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Trabectedine

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https://www.readbyqxmd.com/read/28626402/effect-of-the-combination-of-trabectedin-and-pegylated-liposomal-doxorubicin-in-a-brca2-mutation-carrier-with-recurrent-platinum-sensitive-ovarian-cancer
#1
María Jesús Rubio Pérez
INTRODUCTION: The current standard of care for ovarian cancer is optimal cytoreduction with adjuvant chemotherapy based on a platinum/taxane combination. Although the response rate to this therapy is high, most patients ultimately relapse. Response to second-line therapy and prognosis are linked to the platinum-free interval (PFI); when both improve, the PFI increases. As a result, there is an increasing interest in the PFI extension strategies including platinum-free combinations. CASE PRESENTATION: A 50-year-old postmenopausal woman presented with ovarian serous carcinoma with peritoneal carcinomatosis...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28600866/bone-mass-is-compromised-by-the-chemotherapeutic-trabectedin-in-association-with-effects-on-osteoblasts-and-macrophage-efferocytosis
#2
Benjamin P Sinder, Laura Zweifler, Amy J Koh, Megan N Michalski, Lorenz C Hofbauer, Jose Ignacio Aguirre, Hernan Roca, Laurie K McCauley
Macrophages have established roles supporting bone formation. Despite their professional phagocytic nature, the role of macrophage phagocytosis in bone homeostasis is not well understood. Interestingly, apoptosis is a pivotal feature of cellular regulation and the primary fate of osteoblasts is apoptosis. Efferocytosis (phagocytosis of apoptotic cells) is a key physiologic process for the homeostasis of many tissues, and is associated with expression of osteoinductive factors. To test effects of macrophage depletion and compromised phagocytosis on bone, 16 wk old male C57BL/6J mice were treated with trabectedin - a chemotherapeutic with established anti-macrophage effects...
June 10, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28600479/trabectedin-overrides-osteosarcoma-differentiative-block-and-reprograms-the-tumor-immune-environment-enabling-effective-combination-with-immune-checkpoint-inhibitors
#3
Chiara Ratti, Laura Botti, Valeria Cancila, Silvia Galvan, Ilaria Torselli, Cecilia Garofalo, Maria Cristina Manara, Lucia Bongiovanni, Cesare F Valenti, Alessia Burocchi, Mariella Parenza, Barbara Cappetti, Sabina Sangaletti, Claudio Tripodo, Katia Scotlandi, Mario P Colombo, Claudia Chiodoni
Purpose: Osteosarcoma (OS), the most common primary bone tumor, is characterized by an aggressive behavior with high tendency to develop lung metastases as well as by multiple genetic aberrations that have hindered the development of targeted therapies. New therapeutic approaches are urgently needed; however, novel combinations with immunotherapies and checkpoint inhibitors require suitable preclinical models with intact immune systems to be properly tested. <p>Experimental Design: We have developed immuno-competent OS models that grow orthotopically in the bone and spontaneously metastasize to the lungs, mimicking human OS...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28574933/real-world-management-of-trabectedin-pegylated-liposomal-doxorubicin-in-platinum-sensitive-recurrent-ovarian-cancer-patients-a-national-survey
#4
Gabriella Ferrandina, Giulia Amadio, Ida Paris, Mariagrazia Distefano, Eleonora Palluzzi, Rosa de Vincenzo, Caterina Ricci, Giovanni Scambia
BACKGROUND: Trabectedin (T) plus pegylated liposomal doxorubicin (PLD) is approved for treatment of platinum-sensitive recurrent ovarian cancer (ROC). Despite the recommendations and guidelines, variations in managing T/PLD administration in routine clinical practice cannot be excluded. We aimed at setting up an Italian survey collecting data about management of T/PLD administration in ROC patients. METHODS: We carried out the development of a questionnaire-based survey on routine clinical practice in the management of ROC patients administered T/PLD...
June 1, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28547734/systemic-therapy-for-soft-tissue-sarcoma-proposals-for-the-optimal-use-of-pazopanib-trabectedin-and-eribulin
#5
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...
