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Ruth Pettengell, Bertrand Coiffier, Anton Egorov, Jack Singer, Lilia Sivcheva
BACKGROUND: Pixantrone is recommended in relapsed and refractory non-Hodgkin lymphoma (NHL) or heavily pretreated NHL patients. Its conditional approval in Europe was based on results from the open-label, randomized, phase 3 PIX301 study, comparing pixantrone monotherapy with physician's choice of treatment in 140 patients with relapsed or refractory aggressive NHL. METHODS: This post-hoc analysis of the PIX301 study investigated possible correlations between patient characteristics and clinical response in 17 patients (24%) treated with pixantrone who achieved a complete response (CR) or an unconfirmed complete response (CRu) at study end...
March 21, 2018: Clinical Drug Investigation
Francesco Malaspina, Cinzia Pellegrini, Beatrice Casadei, Lisa Argnani, Pier Luigi Zinzani
Diffuse large B-cell lymphoma is the most frequent histology at diagnosis among non-Hodgkin B lymphomas and can be cured in 50-70% of cases after the first-line chemotherapy regimen. Patients who do not respond to first-line treatment can undergo numerous subsequent steps, culminating in allogeneic stem cell transplant (alloSCT). A relapse after alloSCT, however, carries an awful prognosis, seeing the demise of the patient usually in the following months. Here we present the case of a multiple relapsed patient who successfully underwent therapy with pixantrone after alloSCT, obtaining a complete remission without any considerable side effects...
2017: Acta Haematologica
Giorgio Minotti, Pierantonio Menna, Emanuela Salvatorelli
No abstract text is available yet for this article.
2017: Chemotherapy
Lorena Appio, Carlo Landoni, Maria La Targia, Vanda Bertolli, Martina Chiarucci, Giovanni Crovetti, Elisabetta Vassenna, Giovanni Serio, Marco Bregni
Aggressive non-Hodgkin lymphoma is associated with poor long-term survival after relapse or resistance to chemotherapy. We report a case of aggressive non-Hodgkin lymphoma refractory to first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and second-line R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin) chemotherapy treatments. The patient achieved remission with single-agent pixantrone, and received a consolidation with high-dose BEAM (BCNU, etoposide, cytarabine, and melphalan) chemotherapy and autologous stem cell transplantation...
2017: Chemotherapy
Kamil Piska, Paulina Koczurkiewicz, Adam Bucki, Katarzyna Wójcik-Pszczoła, Marcin Kołaczkowski, Elżbieta Pękala
Anthracycline antibiotics (ANT), such as doxorubicin or daunorubicin, are a class of anticancer drugs that are widely used in oncology. Although highly effective in cancer therapy, their usefulness is greatly limited by their cardiotoxicity. Possible mechanisms of ANT cardiotoxicity include their conversion to secondary alcohol metabolites (i.e. doxorubicinol, daunorubicinol) catalyzed by carbonyl reductases (CBR) and aldo-keto reductases (AKR). These metabolites are suspected to be more cardiotoxic than their parent compounds...
June 2017: Investigational New Drugs
Lajos Gergely
The therapy of lymphomas has undergone a major expansion during the last decade. Novel therapeutic targets have appeared beyond classical chemotherapeutic combinations. These novel drugs have very pronounced action across lymphoma types, and their toxicity profile is usually better tolerable compared to standard chemotherapies. These new therapies are enabling us to offer treatment to those patients who have refractory disease, and we had no option to treat them before these drugs. The author describes several new therapeutic options...
March 8, 2017: Magyar Onkologia
J Félix, B Vandewalle, V Andreozzi, J Almeida, N Silva, C Ferreira, D Ferreira, A Amorim, D Doering, N Branscombe
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Gillian M Keating
Pixantrone (Pixuvri(®)) is an aza-anthracenedione with a novel mode of action that is conditionally approved in the EU for use as monotherapy in adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma (NHL). In the randomized, open-label, multinational, phase 3 PIX301 trial in patients with multiply relapsed or refractory aggressive NHL, the complete response (CR) plus unconfirmed CR (uCR) rate at the end of treatment (primary endpoint) was significantly higher with intravenous pixantrone monotherapy than with a single-agent comparator (vinorelbine, oxaliplatin, ifosfamide, etoposide, mitoxantrone or gemcitabine)...
