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Trabectedine

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https://www.readbyqxmd.com/read/29656586/prospective-assessment-of-the-predictive-value-of-the-brca1-gene-status-in-sarcoma-patients-treated-with-trabectedin-an-updated-analysis-of-the-eortc-62091-trial
#1
EDITORIAL
Antoine Italiano, Nathan Touati, Saskia Litière, Françoise Collin, Philippe Pourquier, Alessandro Gronchi
We describe the predictive value of BRCA1 gene status on trabectedin efficacy and found no correlation despite the mechanisms of action of this drug that rely on DNA repair systems.
April 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29650688/outcomes-of-elderly-patients-with-advanced-soft-tissue-sarcoma-treated-with-first-line-chemotherapy-a-pooled-analysis-of-12-eortc-soft-tissue-and-bone-sarcoma-group-trials
#2
Eugenie Younger, Saskia Litière, Axel Le Cesne, Olivier Mir, Hans Gelderblom, Antoine Italiano, Sandrine Marreaud, Robin Lewis Jones, Alessandro Gronchi, Winette T A van der Graaf
BACKGROUND: Almost half of patients diagnosed with soft tissue sarcoma (STS) are older than 65 years; however, the outcomes of elderly patients with metastatic disease are not well described. PATIENTS AND METHODS: An elderly cohort of patients aged ≥65 years was extracted from the European Organization for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group database of patients treated with first-line chemotherapy for advanced STS within 12 EORTC clinical trials...
April 12, 2018: Oncologist
https://www.readbyqxmd.com/read/29623421/trabectedin-plus-pegylated-liposomal-doxorubicin-pld-for-patients-with-platinum-sensitive-recurrent-ovarian-cancer-a-prospective-observational-multicenter-study
#3
Ingo B Runnebaum, Dietmar Reichert, Uta Ringsdorf, Markus Kuther, Tobias Hesse, Jalid Sehouli, Pauline Wimberger
PURPOSE: The OVA-YOND study is the first prospective, non-interventional trial designed to evaluate trabectedin (1.1 mg/m2 ) plus PLD (30 mg/m2 ) in patients with platinum-sensitive recurrent ovarian cancer (ROC), given according to the marketing authorization in real-life clinical practice across Germany. METHODS: Eligible patients were adults with platinum-sensitive ROC, pretreated with ≥ 1 platinum-containing regimen/s. The primary endpoint was to assess safety/tolerability of the combination...
April 6, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29552543/cutaneous-angiosarcoma-the-possibility-of-new-treatment-options-especially-for-patients-with-large-primary-tumor
#4
REVIEW
Yasuhiro Fujisawa, Koji Yoshino, Taku Fujimura, Yoshiyuki Nakamura, Naoko Okiyama, Yosuke Ishitsuka, Rei Watanabe, Manabu Fujimoto
The most widely accepted treatment for cutaneous angiosarcoma (CAS) is wide local excision and postoperative radiation to decrease the risk of recurrence. Positive surgical margins and large tumors (T2, >5 cm) are known to be associated with poor prognosis. Moreover, T2 tumors are known to be associated with positive surgical margins. According to previous reports, the majority of CAS patients in Japan had T2 tumors, whereas less than half of the patients in the studies from western countries did so. Consequently, the reported 5-year overall survival of Japanese CAS patients without distant metastasis was only 9%, lower than that for stage-IV melanoma...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29550245/european-organisation-for-research-and-treatment-of-cancer-soft-tissue-and-bone-sarcoma-group-experience-with-advanced-metastatic-epithelioid-sarcoma-patients-treated-in-prospective-trials-clinical-profile-and-response-to-systemic-therapy
#5
N Touati, P Schöffski, S Litière, I Judson, S Sleijfer, W T van der Graaf, A Italiano, N Isambert, T Gil, J Y Blay, D Stark, T Brodowicz, S Marréaud, A Gronchi
AIMS: Epithelioid sarcoma is a soft tissue sarcoma associated with a high rate of local recurrence after wide resection and high incidence of distant metastasis. Little is known about the clinical course and response to systemic treatments in epithelioid sarcoma patients. We carried out a retrospective analysis of clinical data from epithelioid sarcoma patients to provide a reference for the design of future epithelioid sarcoma-specific studies. PATIENTS AND METHODS: Data from patients with epithelioid sarcoma entered in prospective multi-sarcoma phase II/III trials were pooled: EORTC trial 62012 (doxorubicin versus doxorubicin/ifosfamide), 62043 (pazopanib), 62072 (pazopanib versus placebo) and 62091 (doxorubicin versus trabectedin)...