May 25, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28537897/mek-inhibitors-cobimetinib-and-trametinib-regressed-a-gemcitabine-resistant-pancreatic-cancer-patient-derived-orthotopic-xenograft-pdox
#6
Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Tasuku Kiyuna, Thinzar M Lwin, Ho Kyoung Hwang, Jonathan C Delong, Bryan M Clary, Michael Bouvet, Michiaki Unno, Robert M Hoffman
A pancreatic ductal adenocarcinoma (PDAC), obtained from a patient, was grown orthotopically in the pancreatic tail of nude mice to establish a patient-derived orthotopic (PDOX) model. Seven weeks after implantation, PDOX nude mice were divided into the following groups: untreated control (n = 7); gemcitabine (100 mg/kg, i.p., once a week for 2 weeks, n = 7); cobimetinib (5 mg/kg, p.o., 14 consecutive days, n = 7); trametinib (0.3 mg/kg, p.o., 14 consecutive days, n = 7); trabectedin (0.15 mg/kg, i.v., once a week for 2 weeks, n = 7); temozolomide (25 mg/kg, p...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28534249/trabectedin-and-eribulin-where-do-they-fit-in-the-management-of-soft-tissue-sarcoma
#7
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/28529743/omental-synovial-sarcoma-mimicking-an-ovarian-malignancy-a-case-report
#8
Naoyuki Iwahashi, Yoko Deguchi, Yuko Horiuchi, Kazuhiko Ino, Kenichi Furukawa
Synovial sarcoma is clinically rare, and cases of synovial sarcoma arising in the omentum are particularly rare. Only 3 cases have been reported in the literature to dtae, and they were associated with a poor prognosis. We herein report a rare case of aggressive primary omental synovial sarcoma presenting as an ovarian malignancy. A 53-year-old multigravida woman was referred to our hospital due to progressive abdominal distension. Magnetic resonance imaging revealed a large heterogeneous mass with an irregular component occupying the lower abdominal cavity, with an intact uterus...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28526720/efficacy-of-trabectedin-in-patients-with-advanced-translocation-related-sarcomas-pooled-analysis-of-two-phase-ii-studies
#9
Mitsuru Takahashi, Shunji Takahashi, Nobuhito Araki, Hideshi Sugiura, Takafumi Ueda, Tsukasa Yonemoto, Hideo Morioka, Hiroaki Hiraga, Toru Hiruma, Toshiyuki Kunisada, Akihiko Matsumine, Masashi Shimura, Akira Kawai
BACKGROUND: Trabectedin is reported as effective, especially against translocation-related sarcomas (TRSs) after failure of or intolerance to standard chemotherapy. We conducted two phase II studies of TRS, confirming high efficacy of 1.2 mg/m(2) trabectedin. The updated data of 66 patients in these studies was integrated to evaluate the efficacy of trabectedin against each histological subtype, and analyze final overall survival (OS). METHODS: Trabectedin was administered on day one of a 21-day cycle...
May 18, 2017: Oncologist
https://www.readbyqxmd.com/read/28512407/severe-rhabdomyolysis-during-treatment-with-trabectedin-in-combination-with-a-herbal-drug-in-a-patient-with-metastatic-synovial-sarcoma-a-case-report
#10
Angela Damato, Mario Larocca, Ermanno Rondini, Massimo Menga, Carmine Pinto, Annibale Versari
Rhabdomyolysis is defined as dissolution of striped muscle characterized by leakage of intracellular muscle components into the circulation, which can ultimately lead to renal failure with a possible fatal outcome. This is an uncommon side effect of trabectedin which is used in second-line therapy of metastatic sarcoma after anthracycline and ifosfamide failure. Here, we describe a case of reversible rhabdomyolysis in a male patient with recurrent metastatic synovial sarcoma of the hand, with marked (18)F-FDG uptake into his skeletal muscles, after 4 cycles of trabectedin, and who at the same time was taking an alternative medicine (bioflavonoids) suspected of triggering this adverse event...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28499583/histotype-tailored-neoadjuvant-chemotherapy-versus-standard-chemotherapy-in-patients-with-high-risk-soft-tissue-sarcomas-isg-sts-1001-an-international-open-label-randomised-controlled-phase-3-multicentre-trial
#11
Alessandro Gronchi, Stefano Ferrari, Vittorio Quagliuolo, Javier Martin Broto, Antonio Lopez Pousa, Giovanni Grignani, Umberto Basso, Jean-Yves Blay, Oscar Tendero, Robert Diaz Beveridge, Virginia Ferraresi, Iwona Lugowska, Domenico Franco Merlo, Valeria Fontana, Emanuela Marchesi, Davide Maria Donati, Elena Palassini, Emanuela Palmerini, Rita De Sanctis, Carlo Morosi, Silvia Stacchiotti, Silvia Bagué, Jean Michelle Coindre, Angelo Paolo Dei Tos, Piero Picci, Paolo Bruzzi, Paolo Giovanni Casali
BACKGROUND: Previous trials from our group suggested an overall survival benefit with five cycles of adjuvant full-dose epirubicin plus ifosfamide in localised high-risk soft-tissue sarcoma of the extremities or trunk wall, and no difference in overall survival benefit between three cycles versus five cycles of the same neoadjuvant regimen. We aimed to show the superiority of the neoadjuvant administration of histotype-tailored regimen to standard chemotherapy. METHODS: For this international, open-label, randomised, controlled, phase 3, multicentre trial, patients were enrolled from 32 hospitals in Italy, Spain, France, and Poland...