October 2016: Drugs
Pierantonio Menna, Emanuela Salvatorelli, Giorgio Minotti
Pixantrone (6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione) has been approved by the European Medicines Agency for the treatment of refractory or relapsed non-Hodgkin's lymphoma (NHL). It is popularly referred to as a novel aza-anthracenedione, and as such it is grouped with anthracycline-like drugs. Preclinical development of pixantrone was in fact tailored to retain the same antitumor activity as that of anthracyclines or other anthracenediones while also avoiding cardiotoxicity that dose-limits clinical use of anthracycline-like drugs...
August 15, 2016: Chemical Research in Toxicology
Shyam K Konda, Celine Kelso, Paul P Pumuye, Jelena Medan, Brad E Sleebs, Suzanne M Cutts, Don R Phillips, J Grant Collins
The ability of a bis-amino mitoxantrone anticancer drug (named WEHI-150) to form covalent adducts with DNA, after activation by formaldehyde, has been studied by electrospray ionisation mass spectrometry and HPLC. Mass spectrometry results showed that WEHI-150 could form covalent adducts with d(ACGCGCGT)2 that contained one, two or three covalent links to the octanucleotide, whereas the control drugs (daunorubicin and the anthracenediones mitoxantrone and pixantrone) only formed adducts with one covalent link to the octanucleotide...
May 18, 2016: Organic & Biomolecular Chemistry
Pier Luigi Zinzani, Paolo Corradini, Maurizio Martelli, Giorgio Minotti, Stefano Oliva, Michele Spina, Giovanni Barosi, Sante Tura
OBJECTIVES: In this paper, we present a review of critical concepts and research perspectives and produce recommendations on the optimal use of pixantrone in non-Hodgkin lymphoma (NHL) by group discussion from an expert panel appointed by the Italian Society of Hematology and the affiliate societies, Società Italiana di Ematologia Sperimentale and Gruppo Italiano Trapianto di Midollo Osseo. METHODS: Recommendations were produced using the Delphi process. Scientific evidence on pixantrone efficacy was analyzed using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology in the areas where at least one randomized trial was published...
December 2016: European Journal of Haematology
Ruth Pettengell, Catherine Sebban, Pier Luigi Zinzani, Hans Gunter Derigs, Sergey Kravchenko, Jack W Singer, Panteli Theocharous, Lixia Wang, Mariya Pavlyuk, Kahina M Makhloufi, Bertrand Coiffier
This post hoc analysis of a phase 3 trial explored the effect of pixantrone in patients (50 pixantrone, 47 comparator) with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL) confirmed by centralized histological review. Patients received 28-d cycles of 85 mg/m(2) pixantrone dimaleate (equivalent to 50 mg/m(2) in the approved formulation) on days 1, 8 and 15, or comparator. The population was subdivided according to previous rituximab use and whether they received the study treatment as 3rd or 4th line...
September 2016: British Journal of Haematology
David Belada, Pencho Georgiev, Shaker Dakhil, Lowell F Inhorn, David Andorsky, J Thaddeus Beck, Donald Quick, Ruth Pettengell, Robert Daly, James P Dean, Mariya Pavlyuk, Nelly Failloux, Kai Hübel
UNLABELLED: We describe the rationale and design of the ongoing randomized, active-controlled, multicenter, Phase III study evaluating the efficacy of pixantrone and rituximab versus gemcitabine and rituximab in patients with diffuse large B-cell lymphoma or follicular grade 3 lymphoma, who are ineligible for high-dose chemotherapy and stem cell transplantation, and who failed front-line regimens containing rituximab. The administration schedule is pixantrone 50 mg/m(2) intravenously (iv...
August 2016: Future Oncology
Boyd M Koffman, Miles Hacker, William T Gunning, Anthony Quinn
OBJECTIVE: This study aimed to present anthracenedione agents that have been used to treat multiple sclerosis (MS), problems related to their use, and knowledge gained from our experiences using these agents to develop more efficacious drugs with fewer adverse effects. METHODS: We review preclinical and clinical data during the development mitoxantrone, an anthracycline, for the treatment of MS; benefits and potential risks; and strategies to reduce complications of anthracyclines...
March 2016: Clinical Neuropharmacology
Toby A Eyre, Kim M Linton, Phillipa Rohman, Jaimal Kothari, Kate Cwynarski, Kirit Ardeshna, Chris Bailey, Wendy L Osborne, Clare Rowntree, Dewi Eden, Paneesha Shankara, David W Eyre, Parag Jasani, Aristeidis Chaidos, Graham P Collins, Chris S Hatton
Relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in those unfit or ineligible for autologous stem cell transplantation is associated with a poor outcome and new treatment approaches are needed. Pixantrone is a novel aza-anthracenedione which is structurally similar to anthracyclines and is licenced in R/R DLBCL and National Institute for Health and Care Excellence (NICE)-approved following the PIX301 trial. No data exist post-NICE approval. We performed a UK-wide retrospective multi-centre study of 92 R/R DLBCL who received pixantrone...
