF LAKE, N.J., Oct. 30 /PRNewswire/ -- Eisai Inc. today announced preliminary results from a recently completed Phase III study with eribulin mesylate (E7389), discovered and developed by the company, in patients with locally advanced or metastatic breast cancer.

This global Phase III study, known as "EMBRACE," (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389), was an open-label, randomized, parallel two-arm, multi-center study of 762 women with locally recurrent or metastatic breast cancer previously treated with at least two and a maximum of five prior chemotherapy regimens, including an anthracycline and a taxane.

The patients were treated either with eribulin (administered intravenously over two to five minutes on days 1 and 8 every 21 days) or with treatment of physician's choice. Treatment of physician's choice is defined as any single agent chemotherapy, hormonal treatment or biological therapy approved for the treatment of cancer; or palliative treatment or radiotherapy administered according to local practice.

Preliminary results from the study demonstrated a statistically significant improvement in overall survival, the primary endpoint, in eribulin-treated patients compared with the physician's choice of therapy. The safety profile of eribulin in this Phase III study was consistent with the adverse events seen in previous Phase II clinical studies and the most common adverse event reported was myelosuppression.

Eribulin is a new chemical compound discovered and developed by Eisai. It is a synthetic analogue of halichondrin B, a naturally-derived compound that was first isolated from a marine sponge. While taxanes inhibit cell division by stabilizing microtubules, eribulin is a microtubule dynamics inhibitor that arrests the cell cycle through inhibition of the growth of microtubules without interfering with microtubule shortening.