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Trabectedine

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https://www.readbyqxmd.com/read/29429842/trabectedin-in-ovarian-cancer-is-it-now-a-standard-of-care
#1
J Ventriglia, I Paciolla, S C Cecere, C Pisano, M Di Napoli, L Arenare, S V Setola, N S Losito, D Califano, M Orditura, S Pignata
In patients with recurrent ovarian cancer, the choice of second-line therapy is complex. Several factors have to be considered, such as platinum-free interval (PFI), residual toxicity from the previous treatments, BRCA1/2 gene mutation status. Trebectedin is a minor groove DNA binder derived from a marine organism that has shown efficacy in different settings in ovarian cancer therapy. It has been approved in the treatment of partially platinum sensitive (PPS) (PFI between 6 and 12 months) relapsed ovarian cancer according to the statistically significant progression-free survival (7...
February 8, 2018: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/29308326/depletion-of-tumor-associated-macrophages-switches-the-epigenetic-profile-of-pancreatic-cancer-infiltrating-t-cells-and-restores-their-anti-tumor-phenotype
#2
Simone Borgoni, Andrea Iannello, Santina Cutrupi, Paola Allavena, Maurizio D'Incalci, Francesco Novelli, Paola Cappello
Pancreatic Ductal Adenocarcinoma (PDA) is characterized by a complex tumor microenvironment that supports its progression, aggressiveness and resistance to therapies. The delicate interplay between cancer and immune cells creates the conditions for PDA development, particularly due to the functional suppression of T cell anti-tumor effector activity. However, some of the mechanisms involved in this process are still poorly understood. In this study, we analyze whether the functional and epigenetic profile of T cells that infiltrate PDA is modulated by the microenvironment, and in particular by tumor-associated macrophages (TAMs)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29286911/primary-breast-angiosarcoma-a-single-institution-experience-from-a-tertiary-cancer-center-in-south%C3%A2-india
#3
D Lokanatha, Abhishek Anand, K C Lakshmaiah, K Govind Babu, Linu Abraham Jacob, M C Suresh Babu, K N Lokesh, A H Rudresha, L K Rajeev, Smitha C Saldanha, G V Giri, Deepak Koppaka, Rekha V Kumar
INTRODUCTION: Primary angiosarcoma of the breast is a rare entity with incidence of less than 0.05% of all malignant breast neoplasms. It occurs in young females without any associated risk factors. The tumor behaves aggressively and has a poor prognosis compared to invasive ductal carcinoma. METHOD: It was a retrospective observational study done at a tertiary cancer center from January 2012 to December 2016. The medical records of patients diagnosed with primary breast angiosarcoma were reviewed for the study...
December 28, 2017: Breast Disease
https://www.readbyqxmd.com/read/29273061/diagnosis-and-treatment-of-alt-tumors-is-trabectedin-a-new-therapeutic-option
#4
REVIEW
Luca Pompili, Carlo Leonetti, Annamaria Biroccio, Erica Salvati
Telomeres are specialized nucleoprotein structures responsible for protecting chromosome ends in order to prevent the loss of genomic information. Telomere maintenance is required for achieving immortality by neoplastic cells. While most cancer cells rely on telomerase re-activation for linear chromosome maintenance and sustained proliferation, a significant population of cancers (10-15%) employs telomerase-independent strategies, collectively referred to as Alternative Lengthening of Telomeres (ALT). ALT mechanisms involve different types of homology-directed telomere recombination and synthesis...
