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https://www.readbyqxmd.com/read/28810913/selinexor-kpt-330-demonstrates-anti-tumor-efficacy-in-preclinical-models-of-triple-negative-breast-cancer
#1
Natalia Paez Arango, Erkan Yuca, Ming Zhao, Kurt W Evans, Stephen Scott, Charissa Kim, Ana Maria Gonzalez-Angulo, Filip Janku, Naoto T Ueno, Debu Tripathy, Argun Akcakanat, Aung Naing, Funda Meric-Bernstam
BACKGROUND: Selinexor (KPT-330) is an oral agent that has been shown to inhibit the nuclear exporter XPO1. Given the pressing need for novel therapies for triple-negative breast cancer (TNBC), we sought to determine the antitumor effects of selinexor in vitro and in vivo. METHODS: Twenty-six breast cancer cell lines of different breast cancer subtypes were treated with selinexor in vitro. Cell proliferation assays were used to measure the half-maximal inhibitory concentration (IC50) and to test the effects in combination with chemotherapy...
August 15, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28761747/eribulin-for-metastatic-breast-cancer-mbc-treatment-a-retrospective-multicenter-study-based-in-campania-south-italy-eri-001-trial
#2
Michele Orditura, Adriano Gravina, Ferdinando Riccardi, Anna Diana, Carmela Mocerino, Luigi Leopaldi, Alessio Fabozzi, Guido Giordano, Raffaele Nettuno, Pasquale Incoronato, Maria Luisa Barzelloni, Roberta Caputo, Agata Pisano, Giuseppe Grimaldi, Geppino Genua, Vincenzo Montesarchio, Enrico Barbato, Giovanni Iodice, Eva Lieto, Eugenio Procaccini, Roberto Mabilia, Antonio Febbraro, Michelino De Laurentiis, Fortunato Ciardiello
BACKGROUND: On the basis of the results of two pivotal phase III clinical trials, eribulin mesylate is currently approved in EU for the treatment of advanced breast cancer (aBC) in patients who have previously received an anthracycline and a taxane in either the adjuvant or the metastatic setting, and at least one chemotherapeutic regimen for metastatic disease. METHODS: In our study, we investigated the efficacy and tolerability of eribulin as second or further line chemotherapy in 137 women affected by aBC...
2017: ESMO Open
https://www.readbyqxmd.com/read/28741868/retrospective-analysis-of-the-efficacy-and-safety-of-eribulin-therapy-for-metastatic-breast-cancer-in-daily-practice
#3
Toshihiro Tanaka, Miho Ueno, Yuta Nakashima, Shotaro Chinen, Eiichi Sato, Michio Masaki, Ai Mogi, Hidenori Sasaki, Kazuo Tamura, Yasushi Takamatsu
BACKGROUND: Evidence of eribulin therapy for metastatic breast cancer (MBC) in clinical practice is not well documented. METHODS: We retrospectively analyzed the safety and efficacy of eribulin in 29 MBC patients from 2011 to 2016 at Fukuoka University Hospital. RESULTS: The median patient age, number of courses, total dose, and relative dose intensity were as follows: 65 years, five courses, 8.6 mg/m(2) , and 75%, respectively. One patient achieved a complete response, (CR) six a partial response (PR), eight stable disease (SD) and 14 patients exhibited progressive disease...
July 25, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28739698/highly-eribulin-resistant-kbv20c-oral-cancer-cells-can-be-sensitized-by-co-treatment-with-the-third-generation-p-glycoprotein-inhibitor-elacridar-at-a-low-dose
#4
Yujin Park, Ji-Yeon Son, Byung-Mu Lee, Hyung Sik Kim, Sungpil Yoon
BACKGROUND/AIM: Eribulin mesylate, also called Halaven® (HAL), was recently developed as a microtubule-targeting drug and is used in the clinic for resistant or metastatic cancer. Previously, we showed that P-glycoprotein (P-gp)-overexpressing KBV20C oral cancer cells are highly resistant to HAL compared to sensitive KB cells. This qualitative study was designed to identify specific P-gp inhibitors that increase the sensitivity of highly resistant cancer cells to HAL. MATERIALS AND METHODS: In order to identify functional P-gp inhibitors, HAL-treated KBV20C cells were co-treated with P-gp inhibitors, verapamil, elacridar, cyclosporine A, mitotane, piperine, fumagillin, curcumin, indomethacin, probenecid, sulindac, tesmilifene, and C-4...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28698435/-histology-specific-chemotherapy-in-soft-tissue-sarcomas
#5
Eisuke Kobayashi, Akira Kawai
Soft-tissue sarcomas(STSs)are rare mesenchymal tumors, accounting for less than 1%of all adult malignancies. STSs also have diversity, with more than 50 different histological subtypes. While surgical complete resection is a definitive treatment for localized STS, chemotherapy is the treatment option for managing locally advanced and metastatic STS. Although doxorubicin ±ifosfamide is still the first-line therapy for most STS subtypes, some STSs(alveolar soft part sarcoma, clear cell sarcoma, epithelioid sarcoma and extraskeletal myxoid chondrosarcoma)have been reported to have little response to these cytotoxic chemotherapies...