June 2016: British Journal of Haematology
Noemi Muszbek, Ananth Kadambi, Tereza Lanitis, Anthony J Hatswell, Dilip Patel, Lixia Wang, Jack W Singer, Ruth Pettengell
PURPOSE: Aggressive non-Hodgkin's lymphoma (aNHL) is associated with poor long-term survival after relapse, and treatment is limited by a lack of consensus regarding standard of care. Pixantrone was studied in a randomized trial in patients with relapsed or refractory aNHL who had failed ≥ 2 lines of therapy, demonstrating a significant improvement in complete or unconfirmed complete response and progression-free survival (PFS) compared with investigators' choice of single-agent therapy...
March 2016: Clinical Therapeutics
Brian B Hasinoff, Xing Wu, Daywin Patel, Ragu Kanagasabai, Soumendrakrishna Karmahapatra, Jack C Yalowich
Pixantrone is a new noncardiotoxic aza-anthracenedione anticancer drug structurally related to anthracyclines and anthracenediones, such as doxorubicin and mitoxantrone. Pixantrone is approved in the European Union for the treatment of relapsed or refractory aggressive B cell non-Hodgkin lymphoma. This study was undertaken to investigate both the mechanism(s) of its anticancer activity and its relative lack of cardiotoxicity. Pixantrone targeted DNA topoisomerase IIα as evidenced by its ability to inhibit kinetoplast DNA decatenation; to produce linear double-strand DNA in a pBR322 DNA cleavage assay; to produce DNA double-strand breaks in a cellular phospho-histone γH2AX assay; to form covalent topoisomerase II-DNA complexes in a cellular immunodetection of complex of enzyme-to-DNA assay; and to display cross-resistance in etoposide-resistant K562 cells...
February 2016: Journal of Pharmacology and Experimental Therapeutics
Raphael Koch, Thiha Aung, Daniel Vogel, Bjoern Chapuy, Dirk Wenzel, Sabrina Becker, Ursula Sinzig, Vivek Venkataramani, Tobias von Mach, Ralf Jacob, Lorenz Truemper, Gerald G Wulf
PURPOSE: Although R-CHOP-based immunochemotherapy cures significant proportions of patients with aggressive B-cell lymphoma, tumor cell susceptibility to chemotherapy varies, with mostly fatal outcome in cases of resistant disease. We and others have shown before that export of cytostatic drugs contributes to drug resistance. Now we provide a novel approach to overcome exosome-mediated drug resistance in aggressive B-cell lymphomas. EXPERIMENTAL DESIGN: We used well-established centrifugation protocols to purify exosomes from DLBCL cell lines and detected anthracyclines using FACS and HPLC...
January 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Richard Gonsette, Marc Debouverie, Christian Sindic, Jean-Christophe Ferré, Gilles Edan
BACKGROUND: Mitoxantrone has been approved for patients with worsening relapsing-remitting (RR) or secondary progressive multiple sclerosis (SPMS), but its long-term use is limited by its cardiotoxicity. Pixantrone (PIX) is an analog of mitoxantrone. OBJECTIVES: The aim of this open-label, multicenter, noncomparative Phase I/II trial was to explore the immunosuppressive effect of PIX, its impact on clinical disease activity and cerebral gadolinium-enhanced (Gd(+)) lesions, and its safety...
May 2016: Multiple Sclerosis: Clinical and Laboratory Research
Neil Beeharry, Andrea Ghelli Luserna Di Rora, Mitchell R Smith, Timothy J Yen
Pixantrone is a novel aza-anthracenedione active against aggressive lymphoma and is being evaluated for use against various hematologic and solid tumors. The drug is an analog of mitoxantrone, but displays less cardiotoxicity than mitoxantrone or the more commonly used doxorubicin. Although pixantrone is purported to inhibit topoisomerase II activity and intercalate with DNA, exact mechanisms of how it induces cell death remain obscure. Here we evaluated the effect of pixantrone on a panel of solid tumor cell lines to understand its mechanism of cell killing...
2015: Cancer Biology & Therapy
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