March 15, 2018: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/29546526/hepatoprotective-effect-of-n-acetylcysteine-in-trabectedin-induced-liver-toxicity-in-patients-with-advanced-soft-tissue-sarcoma
#6
Salvatore Grisanti, Deborah Cosentini, Valeria Tovazzi, Susanna Bianchi, Barbara Lazzari, Francesca Consoli, Elisa Roca, Alfredo Berruti, Vittorio D Ferrari
PURPOSE: Trabectedin is one of the few active agents in soft tissue sarcoma (STS) but hepatotoxicity is frequent and represents a dose-limiting factor. Protective strategies aiming at counteracting this important side effect have a crucial clinical impact. Due to its antioxidant properties, N-acetylcysteine (NAC) has a recognized hepatoprotective effect and this provides the rationale for testing NAC in the management of trabectedin-induced hepatotoxicity. METHODS: Patients with recurrent or metastatic soft tissue sarcoma, consecutively observed at our institution, who were considered eligible to trabectedin, received concomitant NAC if they had impaired hepatic or renal function at baseline or developed hepatotoxicity during treatment...
March 15, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29524443/readily-prepared-biodegradable-nanoparticles-to-formulate-poorly-water-soluble-drugs-improving-their-pharmacological-properties-the-example-of-trabectedin
#7
Umberto Capasso Palmiero, Lavinia Morosi, Ezia Bello, Marianna Ponzo, Roberta Frapolli, Cristina Matteo, Mariella Ferrari, Massimo Zucchetti, Lucia Minoli, Marcella De Maglie, Pierpaolo Romanelli, Massimo Morbidelli, Maurizio D'Incalci, Davide Moscatelli
The improvement of the pharmacological profile of lipophilic drug formulations is one of the main successes achieved using nanoparticles (NPs) in medicine. However, the complex synthesis procedure and numerous post-processing steps hamper the cost-effective use of these formulations. In this work, an approach which requires only a syringe to produce self-assembling biodegradable and biocompatible poly(caprolactone)-based NPs is developed. The effective synthesis of monodisperse NPs has been made possible by the optimization of the block copolymer synthesized via a combination of ring opening polymerization and reversible addition-fragmentation chain transfer polymerization...
March 7, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29516254/systemic-treatment-for-adults-with-synovial-sarcoma
#8
REVIEW
Ingrid M E Desar, Emmy D G Fleuren, Winette T A van der Graaf
Synovial sarcoma (SS) is a rare, yet highly malignant, type of soft tissue sarcoma (STS), for which survival has not improved significantly during the past years. In this review, we focus on systemic treatment in adults. Compared to other STS, SS are relatively chemosensitive. Ifosfamide and ifosfamide combinations are active in different lines of treatment. In high-risk extremity and chest wall STS, neoadjuvant doxorubicin and ifosfamide has shown as much activity as high-dose ifosfamide. There are indications that combination chemotherapy with doxorubicin and ifosfamide in this setting improves outcome...
March 7, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29515415/long-lasting-response-to-trabectedin-in-a-patient-with-metastatic-uterine-leiomyosarcoma-a-case-report
#9
Viktoria-Anna Nteli, Wolfgang Knauf, Anja Janton-Klein, Samer El-Safadi
Background: Uterine leiomyosarcoma (uLMS) is a rare tumor that accounts for 1% of all uterine malignancies. In spite of adequate surgical resection of uLMS, even in the early stage, patients remain at high risk for local and distant recurrence. Therefore, the treatment of advanced uLMS represents a considerable challenge. Methods: We report the case of a 47-year-old woman who presented with uLMS with abnormal vaginal bleeding. Results: The patient underwent a total hysterectomy and bilateral adnexectomy, which was followed by 1 year progression-free survival without adjuvant therapy...