June 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28698434/-the-role-of-novel-agents-in-the-treatment-of-soft-tissue-sarcoma
#6
Yoichi Naito
Soft tissue sarcomas are rare disease and the development of efficacious drug is urgently needed. The challenge is continuing, and recently 2 drugs, trabectedin and eribulin, were approved in Japan. Both drugs were investigated in patients with liposarcoma or leiomyosarcoma in randomized phase III trials as compared to dacarbazine. Eribulin was superior in terms of overall survival and trabectedin was superior in terms of progression-free survival compared to dacarbazine. This article reviews the efficacy and safety of both drugs...
June 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28681998/eribulin-regresses-a-doxorubicin-resistant-ewing-s-sarcoma-with-a-fus-erg-fusion-and-cdkn2a-deletion-for-the-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model
#7
Kentaro Miyaki, Takashi Murakami, Tasuku Kiyuna, Kentaro Igarashi, Kei Kawaguchi, Yunfeng Li, Arun S Singh, Sarah M Dry, Mark A Eckardt, Yukihiko Hiroshima, Masashi Momiyama, Ryusei Matsuyama, Takashi Chishima, Itaru Endo, Fritz C Eilber, Robert M Hoffman
Ewing's sarcoma is a recalcitrant tumor greatly in need of more effective therapy. The aim of this study was to determine the efficacy of eribulin on a doxorubicin (DOX)-resistant Ewing's sarcoma patient derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma PDOX model was previously established in the right chest wall of nude mice from the patient's right chest wall. In the previous study, the Ewing's sarcoma PDOX was resistant to DOX and sensitive to palbociclib and linsitinib. In the present study, the PDOX models were randomized into 3 groups when the tumor volume reached 60 mm(3) : G1, untreated control (n = 6); G2, DOX treated (n = 6), intraperitoneal (i...
July 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28679691/metastatic-triple-negative-breast-cancer-patient-with-tp53-tumor-mutation-experienced-11-months-progression-free-survival-on-bortezomib-monotherapy-without-adverse-events-after-ending-standard-treatments-with-grade-3-adverse-events
#8
Tobias Meißner, Adam Mark, Casey Williams, Wolfgang E Berdel, Stephanie Wiebe, Andrea Kerkhoff, Eva Wardelmann, Timo Gaiser, Carsten Müller-Tidow, Philip Rosenstiel, Norbert Arnold, Brian Leyland-Jones, Andre Franke, Martin Stanulla, Michael Forster
A triple-negative breast cancer patient had no hereditary BRCA1, BRCA2, or TP53 risk variants. After exhaustion of standard treatments, she underwent experimental treatments and whole-exome sequencing of tumor, blood, and a metastasis. Well-tolerated experimental bortezomib monotherapy was administered for a progression-free period of 11 mo. After progression, treatments were changed and the exome data were evaluated, expanded with RNA and exome sequencing of a late-stage metastasis. In the final stage, eribulin alone and in combination with anthracyclines were administered...
July 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28664226/eribulin-shows-high-concentration-and-long-retention-in-xenograft-tumor-tissues
#9
Michiko Sugawara, Krista Condon, Earvin Liang, Christopher DesJardins, Edgar Schuck, Kazutomi Kusano, W George Lai
PURPOSE: Eribulin, a synthetic analog of the natural product halichondrin B, is a microtubule dynamics inhibitor. In this study, we report the pharmacokinetic profiles of eribulin in mice, rats, and dogs following intravenous administrations with optimized and validated bio-analytical methods. METHODS: Eribulin was administered at 0.5 and 2 mg/kg in mice, 0.5 and 1 mg/kg in rats, and 0.08 mg/kg in dogs. Tumor and brain penetration of eribulin was also evaluated in LOX human melanoma xenograft models...
