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Trabectedin

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https://www.readbyqxmd.com/read/28723652/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
#1
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 mm3: G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal injection, weekly, for 2 weeks); G3, TRAB (0...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698435/-histology-specific-chemotherapy-in-soft-tissue-sarcomas
#2
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
#3
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/28698433/-molecular-target-therapy-for-soft-tissue-sarcoma
#4
Shunji Takahashi
Soft tissue sarcoma(STS)is one of the rare and intractable cancers, and most types of STS are not sensitive to chemotherapy. Development of specific molecular target therapy for each type of STS is necessary. There are specific chromosome translocations in 20-30% of STS, but their products are mostly transcriptional factors, and target therapy for those factors are difficult to develop. Trabectedin is an alkylating agent and is also inhibit function of transcriptional factors, and shows efficacy for translocation-related sarcoma(TRS)such as myxoid liposarcoma...
June 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28683469/lurbinectedin-reduces-tumour-associated-macrophages-and-the-inflammatory-tumour-microenvironment-in-preclinical-models
#5
Cristina Belgiovine, Ezia Bello, Manuela Liguori, Ilaria Craparotta, Laura Mannarino, Lara Paracchini, Luca Beltrame, Sergio Marchini, Carlos M Galmarini, Alberto Mantovani, Roberta Frapolli, Paola Allavena, Maurizio D'Incalci
BACKGROUND: Lurbinectedin is a novel anticancer agent currently undergoing late-stage (Phase II /III) clinical evaluation in platinum-resistant ovarian, BRCA1/2-mutated breast and small-cell lung cancer. Lurbinectedin is structurally related to trabectedin and it inhibits active transcription and the DNA repair machinery in tumour cells. METHODS: In this study we investigated whether lurbinectedin has the ability to modulate the inflammatory microenvironment and the viability of myeloid cells in tumour-bearing mice...
July 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28672777/correction-the-parp-inhibitor-olaparib-enhances-the-sensitivity-of-ewing-sarcoma-to-trabectedin
#6
José Luis Ordóñez, Ana Teresa Amaral, Angel M Carcaboso, David Herrero-Martín, María Del Carmen García-Macías, Vicky Sevillano, Diego Alonso, Guillem Pascual-Pasto, Laura San-Segundo, Monica Vila-Ubach, Telmo Rodrigues, Susana Fraile, Cristina Teodosio, Agustín Mayo-Iscar, Miguel Aracil, Carlos María Galmarini, Oscar M Tirado, Jaume Mora, Enrique de Álava
No abstract text is available yet for this article.
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28667207/a-cluster-randomised-controlled-proof-of-concept-study-to-explore-the-feasibility-and-effect-of-a-patient-directed-intervention-on-quality-of-life-in-patients-with-advanced-soft-tissue-sarcoma
#7
Markus Schuler, Stephan Richter, Gerhard Ehninger, Martin Bornhäuser, Leopold Hentschel
INTRODUCTION: Even with evolving and expanding therapeutical options for the treatment of advanced sarcomas over recent years, the balance between efficacy and toxicity still remains a major concern. Moreover, the symptom burden in patients with sarcoma remains high compared with other malignant diseases. It is, therefore, crucial to assess treatment effectiveness not only in terms of disease-related outcomes (eg, overall survival) but also from an individual and patient-centred perspective using the assessment of patient-reported outcomes (PROs)...
June 30, 2017: BMJ Open
https://www.readbyqxmd.com/read/28651804/efficacy-and-safety-of-trabectedin-or-dacarbazine-in-patients-with-advanced-uterine-leiomyosarcoma-after-failure-of-anthracycline-based-chemotherapy-subgroup-analysis-of-a-phase-3-randomized-clinical-trial
#8
Martee L Hensley, Shreyaskumar R Patel, Margaret von Mehren, Kristen Ganjoo, Robin L Jones, Arthur Staddon, Daniel Rushing, Mohammed Milhem, Bradley Monk, George Wang, Sharon McCarthy, Roland E Knoblauch, Trilok V Parekh, Robert G Maki, George D Demetri
OBJECTIVE: Trabectedin demonstrated significantly improved disease control in leiomyosarcoma and liposarcoma patients in a global phase 3 trial (NCT01343277). A post hoc analysis was conducted to assess the efficacy and safety of trabectedin or dacarbazine in women with uterine leiomyosarcoma (uLMS), the largest subgroup of enrolled patients (40%). METHODS: Of 577 patients randomized 2:1 to receive trabectedin 1.5mg/m(2) by 24-hour IV infusion or dacarbazine 1g/m(2) by 20-120-minute IV infusion once every three weeks, 232 had uLMS (trabectedin: 144; dacarbazine: 88)...
June 23, 2017: Gynecologic Oncology
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
June 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28494349/trabectedin-and-campthotecin-synergistically-eliminate-cancer-stem-cells-in-cell-of-origin-sarcoma-models
#20
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
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