May 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28494349/trabectedin-and-campthotecin-synergistically-eliminate-cancer-stem-cells-in-cell-of-origin-sarcoma-models
#12
Lucia Martinez-Cruzado, Juan Tornin, Aida Rodriguez, Laura Santos, Eva Allonca, Maria Teresa Fernandez-Garcia, Aurora Astudillo, Juana Maria Garcia-Pedrero, Rene Rodriguez
Trabectedin has been approved for second-line treatment of soft tissue sarcomas. However, its efficacy to target sarcoma initiating cells has not been addressed yet. Here, we used pioneer models of myxoid/round cell liposarcoma (MRCLS) and undifferentiated pleomorphic sarcoma (UPS) developed from transformed human mesenchymal stromal/stem cells (MSCs) to evaluate the effect of trabectedin in the cell type responsible for initiating sarcomagenesis and their derived cancer stem cells (CSC) subpopulations. We found that low nanomolar concentrations of trabectedin efficiently inhibited the growth of sarcoma-initiating cells, induced cell cycle arrest, DNA damage and apoptosis...
May 8, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28494180/intra-arterial-administration-of-tumor-targeting-salmonella-typhimurium-a1-r-regresses-a-cisplatin-resistant-relapsed-osteosarcoma-in-a-patient-derived-orthotopic-xenograft-pdox-mouse-model
#13
Kentaro Igarashi, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Scott D Nelson, Sarah M Dry, Yunfeng Li, Jane Yanagawa, Tara A Russell, Arun S Singh, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Previously, a patient-derived orthotopic xenograft (PDOX) model was established with a lung metastasis from an osteosarcoma patient which developed after adjuvant cisplatinum (CDDP) treatment. In this model, we previously demonstrated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared with CDDP. In the present report, osteosarcoma tissue was implanted orthotopically in the distal femur of mice which were randomized into the following groups when tumor volume reached approximately 100 mm(3); On day 14 after initiation of treatment, all but CDDP significantly inhibited tumor volume growth compared with untreated controls...
May 11, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28467918/higher-antitumor-activity-of-trabectedin-in-germline-brca2-carriers-with-advanced-breast-cancer-as-compared-to-brca1-carriers-a-subset-analysis-of-a-dedicated-phase-ii-trial
#14
Amal Ghouadni, Suzette Delaloge, Pilar Lardelli, Carmen Kahatt, Tomasz Byrski, Joanne L Blum, Anthony Gonçalves, Mario Campone, Antonio Nieto, Vicente Alfaro, Martin Cullell-Young, Jan Lubinski
Specific alkylators may allow synthetic lethality among patients with germline BRCA1/2-mutations related cancers. The tetrahydroisoquinolone trabectedin administered at 1.3 mg/m(2) as a 3-h intravenous infusion every 3 weeks showed activity in patients with pretreated metastatic breast cancer (MBC) and BRCA germline mutations, but mainly in BRCA2 carriers. Data from a phase II study were retrospectively analyzed to compare the efficacy and safety of this trabectedin dose and schedule in pretreated MBC patients bearing germline BRCA1/2 mutations...
April 30, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28460536/review-of-past-and-present-clinical-cases-with-a-view-to-future-treatment-options
#15
Javier Martín-Broto, Peter Reichardt, Silvia Stacchiotti, Jean-Yves Blay
In the 10 years that have elapsed since trabectedin was first granted approval in Europe for treatment of advanced soft tissue sarcoma (STS), other cytotoxic agents and targeted therapies have been approved and numerous randomized controlled trials have been completed or are underway. As an academic exercise and positive proof of the advances in STS management that have occurred during the past decade, it is interesting to compare current and future treatment approaches. In this review, present and future treatment approaches are examined by case study for three STS subtypes: uterine leiomyosarcoma, abdominal dedifferentiated liposarcoma and malignant solitary fibrous tumor...