December 22, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29250486/systemic-therapy-in-metastatic-or-unresectable-well-differentiated-dedifferentiated-liposarcoma
#5
REVIEW
Yevette McGovern, Charlie D Zhou, Robin L Jones
Liposarcoma is one of the most common subtypes of soft-tissue sarcoma and consists of three main subtypes, of which well-differentiated liposarcoma and dedifferentiated liposarcoma account for 40-45%. The current mainstay of systemic treatment for patients with metastatic or unresectable disease remains doxorubicin with or without ifosfamide in the first-line setting. Recently, eribulin and trabectedin have been approved by the US Food and Drug Administration for recurrent liposarcomas and progress in molecular characterization of these tumors has opened up new and potential novel treatment targets...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29232464/treatment-of-recurrent-ovarian-cancer
#6
S Pignata, S C Cecere, A Du Bois, P Harter, F Heitz
Despite optimal surgery and appropriate first-line chemotherapy, ∼70%-80% of patients with epithelial ovarian cancer will develop disease relapse. The same modalities as used primarily are available for treatment of recurrent ovarian cancer (ROC). The rationale for repetitive surgery in ROC was based on a stable body of retrospective data; however, prospective data were missing. Now, preliminary data from the prospective AGO-DESKTOP III give evidence that surgery for ROC seems to be of benefit for selected patients with platinum-sensitive relapse undergoing complete resection...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29220290/synovial-sarcoma-current-concepts-and-future-perspectives
#7
Silvia Stacchiotti, Brian Andrew Van Tine
Synovial sarcoma (SS) is a rare sarcoma driven by a translocation between SS18 and SSX 1, 2, or 4. With approximately 800 to 1,000 cases a year in the United States, it most commonly affects young adults between the ages of 15 and 30 years. The resultant tumors are either monophasic (pure sarcomas), biphasic (a combination or epithelioid and sarcomatous components), or poorly differentiated. The hybrid transcription factor SS18:SSX alters SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling and global methylation patterns that may allow for future therapeutic opportunities...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29194075/cutaneous-angiosarcoma-update-on-biology-and-latest-treatment
#8
Yoshihiro Ishida, Atsushi Otsuka, Kenji Kabashima
PURPOSE OF REVIEW: The present review aims to provide readers with the latest updates on the biology and clinical management of cutaneous angiosarcoma (cAS). RECENT FINDINGS: The genomic alteration of cAS is heterogeneous. Mutations are enriched in the mitosis-activated kinase (MAPK) pathway. Functional analysis has identified molecules that may serve as potential markers and therapeutic targets of angiosarcoma. These molecules include survivin, HSP90, FOXM1, miR-497-5p, KCa3...
November 30, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29177975/hepatic-safety-analysis-of-trabectedin-results-of-a-pharmacokinetic-study-with-trabectedin-in-patients-with-hepatic-impairment-and-experience-from-a-phase-3-clinical-trial
#9
Emiliano Calvo, Analia Azaro, Jordi Rodon, Luc Dirix, Manon Huizing, Francis Mark Senecal, Patricia LoRusso, Lorrin Yee, Italo Poggesi, Jan de Jong, Spyros Triantos, Youn C Park, Roland E Knoblauch, Trilok V Parekh, George D Demetri, Margaret von Mehren
Purpose Trabectedin is metabolized by the liver and has been associated with transient, noncumulative transaminase elevation. Two recent studies further characterize hepatic tolerability with trabectedin therapy: a phase 1 pharmacokinetic study (Study #1004; NCT01273493) in patients with advanced malignancies and hepatic impairment (HI), and a phase 3 study (Study #3007; NCT01343277) of trabectedin vs. dacarbazine in patients with advanced sarcomas and normal hepatic function. Methods In Study #1004, patients received a single 3-h intravenous (IV) infusion of trabectedin: control group, trabectedin 1...
November 27, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29020823/platinum-or-nonplatinum-in-recurrent-ovarian-cancer-that-is-the-question
#10
Andrés Poveda, Christian Marth
Although platinum-based chemotherapy continues to be the first-line option for advanced ovarian cancer and for platinum recurrences beyond 6 months, platinum rechallenge is not the best approach for some patients, such as those with residual toxicities, platinum-related hypersensitivity reactions or limited platinum-sensitivity (i.e., a platinum treatment-free interval [TFIp] of 6-12 months). Results of the MITO-8 study called into question the role of single-agent nonplatinum-based regimens in this specific subset of ovarian cancer patients...
