How to Manage Acute Promyelocytic Leukemia
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A Systematic Review of the Effectiveness of Docetaxel and Mitoxantrone for the Treatment of Metastatic Hormone-Refractory Prostate Cancer
British Journal of Cancer (2006) 95, 457 – 462 & 2006 Cancer Research UK All rights reserved 0007 – 0920/06 $30.00 www.bjcancer.com A systematic review of the effectiveness of docetaxel and mitoxantrone for the treatment of metastatic hormone-refractory prostate cancer *,1 1 1 1 2 3 4 5 R Collins , R Trowman , G Norman , K Light , A Birtle , E Fenwick , S Palmer and R Riemsma 1 2 Centre for Reviews and Dissemination, University of York, Heslington, York YO10 5DD, UK; Rosemere Cancer Centre, Royal Preston Hospital, Sharoe 3 Green Lane North, Fulwood, Preston PR2 9HT, UK; Public Health & Health Policy, Division of Community Based Sciences, University of Glasgow, 4 5 1 Lilybank Gardens, Glasgow G12 8RZ, UK; Centre for Health Economics, University of York, Heslington, York YO10 5DD, UK; Kleijnen Systematic Reviews Ltd, Westminster Business Centre, 10 Great North Way, Nether Poppleton, York YO26 6RB, UK Clinical Studies A systematic review was performed to evaluate the clinical effectiveness of docetaxel in combination with prednisolone (docetaxel is licensed in the UK for use in combination with prednisone or prednisolone for the treatment of patients with metastatic hormone- refractory prostate cancer. Prednisone is not used in the UK, but it is reasonable to use docetaxel plus prednisone data in this review of docetaxel plus prednisolone) for the treatment of metastatic hormone-refractory prostate cancer. A scoping search identified a trial of docetaxel plus prednisone vs mitoxantrone plus prednisone, but did not identify any trials comparing docetaxel plus prednisolone/prednisone with any other treatments. Therefore, we considered additional indirect evidence that would enable a comparison of docetaxel plus prednisolone/prednisone with other chemotherapy regimens and active supportive care. -
Mitomycin C: Indications for Use and Safe Practice in Ophthalmology Published by American Society of Ophthalmic Registered Nurses
Mitomycin C: Indications for Use and Safe Practice in Ophthalmology Published by American Society of Ophthalmic Registered Nurses Editor Susan Clouser, RN, MSN, CRNO American Society of Ophthalmic Registered Nurses 655 Beach Street, San Francisco, CA 94109 1 This publication includes independent authors’ guidelines for the safe use and handling of mitomycin C in ophthalmic practices. Readers should use these guidelines as a resource only. These guidelines should never take precedence over manufacturers’ recommended practices, facilities policies and procedures, or compliance with federal regulations. Information in this publication may assist facilities in developing policies and procedures specifc to their needs and practice environment. American Society of Ophthalmic Registered Nurses For questions regarding content or association issues contact ASORN at [email protected] or 1.415.561.8513. Copyright © 2011 by American Society of Ophthalmic Registered Nurses American Society of Ophthalmic Registered Nurses has the exclusive rights to reproduce this work, to prepare derivative works from this work, to publicly distribute this work, to publicly perform this work and to publicly display this work. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of American Society of Ophthalmic Registered Nurses. Printed in the United States of America 10 9 8 7 6 5 4 3 2 1 ACKNOWLEDGMENTS The development of this educational resource would not have been possible without the knowledge and expertise of the ophthalmologists and ophthalmic registered nurses who wrote the content and the subsequent reviewers who provided valuable input. -
NOVANTRONE (Mitoxantrone for Injection Concentrate) in Patients with Hepatic Insufficiency Is Not Established (See CLINICAL PHARMACOLOGY)