May 2, 2017: Future Oncology
https://www.readbyqxmd.com/read/28460535/intensity-of-recent-years-in-the-investigation-of-soft-tissue-sarcoma
#16
Jean-Yves Blay
The European Medicines Agency's approval in 2007 of trabectedin for treatment of advanced soft tissue sarcoma (STS) - the first new agent approved in this indication for more than 30 years - coincided with the start of an exciting era in sarcoma research. Over the past 10 years, several other cytotoxic agents and targeted therapies have been approved for use in advanced STS and research efforts continue to intensify. In parallel, the virtual explosion of new evidence has presented its own set of challenges in terms of interpreting the data and understanding how it may apply to individual patients...
May 2, 2017: Future Oncology
https://www.readbyqxmd.com/read/28454547/parp1-expression-drives-the-synergistic-antitumor-activity-of-trabectedin-and-parp1-inhibitors-in-sarcoma-preclinical-models
#17
Ymera Pignochino, Federica Capozzi, Lorenzo D'Ambrosio, Carmine Dell'Aglio, Marco Basiricò, Marta Canta, Annalisa Lorenzato, Francesca Vignolo Lutati, Sandra Aliberti, Erica Palesandro, Paola Boccone, Danilo Galizia, Sara Miano, Giulia Chiabotto, Lucia Napione, Loretta Gammaitoni, Dario Sangiolo, Maria Serena Benassi, Barbara Pasini, Giovanna Chiorino, Massimo Aglietta, Giovanni Grignani
BACKGROUND: Enhancing the antitumor activity of the DNA-damaging drugs is an attractive strategy to improve current treatment options. Trabectedin is an isoquinoline alkylating agent with a peculiar mechanism of action. It binds to minor groove of DNA inducing single- and double-strand-breaks. These kinds of damage lead to the activation of PARP1, a first-line enzyme in DNA-damage response pathways. We hypothesized that PARP1 targeting could perpetuate trabectedin-induced DNA damage in tumor cells leading finally to cell death...
April 28, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28404587/cic-dux4-induces-small-round-cell-sarcomas-distinct-from-ewing-sarcoma
#18
Toyoki Yoshimoto, Miwa Tanaka, Mizuki Homme, Yukari Yamazaki, Yutaka Takazawa, Cristina R Antonescu, Takuro Nakamura
CIC-DUX4 sarcoma (CDS) or CIC-rearranged sarcoma is a subcategory of small round cell sarcoma resembling the morphological phenotypes of Ewing sarcoma (ES). However, recent clinicopathologic and molecular genetic analyses indicate that CDS is an independent disease entity from ES. Few ancillary markers have been used in the differential diagnosis of CDS, and additional CDS-specific biomarkers are needed for more definitive classification. Here, we report the generation of an ex vivo mouse model for CDS by transducing embryonic mesenchymal cells (eMC) with human CIC-DUX4 cDNA...
April 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/28399901/activity-of-trabectedin-and-the-parp-inhibitor-rucaparib-in-soft-tissue-sarcomas
#19
Audrey Laroche, Vanessa Chaire, François Le Loarer, Marie-Paule Algéo, Christophe Rey, Kevin Tran, Carlo Lucchesi, Antoine Italiano
BACKGROUND: Trabectedin has recently been approved in the USA and in Europe for advanced soft-tissue sarcoma patients who have been treated with anthracycline-based chemotherapy without success. The mechanism of action of trabectedin depends on the status of both the nucleotide excision repair (NER) and homologous recombination (HR) DNA repair pathways. Trabectedin results in DNA double-strand breaks. We hypothesized that PARP-1 inhibition is able to perpetuate trabectedin-induced DNA damage...
April 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28284173/patient-derived-solitary-fibrous-tumour-xenografts-predict-high-sensitivity-to-doxorubicin-dacarbazine-combination-confirmed-in-the-clinic-and-highlight-the-potential-effectiveness-of-trabectedin-or-eribulin-against-this-tumour
#20
S Stacchiotti, M Saponara, R Frapolli, M Tortoreto, D Cominetti, S Provenzano, T Negri, G P Dagrada, A Gronchi, C Colombo, B Vincenzi, G Badalamenti, V Zuco, S L Renne, P Collini, C Morosi, A P Dei Tos, E Bello, S Pilotti, P G Casali, M D'Incalci, N Zaffaroni
BACKGROUND: Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. MATERIAL AND METHODS: Two dedifferentiated-SFT (D-SFT) models obtained from patients' biopsies were grown in immunodeficient mice...
May 2017: European Journal of Cancer
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