October 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/29020822/trabectedin-mechanism-of-action-and-platinum-resistance-molecular-rationale
#11
Isabelle Ray-Coquard
Trabectedin presents a complex mode of action affecting key cell biology processes in tumor cells and in the tumor microenvironment. In ovarian cancer patients with a platinum treatment-free interval of 6-12 months treated with trabectedin + pegylated liposomal doxorubicin (PLD) or single-agent PLD, and retreated with platinum after relapse, overall survival was significantly prolonged in the trabectedin + PLD group. Mechanisms by which trabectedin restores tumor sensitivity to platinum include its interaction with components of the nucleotide excision repair machinery in tumor cells and inhibition of inflammatory mediators such as IL-6 in the tumor microenvironment...
October 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/29020821/when-nonplatinum-is-the-answer-the-role-of-trabectedin-plus-pegylated-liposomal-doxorubicin-in-recurrent-ovarian-cancer
#12
Nicoletta Colombo
Trabectedin + pegylated liposomal doxorubicin (PLD) offers a well tolerated and effective nonplatinum, nontaxane alternative for treatment of ovarian cancer patients with a treatment-free interval after platinum beyond 6 months, especially for those relapsing between 6 and 12 months and those who are not candidates to receive platinum-based therapy. Using the nonplatinum trabectedin + PLD combination gives patients time to recover from platinum-related toxicities and may restore platinum sensitivity in tumor cells...
October 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/28977930/a-patient-derived-orthotopic-xenograft-pdox-mouse-model-of-a-cisplatinum-resistant-osteosarcoma-lung-metastasis-that-was-sensitive-to-temozolomide-and-trabectedin-implications-for-precision-oncology
#13
Kentaro Igarashi, Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Miyake, Yong Zhang, Scott D Nelson, Sarah M Dry, Yunfeng Li, Jane Yanagawa, Tara A Russell, Arun S Singh, Hiroyuki Tsuchiya, Irmina Elliott, Fritz C Eilber, Robert M Hoffman
In the present study, we evaluated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared to cisplatinum (CDDP) on a patient-derived orthotopic xenogrraft (PDOX) of a lung-metastasis from an osteosarcoma of a patient who failed CDDP therapy. Osteosarcoma resected from the patient was implanted orthotopically in the distal femur of mice to establish PDOX models which were randomized into the following groups when tumor volume reached approximately 100 mm(3): G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal injection, weekly, for 2 weeks); G3, TRAB (0...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28976446/the-pharmacological-costs-of-second-line-treatments-for-recurrent-ovarian-cancer
#14
Jacopo Giuliani, Andrea Bonetti
INTRODUCTION: In ovarian cancer, it is uncertain which chemotherapy regimen is more clinically effective and cost-effective for the treatment of recurrence; therefore, it might be interesting to make a balance between the cost of the drugs administered and the difference in progression-free survival (PFS) and overall survival (OS). METHODS: The present evaluation was restricted to pivotal phase 3 randomized controlled trials. We calculated the pharmacological costs necessary to get the benefit in PFS and OS...
November 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28946142/short-infusion-trabectedin-in-heavily-pretreated-ovarian-cancer-patients-a-single-institution-experience
#15
Claudia Marchetti, Angela Musella, Alessia Romito, Laura Vertechy, Innocenza Palaia, Violante Di Donato, Serena Boccia, Francesca De Felice, Marco Monti, Ludovico Muzii, Pierluigi Benedetti Panici
OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of trabectedin given every 10 days as a single agent in recurrent ovarian cancer after 3 prior regimens. METHOD: Trabectedin 0.6 mg/m2 was administered as a 3-h infusion every 10 days on a 21-day cycle. The study population was compared to patients treated with weekly paclitaxel 80 mg/m2 intravenously on days 1, 8, 15, and 22 every 4 weeks. RESULTS: We identified 34 patients previously submitted to at least 3 lines of chemotherapy who received single-agent trabectedin between 2010 and 2015...