NOVANTRONE® mitoXANTRONE for injection concentrate WARNING NOVANTRONE® (mitoxantrone for injection concentrate) should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents. NOVANTRONE® should be given slowly into a freely flowing intravenous infusion. It must never be given subcutaneously, intramuscularly, or intra-arterially. Severe local tissue damage may occur if there is extravasation during administration. (See ADVERSE REACTIONS, General, Cutaneous and DOSAGE AND ADMINISTRATION, Preparation and Administration Precautions). NOT FOR INTRATHECAL USE. Severe injury with permanent sequelae can result from intrathecal administration. (See WARNINGS, General) Except for the treatment of acute nonlymphocytic leukemia, NOVANTRONE® therapy generally should not be given to patients with baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving NOVANTRONE®. Cardiotoxicity: Congestive heart failure (CHF), potentially fatal, may occur either during therapy with NOVANTRONE® or months to years after termination of therapy. Cardiotoxicity risk increases with cumulative NOVANTRONE dose and may occur whether or not cardiac risk factors are present. Presence or history of cardiovascular disease, radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or use of other cardiotoxic drugs may increase this risk. In cancer patients, the risk of symptomatic CHF was estimated to be 2.6% for patients receiving up to a cumulative dose of 140 mg/m2. To mitigate the cardiotoxicity risk with NOVANTRONE, prescribers should consider the following: NOVANTRONE mitoXANTRONE for injection 1 All Patients: - All patients should be assessed for cardiac signs and symptoms by history, physical examination, and ECG prior to start of NOVANTRONE® therapy. -
DRUG NAME: Thioguanine
Thioguanine DRUG NAME: Thioguanine SYNONYM(S): 2-amino-6-mercaptopurine,1 6-TG, TG COMMON TRADE NAME(S): LANVIS® CLASSIFICATION: antimetabolite, cytotoxic2 Special pediatric considerations are noted when applicable, otherwise adult provisions apply. MECHANISM OF ACTION: Thioguanine is a purine antagonist.1 It is a pro-drug that is converted intracellullarly directly to thioguanine monophosphate3 (also called 6-thioguanylic acid)4 (TGMP) by the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT). TGMP is further converted to the di- and triphosphates, thioguanosine diphosphate (TGDP) and thioguanosine triphosphate (TGTP).5 The cytotoxic effect of thioguanine is a result of the incorporation of these nucleotides into DNA. Thioguanine has some immunosuppressive activity.1 Thioguanine is specific for the S phase of the cell cycle.6 PHARMACOKINETICS: Oral Absorption • incomplete and variable (14-46%)7 • preferably taken on an empty stomach8; may be taken with food if needed • children9: <20% Distribution crosses the placenta10 cross blood brain barrier? negligible11 volume of distribution12 148 mL/kg plasma protein binding no information found Metabolism hepatic10 activation by4: • hypoxanthine-guanine phosphoribosyl transferase (HGPRT) elimination by4: • guanase to 6-thioxanthine • thiopurine methyltransferase (TPMT) to 2-amino-6-methyl thiopurine active metabolites3,4 thiopurine nucleotides inactive metabolites4 6-thioxanthine, 2-amino-6-methyl thiopurine Excretion renal excretion12; initially intact drug, then metabolites urine12 -
Severe Myelotoxicity Associated with Thiopurine S-Methyltransferase*3A