August 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28662406/first-report-of-eribulin-in-combination-with-pertuzumab-and-trastuzumab-for-advanced-her2-positive-breast-cancer
#10
Kazuhiro Araki, Ippei Fukada, Hiroyo Yanagi, Kokoro Kobayashi, Tomoko Shibayama, Rie Horii, Shunji Takahashi, Futoshi Akiyama, Shinji Ohno, Yoshinori Ito
BACKGROUND: The efficacy and safety of continuing multiple anti-HER2 therapies in advanced breast cancer (ABC) patients remains unclear. This study investigated eribulin in combination with pertuzumab and trastuzumab for both taxane- and trastuzumab-pretreated HER2-positive ABC patients. METHODS: In a single-institute, single-arm, open-label, phase II trial, HER2-positive ABC patients who had previously received taxanes and trastuzumab were treated with eribulin in combination with pertuzumab and trastuzumab...
June 26, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28660549/safety-and-effectiveness-of-eribulin-in-japanese-patients-with-locally-advanced-or-metastatic-breast-cancer-a-post-marketing-observational-study
#11
Junichiro Watanabe, Yoshinori Ito, Shozo Ohsumi, Mitsuhiro Mizutani, Hideya Tashiro, Kenichi Sakurai, Masato Takahashi, Tsuyoshi Saito, Junji Tsurutani, Hirofumi Mukai, Tetsuhiro Yoshinami, Shintaro Takao, Yasuhisa Yamamoto, Toshiyuki Matsuoka, Hirotaka Iwase, Hiroji Iwata, Seigo Nakamura, Toshiaki Saeki
Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m(2)) on days 1 and 8 of every 3-week cycle. The primary endpoint was the frequency and intensity of adverse drug reactions (ADRs)...
June 29, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28621163/eribulin-in-advanced-liposarcoma-and-leiomyosarcoma
#12
REVIEW
Elisabetta Setola, Jonathan Noujaim, Charlotte Benson, Sant Chawla, Emanuela Palmerini, Robin L Jones
The heterogeneity of soft tissue sarcomas (STS) presents a formidable management challenge. Consequently, one of the main research goals is to define specific tailored therapy for each histological subtype and to develop a more personalised approach to treatment. The standard first line chemotherapy for advanced STS is doxorubicin, with or without ifosfamide, however, a number of different drugs are emerging as active therapies beyond first-line. Areas covered: Eribulin has recently been approved for advanced liposarcoma, after an anthracycline-containing regimen, demonstrating an overall survival (OS) advantage in liposarcoma and leiomyosarcoma in a randomised Phase III clinical trial...
August 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28612225/prolonged-survival-in-patients-with-breast-cancer-and-a-history-of-brain-metastases-results-of-a-preplanned-subgroup-analysis-from-the-randomized-phase-iii-beacon-trial
#13
Javier Cortés, Hope S Rugo, Ahmad Awada, Chris Twelves, Edith A Perez, Seock-Ah Im, Patricia Gómez-Pardo, Lee S Schwartzberg, Veronique Diéras, Denise A Yardley, David A Potter, Audrey Mailliez, Alvaro Moreno-Aspitia, Jin-Seok Ahn, Carol Zhao, Ute Hoch, Mary Tagliaferri, Alison L Hannah, Joyce O'Shaughnessy
PURPOSE: Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. METHODS: The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013...
June 13, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28578601/olaparib-for-metastatic-breast-cancer-in-patients-with-a-germline-brca-mutation
#14
Mark Robson, Seock-Ah Im, Elżbieta Senkus, Binghe Xu, Susan M Domchek, Norikazu Masuda, Suzette Delaloge, Wei Li, Nadine Tung, Anne Armstrong, Wenting Wu, Carsten Goessl, Sarah Runswick, Pierfranco Conte
BACKGROUND: Olaparib is an oral poly(adenosine diphosphate-ribose) polymerase inhibitor that has promising antitumor activity in patients with metastatic breast cancer and a germline BRCA mutation. METHODS: We conducted a randomized, open-label, phase 3 trial in which olaparib monotherapy was compared with standard therapy in patients with a germline BRCA mutation and human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer who had received no more than two previous chemotherapy regimens for metastatic disease...