September 26, 2017: Oncology
https://www.readbyqxmd.com/read/28926423/a-noninterventional-multicenter-prospective-phase-iv-study-of-trabectedin-in-patients-with-advanced-soft-tissue-sarcoma
#16
Angela Buonadonna, Charlotte Benson, Jose Casanova, Bernd Kasper, Antonio López Pousa, Filomena Mazzeo, Thomas Brodowicz, Nicolas Penel
This prospective, noninterventional study is the first phase IV trial designed to evaluate trabectedin in patients with advanced soft tissue sarcoma in real-life clinical practice across Europe. To be included in the study, patients must have received more than or equal to one cycle of trabectedin and be currently on treatment. The primary endpoint was progression-free survival as defined by investigators. The secondary endpoints included objective response rate, disease control rate, time to progression and the growth modulation index (GMI), overall survival, and an assessment of the cancer-related symptoms and safety...
November 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28919822/uterine-sarcoma-current-perspectives
#17
REVIEW
Charlotte Benson, Aisha B Miah
Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade), undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types...
2017: International Journal of Women's Health
https://www.readbyqxmd.com/read/28835514/salvage-therapy-in-advanced-adult-soft-tissue-sarcoma-a-systematic-review-and-meta-analysis-of-randomized-trials
#18
REVIEW
Alessandro Comandone, Fausto Petrelli, Antonella Boglione, Sandro Barni
BACKGROUND: Prognosis for patients with metastatic soft tissue sarcomas (STS) is dismal, with median overall survival (OS) of 8-12 months. The role of second-line therapy has been inconsistently investigated over the last 20 years. This systematic review and meta-analysis was performed to assess the efficacy of salvage treatment in pretreated adult type STS, gastrointestinal stromal tumor (GIST) excluded. MATERIAL AND METHODS: PubMed, Web of Science, SCOPUS, EMBASE, CINAHL, and The Cochrane Library were searched for randomized phase II/phase III trials exploring second- or beyond therapy lines in pretreated metastatic STS...
December 2017: Oncologist
https://www.readbyqxmd.com/read/28782526/ascites-interferes-with-the-activity-of-lurbinectedin-and-trabectedin-potential-role-of-their-binding-to-alpha-1-acid-glycoprotein
#19
E Erba, M Romano, M Gobbi, M Zucchetti, M Ferrari, C Matteo, N Panini, B Colmegna, G Caratti, L Porcu, R Fruscio, M V Perlangeli, D Mezzanzanica, D Lorusso, F Raspagliesi, M D'Incalci
Trabectedin and its analogue lurbinectedin are effective drugs used in the treatment of ovarian cancer. Since the presence of ascites is a frequent event in advanced ovarian cancer we asked the question whether ascites could modify the activity of these compounds against ovarian cancer cells. The cytotoxicity induced by trabectedin or lurbinectedin against A2780, OVCAR-5 cell lines or primary culture of human ovarian cancer cells was compared by performing treatment in regular medium or in ascites taken from either nude mice or ovarian cancer patients...
November 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28774898/fda-approval-summary-trabectedin-for-unresectable-or-metastatic-liposarcoma-or-leiomyosarcoma-following-an-anthracycline-containing-regimen
#20
Amy Barone, Dow-Chung Chi, Marc R Theoret, Huanyu Chen, Kun He, Dubravka Kufrin, Whitney S Helms, Sriram Subramaniam, Hong Zhao, Anuja Patel, Kirsten B Goldberg, Patricia Keegan, Richard Pazdur
On October 23, 2015, the FDA approved trabectedin, a new molecular entity for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen. Approval was based on results of a single, randomized, active-controlled, 518-patient, multicenter study comparing the safety and efficacy of trabectedin 1.5 mg/m2 as a 24-hour continuous intravenous (i.v.) infusion once every 3 weeks with dacarbazine 1,000 mg/m2 i.v. once every 3 weeks. Treatment with trabectedin resulted in a statistically significant improvement in progression-free survival (PFS), with a PFS of 4...
December 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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