Case Report DOI: 10.4274/tjh.2013.0082 Severe Myelotoxicity Associated with Thiopurine S-Methyltransferase*3A/*3C Polymorphisms in a Patient with Pediatric Leukemia and the Effect of Steroid Therapy Pediatrik Bir Lösemi Olgusunda Tiyopurin S-Metiltransferaz *3A/*3C Polimorfizmi ile İlişkili Ağır Miyelotoksisite-Steroid Tedavisinin Etkisi Burcu Fatma Belen1, Türkiz Gürsel1, Nalan Akyürek2, Meryem Albayrak3, Zühre Kaya1, Ülker Koçak1 1Gazi University Faculty of Medicine, Department of Pediatric Hematology, Ankara, Turkey 2Gazi University Faculty of Medicine, Department of Pathology, Ankara, Turkey 3Kırıkkale University Faculty of Medicine, Department of Pediatric Hematology, Ankara, Turkey Abstract: Myelosuppression is a serious complication during treatment of acute lymphoblastic leukemia and the duration of myelosuppression is affected by underlying bone marrow failure syndromes and drug pharmacogenetics caused by genetic polymorphisms. Mutations in the thiopurine S-methyltransferase (TPMT) gene causing excessive myelosuppression during 6-mercaptopurine (MP) therapy may cause excessive bone marrow toxicity. We report the case of a 15-year-old girl with T-ALL who developed severe pancytopenia during consolidation and maintenance therapy despite reduction of the dose of MP to 5% of the standard dose. Prednisolone therapy produced a remarkable but transient bone marrow recovery. Analysis of common TPMT polymorphisms revealed TPMT *3A/*3C. Key Words: Myelosuppression, Thiopurine S-methyl transferase, Acute leukemia Özet: Miyelosupresyon, -
List of Drugs Not Repackaged by Safecor Health
Drugs Not Repackaged by Safecor Health The following tables list specific medications that are not repackaged by Safecor Health due to regulatory restrictions or specific manufacturer requirements. The items not repackaged are alphabetically listed below, both by brand name (table 1) and generic name (table 2). Please note: Safecor Health cannot repackage any beta lactam antibiotics (such as penicillins, amoxicillin and cephalosporins) or potent chemotherapeutic agents. Also, due to FDA restrictions, we cannot repackage half- or quarter-tabs, compounded or diluted drugs, powders, and ointments or creams. Safecor Health can repackage most hazardous drugs on the NIOSH list. Contact us for a complete list of hazardous drugs repackaged by Safecor Health. Table 1. Do Not Repackage Drugs Sorted Alphabetically by Brand Name Brand Name(s) Generic Name(s) Reason Item Cannot Be Repackaged Adrucil Fluorouracil Potent chemotherapy agent Aspirin and Extended-Release Specific manufacturer recommendations for very Aggrenox Dipyridamole limited expiration dating Albenza Albendazole Cost per dose prohibitive Alkeran Melphalan Potent chemotherapy agent Augmentin Amoxicillin and Clavulanate Potassium Safecor Health does not repackage this drug class Manufacturer states, "dispense in original container," Belsomra Suvorexant on the drug label Manufacturer states, "dispense in original container," Biktarvy Bictegravir, Emtricitabine and Tenofovir Alafenamide on the drug label Bion Tears Dextran, Hypromellose Ophthalmic Drops Sterile and unpreserved CeeNU Lomustine -
Methotrexate Cross-Resistance in a Mitoxantrone-Selected Multidrug-Resistant MCF7 Breast Cancer Cell Line Is Attributable to Enhanced Energy-Dependent Drug Efflux1
[CANCER RESEARCH 60, 3514–3521, July 1, 2000] Methotrexate Cross-Resistance in a Mitoxantrone-selected Multidrug-resistant MCF7 Breast Cancer Cell Line Is Attributable to Enhanced Energy-dependent Drug Efflux1 Erin L. Volk, Kristin Rohde, Myung Rhee, John J. McGuire, L. Austin Doyle, Douglas D. Ross, and Erasmus Schneider2 Wadsworth Center, New York State Department of Health, Albany, New York 12201 [E. L. V., K. R., M. R., E. S.]; Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, New York 12201 [E. L. V., E. S.]; Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263 [J. J. M.]; Greenbaum Cancer Center of the University of Maryland, Baltimore, Maryland 21201 [L. A. D., D. D. R.]; Department of Medicine, Division of Hematology/Oncology, University of Maryland School of Medicine, Baltimore, Maryland 21201 [L. A. D., D. D. R.]; and Baltimore Veterans Medical Center, Department of Veterans Affairs, Baltimore, Maryland 21201 [D. D. R.] ABSTRACT resistance has been shown to be caused by decreased uptake attribut- able to the absence (2) of or defects (5, 6) in RFC1, reduced poly- Cellular resistance to the antifolate methotrexate (MTX) is often caused glutamylation either through decreased FPGS activity and/or expres- by target amplification, uptake defects, or alterations in polyglutamyla- sion (7), or enhanced ␥-GH activity and/or expression (8), and DHFR tion. Here we have examined MTX cross-resistance in a human breast carcinoma cell line (MCF7/MX) selected in the presence of mitoxantrone, overexpression (9) or mutation (10–12). an anticancer agent associated with the multidrug resistance (MDR) In contrast, a putative role for drug efflux in MTX resistance, phenotype. -
