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Trabectedine

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https://www.readbyqxmd.com/read/28534249/trabectedin-and-eribulin-where-do-they-fit-in-the-management-of-soft-tissue-sarcoma
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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 to CDDP. In the previous 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 treatments significantly inhibited tumor growth compared to untreated control: control (G1): 793...
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
#8
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
#9
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
#10
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
#11
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
#12
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). Hoever, 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
#13
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
#14
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
https://www.readbyqxmd.com/read/28274512/practical-use-and-utility-of-fluorescence-in-situ-hybridization-in-the-pathological-diagnosis-of-soft-tissue-and-bone-tumors
#15
Shintaro Sugita, Tadashi Hasegawa
During routine pathological examination, fluorescence in situ hybridization (FISH) plays a significant role in the genetic analysis of samples. FISH can detect genetic abnormalities such as chromosomal translocations, gene amplifications, and deletions in formalin-fixed, paraffin-embedded (FFPE) specimens. Due to its practical advantages, FISH is already used in many pathology laboratories. It is especially useful for the diagnosis of translocation-related sarcomas (TRSs), which comprise about 25% of soft tissue sarcomas...
March 5, 2017: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
https://www.readbyqxmd.com/read/28260930/update-on-the-role-of-trabectedin-in-the-treatment-of-intractable-soft-tissue-sarcomas
#16
REVIEW
Federica Recine, Alberto Bongiovanni, Nada Riva, Valentina Fausti, Alessandro De Vita, Laura Mercatali, Chiara Liverani, Giacomo Miserocchi, Dino Amadori, Toni Ibrahim
Soft tissue sarcomas (STS) represent a variety of tumors of mesenchymal origin, accounting for about 1% of all adult cancers. This group of tumors comprises over 60 different histotypes with different biology showing different sensitivity to therapeutic agents. For decades, the standard first-line systemic treatment of metastatic STS has comprised anthracycline based-chemotherapy. Second-line therapy options include agents such as ifosfamide, gemcitabine, and pazopanib, but the optimal sequential therapy for the management of metastatic disease has yet to be defined...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28209496/uterine-leiomyosarcoma-epidemiology-contemporary-treatment-strategies-and-the-impact-of-uterine-morcellation
#17
REVIEW
Stephanie Ricci, Rebecca L Stone, Amanda N Fader
Leiomyosarcoma, a rare tumor subtype, accounts for 1% of all uterine malignancies, but contributes to a significant proportion of uterine cancer deaths. Surgery is considered the mainstay of treatment for all soft tissue sarcomas, including uterine variants. However, uterine leiomyosarcoma is challenging to diagnose preoperatively and can mimic the appearance of benign uterine leiomyomas. Recently, concerns have grown in this regard, as surgeons have utilized uterine morcellation and myomectomy procedures unknowingly in the setting of occult uterine sarcoma...
February 13, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28181940/stable-disease-in-a-patient-with-metastatic-leiomyosarcoma-treated-with-trabectedin
#18
Ketty Tavella, Alessandro Villanucci, Laura Vannini, Daniele Lavacchi, Silvia Montelatici, Gianni Amunni, Teresita Mazzei
Leiomyosarcomas represent the most common variant of uterine sarcomas, and are also considered to be the least chemosensitive. To date, adriamycin and ifosfamide are believed to be the most effective drugs for its treatment, in addition to docetaxel and gemcitabine. Recently, the introduction of trabectedin has provided clinicians with another treatment option, and the drug may have some benefits for patients as it may allow for long-term treatment. We present the case of a patient who previously failed multiple cycles of chemotherapy and who was subsequently treated with 30 cycles of trabectedin as third-line therapy for multiple metastases of uterine leiomyosarcoma...
April 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28166781/mechanism-of-action-of-trabectedin-in-desmoplastic-small-round-cell-tumor-cells
#19
S Uboldi, I Craparotta, G Colella, E Ronchetti, L Beltrame, S Vicario, S Marchini, N Panini, G Dagrada, F Bozzi, S Pilotti, C M Galmarini, M D'Incalci, R Gatta
BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive disease, that can be described as a member of the family of small round blue cell tumors. The molecular diagnostic marker is the t(11;22)(p13;q12) translocation, which creates an aberrant transcription factor, EWS-WT1, that underlies the oncogenesis of DSRCT. Current treatments are not very effective so new active drugs are needed. Trabectedin, now used as a single agent for the treatment of soft tissue sarcoma, was reported to be active in some pre-treated DSRCT patients...
February 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28163887/central-venous-access-related-adverse-events-after-trabectedin-infusions-in-soft-tissue-sarcoma-patients-experience-and-management-in-a-nationwide-multi-center-study
#20
Michiel C Verboom, Jan Ouwerkerk, Neeltje Steeghs, Jacob Lutjeboer, J Martijn Kerst, Winette T A van der Graaf, Anna K L Reyners, Stefan Sleijfer, Hans Gelderblom
BACKGROUND: Trabectedin has shown efficacy against soft tissue sarcomas (STS) and has manageable toxicity. Trabectedin is administered through central venous access devices (VAD), such as subcutaneous ports with tunneled catheters, Hickman catheters and PICC lines. Venous access related adverse events are common, but have not yet been reported in detail. METHODS: A retrospective analysis of patient files of STS patients receiving trabectedin monotherapy between 1999 and 2014 was performed in all five STS referral centers in the Netherlands...
2017: Clinical Sarcoma Research
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