January 2018: Case Reports in Oncology
https://www.readbyqxmd.com/read/29515405/metastatic-intimal-sarcoma-of-the-pulmonary-artery-sensitive-to-carboplatin-vinorelbine-chemotherapy-case-report-and-literature-review
#10
Marie Cantaloube, Laurence Moureau-Zabotto, Lena Mescam, Audrey Monneur, Valeria Deluca, Jerome Guiramand, Delphine Perrot, François Bertucci
Pulmonary artery intimal sarcoma (PAIS) is a very rare tumour with a very poor prognosis. In advanced stages, chemotherapy and radiotherapy are poorly efficient, and no standard chemotherapy guideline is currently available. Here, we report on a 37-year-old woman with PAIS initially treated with surgical resection who developed metastatic relapse refractory to anthracycline-based chemotherapy, then trabectedin, then pazopanib. The patient was then given carboplatin-vinorelbine chemotherapy. The treatment was well tolerated, and, rapidly, a CT scan showed an objective response that lasted 8 months despite the 4th therapeutic line...
January 2018: Case Reports in Oncology
https://www.readbyqxmd.com/read/29510410/body-mass-index-as-a-risk-factor-for-toxicities-in-patients-with-advanced-soft-tissue-sarcoma-treated-with-trabectedin
#11
Bruno Vincenzi, Giuseppe Badalamenti, Grazia Armento, Marianna Silletta, Mariella Spalato Ceruso, Giovanna Catania, Andrea Napolitano, Giuseppa Maltese, Sergio Valeri, Lorena Incorvaia, Daniele Santini, Giuseppe Tonini
OBJECTIVES: Low body mass index (BMI) and/or low lean body mass have been shown to be risk factors for chemotherapy-related toxicities in a number of different cancers. However, no data are available regarding the role of BMI as a risk factor for developing toxicities related to the novel anticancer agent, trabectedin, in patients with soft-tissue sarcoma (STS). We evaluated the role of BMI as a risk factor for trabectedin-related toxicity in patients with STS. METHODS: Data from 51 patients with metastatic/advanced STS treated with trabectedin after progression on ≥1 anthracycline ± ifosfamide regimen were retrospectively reviewed...
March 6, 2018: Oncology
https://www.readbyqxmd.com/read/29509592/impact-of-trabectedin-interruption-and-subsequent-rechallenge-on-progression-in-patients-with-advanced-soft-tissue-sarcoma-long-term-follow-up-of-the-t-dis-trial
#12
Nuria Kotecki, Axel Le Cesne, Emmanuelle Tresch-Bruneel, Isabelle Ray-Coquard, Christine Chevreau, François Bertucci, Emilie Bogart, Olivier Mir, Patricia Pautier, Emilie Decoupigny, Stéphanie Clisant, Jean-Yves Blay, Nicolas Penel
OBJECTIVE: To assess the impact of trabectedin rechallenge. PATIENTS AND METHODS: In the T-DIS trial (NCT0130309), after the 6 initial cycles of trabectedin, patients who were free from progressive disease (PD) were randomly assigned either to continuous treatment with trabectedin (C arm) or therapy interruption (I arm). Patients randomized in the interruption arm were allowed to restart trabectedin in case of PD. Herein we report an update of the impact of trabectedin discontinuation after subsequent rechallenge...
March 5, 2018: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29429842/trabectedin-in-ovarian-cancer-is-it-now-a-standard-of-care
#13
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
#14
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-india
#15
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
#16
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
#17
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
#18
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
#19
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...
January 10, 2018: 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
#20
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...
March 2018: Current Opinion in Oncology
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