Cellular Pharmacology of Mitoxantrone in P
Leukemia (1997) 11, 2066–2074 1997 Stockton Press All rights reserved 0887-6924/97 $12.00 Cellular pharmacology of mitoxantrone in p-glycoprotein-positive and -negative human myeloid leukemic cell lines U Consoli, NT Van, N Neamati, R Mahadevia, M Beran, S Zhao and M Andreeff Department of Hematology, Section of Experimental Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Previous reports suggest that resistance to mitoxantrone in dif- protein is particularly important because it confers cross-resist- ferent tumor cell lines is unrelated to the overexpression of p- ance to several structurally unrelated drugs.9 The mechanisms glycoprotein. In order to determine the role of p-glycoprotein in the cellular pharmacology of mitoxantrone flow cytometry of action of mitoxantrone resistance are not well known. and confocal microscopy were used to study two human Although mitoxantrone seems to select for a unique drug- myeloid leukemia cell lines selected for resistance to mitoxan- resistance phenotype, some cross-resistance with anthracy- trone (HL-60MX2) and doxorubicin (HL-60DOX). To optimize the clines has been shown in vitro.10,11 Human colon carci- detection of intracellular mitoxantrone, we determined the noma,12 leukemia13 and gastric carcinoma14 cell lines selec- maximum excitation (607 nm) and emission (684 nm) wave- length by fluorescence spectroscopy. The modified flow cyto- ted by continuous exposure to increasing concentrations of metric conditions using 568.2 nm laser emission for excitation mitoxantrone had no p-glycoprotein overexpression. Clinical and a 620 nm long pass filter for fluorescence collection cross-over studies have not demonstrated complete cross- resulted in a 1-log increase in sensitivity, compared with stan- resistance between mitoxantrone and doxorubicin,15,16 pro- dard 488-nm laser excitation. -
Immunomodulators
Fact Sheet News from the IBD Help Center IMMUNOMODULATORS Medical treatment for Crohn’s disease and ulcerative colitis has two main goals: achieving remission (control or resolution of inflammation leading to symptom resolution with healing of the inflamed tissue) and then maintaining remission. To accomplish these goals, treatment is aimed at controlling the ongoing inflammation in the intestine—the cause of inflammatory bowel disease (IBD) symptoms. As the name implies, immunomodulators modify the activity of the immune system, in turn, decreasing the inflammatory response. Immunomodulators are most often used in organ transplantation to prevent rejection of the new organ as well as in autoimmune diseases such as rheumatoid arthritis. Since the late 1960s, they have also been used to treat people with IBD, where the normal regulation of the immune system is affected. Immunomodulators, by themselves or with another agent, may be appropriate in the following treatment situations: • Nonresponse or intolerance to aminosalicylates, antibiotics, or corticosteroids • Steroid-dependent disease or frequent need for steroids • Perianal (around the anus) disease that does not respond to antibiotics • Fistulas (abnormal channels between two loops of intestine, or between the intestine and another structure—such as the skin) • To bolster or optimize the effect of a biologic drug and prevent the development of resistance to biologic drugs • To prevent recurrence after surgery Because it can take up to three to six months to see an improvement in symptoms with immunomodulators, steroids may be started at the same time to produce a faster response. Lower doses of the steroid may be utilized in some cases, producing fewer side effects. -