August 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28547734/systemic-therapy-for-soft-tissue-sarcoma-proposals-for-the-optimal-use-of-pazopanib-trabectedin-and-eribulin
#15
REVIEW
Akira Kawai, Kan Yonemori, Shunji Takahashi, Nobuhito Araki, Takafumi Ueda
Soft tissue sarcoma (STS) is a rare tumor with more than 50 histologic subtypes. Although treatment outcomes for patients with STS have improved greatly over the past few decades owing to the adoption of a multidisciplinary approach, patients with advanced disease have a poor prognosis. The development of anticancer drugs has been directed toward improving overall survival (OS). Doxorubicin monotherapy is currently the only standard option for the first-line treatment of STS. However, there is no standard therapy for second-line and later treatment at present...
July 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28534249/trabectedin-and-eribulin-where-do-they-fit-in-the-management-of-soft-tissue-sarcoma
#16
REVIEW
Ravin Ratan, Shreyaskumar R Patel
Trabectedin and eribulin are two agents that have been recently approved for the treatment of specific soft tissue sarcoma subtypes. They have proved to be a much-needed line of additional treatment for patients with these rare tumors, but their activity remains admittedly modest in most cases. Further exploitation of these novel agents is likely to require a more granular understanding of the salient mechanisms of action. For example, if as some studies suggest, eribulin derives its benefit from restructuring of tumor vasculature to improve efficacy of subsequent lines of therapy, then patients may benefit from its use earlier in the treatment pathway...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28512389/evaluation-of-quality-of-life-at-progression-in-patients-with-soft-tissue-sarcoma
#17
Stacie Hudgens, Anna Forsythe, Ilias Kontoudis, David D'Adamo, Ashley Bird, Hans Gelderblom
Introduction. Soft Tissue Sarcoma (STS) is a rare malignancy of mesodermal tissue, with international incidence estimates between 1.8 and 5 per 100,000 per year. Understanding quality of life (QoL) and the detrimental impact of disease progression is critical for long-term care and survival. Objectives. The primary objective was to explore the relationship between disease progression and health-related quality of life (HRQoL) using data from Eisai's study (E7389-G000-309). Methods. This was a 1 : 1 randomized, open-label, multicenter, Phase 3 study comparing the efficacy and safety of eribulin versus dacarbazine in patients with advanced STS...
2017: Sarcoma
https://www.readbyqxmd.com/read/28492292/olaratumab-for-the-treatment-of-soft-tissue-sarcoma
#18
REVIEW
H A Deshpande, M Cecchini, S Ni Choileain, R Jones
Soft tissue sarcoma represents about 1% of all solid malignancies. The standard chemotherapy regimens have included doxorubicin alone or in combination with other agents. Despite recent advances in treatment beyond first line - with the FDA approval of pazopanib, eribulin and trabectidin - overall survival for patients with metastatic disease remains in the region of 12-19 months. Olaratumab is a monoclonal antibody directed against platelet-derived growth factor receptor alpha (PDGFRalpha). It was studied in a phase Ib and randomized phase II study in combination with doxorubicin in patients with soft tissue sarcoma who previously had not received doxorubicin for metastatic disease...
April 2017: Drugs of Today
https://www.readbyqxmd.com/read/28481188/eribulin-long-term-response-and-rechallenge-report-of-two-clinical-cases
#19
Elena Barbieri, Daniela Rubino, Rossella Hakim, Angela Fini, Manuela Lenzi, Claudio Zamagni
The antimitotic agent eribulin, a synthetic analog of halichondrin B isolated from a marine sponge, resulted particularly effective in improving the overall survival of heavily pretreated metastatic breast cancer (MBC) patients in randomized Phase III clinical trials and real-life studies. However, only scant information is available on the clinical experiences of patients who underwent long-lasting eribulin treatment followed by a rechallenge. Here we presented two cases of MBC women previously treated with several lines of chemotherapy and hormonal therapies, who underwent long-lasting treatment and rechallenge with eribulin, showing a partial response in both periods...
April 2017: Future Oncology
https://www.readbyqxmd.com/read/28481187/eribulin-rapidly-reduces-the-aggressiveness-of-second-primary-breast-cancer-a-case-report
#20
Isacco Falco, Silvia Stragliotto
The cytotoxic agent, eribulin represents a new standard of care in the treatment of heavily pretreated metastatic breast cancer patients. Here, we describe our experience with eribulin in a patient with a controlled primary breast cancer, who showed an aggressive recurrence of the primary tumor, including metastatic disease. Treatment management of the second primary tumor included six lines of chemotherapy and three lines of hormonal therapy, including eribulin as sixth line among all chemotherapies received...
April 2017: Future Oncology
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