Single-Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Durable Remissions with Minimal Toxicity
CLINICAL TRIALS AND OBSERVATIONS Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity Vikram Mathews, Biju George, Kavitha M. Lakshmi, Auro Viswabandya, Ashish Bajel, Poonkuzhali Balasubramanian, Ramachandran Velayudhan Shaji, Vivi M. Srivastava, Alok Srivastava, and Mammen Chandy Arsenic trioxide, as a single agent, has of 25 months (range: 8-92 months), the men was administered on an outpatient proven efficacy in inducing molecular remis- 3-year Kaplan-Meier estimate of EFS, DFS, basis. Single-agent As2O3, as used in this -sion in patients with acute promyelocytic and OS was 74.87% ؎ 5.6%, 87.21% ؎ series, in the management of newly diag leukemia (APL). There is limited long- 4.93%, and 86.11% ؎ 4.08%, respectively. nosed cases of APL, is associated with term outcome data with single-agent Patients presenting with a white blood responses comparable with conventional As O in the management of newly diag- cell (WBC) count lower than 5 ؋ 109/L and chemotherapy regimens. Additionally, this 2 3 nosed cases of APL. Between January a platelet count higher than 20 ؋ 109/L at regimen has minimal toxicity and can be have an excel- administered on an outpatient basis after ([%30.6] 22 ؍ to December 2004, 72 newly diag- diagnosis (n 1998 nosed cases of APL were treated with a lent prognosis with this regimen (EFS, remission induction. (Blood. 2006;107: regimen of single-agent As2O3 at our cen- OS, and DFS of 100%). The toxicity pro- 2627-2632) ter. Complete hematologic remission was file, in the majority, was mild and revers- achieved in 86.1%. -
Acute Lymphoblastic Leukemia (ALL) (Part 1 Of
LEUKEMIA TREATMENT REGIMENS: Acute Lymphoblastic Leukemia (ALL) (Part 1 of 12) Note: The National Comprehensive Cancer Network (NCCN) Guidelines® for Acute Lymphoblastic Leukemia (ALL) should be consulted for the management of patients with lymphoblastic lymphoma. Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. They are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any -
Innovative Design of Early Phase Clinical Trials in Radiation Oncology
Integration of chemotherapy and radiation therapy Adam P. Dicker, M.D., Ph.D. Chair, Department of Radiation Oncology Kimmel Cancer Center Jefferson Medical College of Thomas Jefferson University Philadelphia, PA No Disclosures 2 U.S. Cancer Statistics - 1998 1.2 Million New Cases Each Year 600,000 600,000 Localized Disseminated Tumors Tumors 570,000 Cured 70,000 Cured Via Surgery or Via Radiotherapy Chemotherapy Outline • Current Status • Rationale for combination of chemotherapy with Radiation • Mechanism of action and resistance • Disease sites and toxicity of combination therapies • New targets 4 The past decade • Radiotherapy has Improved & will Improve Further • Most Recent Advances Relate to Imaging & Planning • Future Advances will be in New Delivery Approaches • RT Dose and Fractionation Paradigms will Shift • RT Target Volume “Rules” will Also Shift • RT/Drug Interactions Could Dictate Dose & Fractionation Therapeutic Ratio Curves Reasons to use Chemoradiation • Sterilize micrometastases outside of the XRT portal • Tumor cell sensitization • Improved nutrition and reoxygenation to hypoxic tumor cell (decrease tumor burden) – Better blood supply to remaining tumor cells • Cells cycle into a more radiation sensitive phase • Inhibit cell division between radiation doses • Inhibit cellular repair of damage between therapies Rationale for combined chemotherapy and radiotherapy • Spatial cooperation • Toxicity independence • Action as a radiosensitizer (possible synergism) • Eliminate need for surgical procedure. – Not all patients