DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 9,545.449 B2 Krantz (45) Date of Patent: Jan

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 9,545.449 B2 Krantz (45) Date of Patent: Jan USOO9545449B2 (12) United States Patent (10) Patent No.: US 9,545.449 B2 Krantz (45) Date of Patent: Jan. 17, 2017 (54) SITE-SPECIFIC LABELING AND TARGETED 8,030.459 B2 10/2011 Papisov et al. DELIVERY OF PROTEINS FOR THE 8,927.485 B2 1/2015 Krantz et al. 2003/0215877 A1 11/2003 Love et al. TREATMENT OF CANCER 2005, 00792O8 A1 4/2005 Albani 2007, 0123465 A1 5/2007 Adermann et al. (71) Applicant: Advanced Proteome Therapeutics 2010.0099649 A1* 4/2010 Krantz et al. ................. 514f131 Inc., Boston, MA (US) 2011 0002978 A1 1/2011 Harrison 2011/0263832 A1 10/2011 Krantz et al. (72) Inventor: Alexander Krantz, Boston, MA (US) 2013,0165382 A1 6/2013 Krantz et al. (73) Assignee: Advanced Proteone Therapeutics Inc., FOREIGN PATENT DOCUMENTS Boston, MA (US) WO WO-89/11867 A1 12/1989 WO WO-02/42427 A2 5, 2002 (*) Notice: Subject to any disclaimer, the term of this WO WO-O2/O87497 A2 11/2002 patent is extended or adjusted under 35 WO WO-03/093478 A1 11, 2003 U.S.C. 154(b) by 0 days. WO WO-2007 112362 A2 10, 2007 WO WO-2010, 140886 A1 12/2010 (21) Appl. No.: 14/400,190 WO WO-2011, 153250 A2 12/2011 (22) PCT Filed: May 13, 2013 OTHER PUBLICATIONS (86). PCT No.: PCT/US2O13/040823 Yu et al. Site-specific crosslinking of annexin proteins by 1.4- benzoquinone: a novel crosslinker for the formation of protein S 371 (c)(1), dimers and diverse protein conjugates (Org. Biomol. Chem..., 2012, (2) Date: Nov. 10, 2014 10, 4500).* Blanco-Canosa et al., “An efficient Fmoc-SPPS approach for the (87) PCT Pub. No.: WO2013/170272 generation of thioester peptide precursors for use in native chemical PCT Pub. Date: Nov. 14, 2013 ligation.” Angew Chem Int Ed Engl. 47(36):6851-5 (2008) (10 pages). (65) Prior Publication Data Brandt et al., "Covalent attachment of proteins to polysaccharide carriers by means of benzoquinone.” Biochim Biophys Acta. US 2015/02O2314 A1 Jul. 23, 2015 386(1): 196-202 (1975). Deady et al., “Synthesis and antitumor activity of Some indeno1,2- Related U.S. Application Data bduinoline-based bis carboxamides.” Bioorg Med Chem. 8(5):977 84 (2000). (60) Provisional application No. 61/849,034, filed on Jan. Dixon, “N-terminal modification of proteins—A review.” J Protein 17, 2013, provisional application No. 61/848,601, Chem. 3(1):99-108 (1984). filed on Jan. 7, 2013, provisional application No. Gentle et al., “Direct production of proteins with N-terminal cys 61/741,984, filed on Aug. 1, 2012, provisional teine for site-specific conjugation.” Bioconjug Chem. 15(3):658-63 application No. 61/688,308, filed on May 11, 2012. (2004). Hauser et al., “Expressed protein ligation using an N-terminal (51) Int. Cl. cysteine containing fragment generated in vivo from a pelB fusion A6 IK 38/00 (2006.01) protein.” Protein Expr Purif. 54(2):227-33 (2007) (13 pages). A6 IK 47/48 (2006.01) International Preliminary Report on Patentability and Written Opin A6 IK 38/17 (2006.01) ion for International Patent Application No. PCT/US2013/040823, A6 IK 38/38 (2006.01) issued Nov. 11, 2014 (15 pages). A6 IK 38/40 (2006.01) (Continued) A6 IK 45/06 (2006.01) C07K I4/435 (2006.01) (52) U.S. Cl. Primary Examiner — James H Alstrum Acevedo CPC ......... A61K 47/48246 (2013.01); A61K 38/17 Assistant Examiner — Sergio Coffa (2013.01); A61K 38/38 (2013.01); A61K 38/40 (74) Attorney, Agent, or Firm — Clark & Elbing LLP (2013.01); A61K 45/06 (2013.01); C07K 14/435 (2013.01) (58) Field of Classification Search (57) ABSTRACT None The present invention relates to the formation of protein See application file for complete search history. conjugates from proteins chemically modified for linkage to (56) References Cited (1) anticancer drug pharmacophores, (2) ligands to biomark ers on cancer cell Surfaces, (3) and/or another protein U.S. PATENT DOCUMENTS molecule. It provides and specifies new compositions, meth 5,900.404 A 5/1999 Gegg et al. ods and combinations for tumor, and tumor vasculature 6,017,876 A 1/2000 Gegg et al. targeting and cancer treatment. 6,204.247 B1 3/2001 Gegg et al. 6,326,468 B1 12/2001 Canne et al. 6.420,340 B2 7/2002 Gegg et al. 16 Claims, No Drawings US 9,545.449 B2 Page 2 (56) References Cited Radic et al., “Probing gorge dimensions of cholinesterases by freeze-frame click chemistry.” Chem Biol Interact. 175(1-3):161-5 (2008) (10 pages). OTHER PUBLICATIONS Rice et al., “Inhibitors of HIV nucleocapsid protein zinc fingers as candidates for the treatment of AIDS,” Science. 270(5239): 1194-7 International Search Report for International Patent Application No. (1995). PCT/US 13/40823, mailed Dec. 16, 2013 (8 pages). Selden et al., “Cross-linked dimers with nucleating activity in actin Johnson et al., “Insights into the mechanism and catalysis of the prepared from muscle acetone powder,” Biochemistry. 39(1):64-74 native chemical ligation reaction.” JAm ChemSoc. 128(20):6640-6 (2000). (2006). Sunde et al., “Improved conditions for the removal of 2-oxoacyl Kalia et al., “Hydrolytic stability of hydrazones and groups from the N-terminus of proteins,” Biochim Biophys Acta. oximes.” Angew Chem Int Ed Engl. 47(39):7523-6 (2008). 1388(1):45-52 (1998). Kent, “Total chemical synthesis of proteins,” Chem Soc Rev. Tam et al., “Orthogonal ligation strategies for peptide and protein.” 38(2):338-51 (2009). Biopolymers. 51(5):311-32 (1999). Kolb et al., “Click chemistry: diverse chemical function from a few Wang et al., “Interaction of a self-assembling peptide with oligo good reactions.” Angew Chem Int Ed. 40(11):2004-21 (2001). nucleotides: complexation and aggregation,” Biophys J. Lo Conte et al., “Photoinduced addition of glycosylthiols to alkynyl 93(7):2477-90 (2007). peptides: use of free-radical thiol-yne coupling for post-translational Wen et al., “Erythropoietin structure-function relationships: high double-glycosylation of peptides,” J Org Chem. 75(13):4644-7 degree of sequence homology among mammals,” Blood. (2010). 82(5): 1507-16 (1993). Loo et al., "Biophysical characterization of zinc ejection from HIV Witus et al., “Identification of highly reactive sequences for PLP nucleocapsid protein by anti-HIV 2,2'-dithiobisbenzamides and mediated bioconjugation using a combinatorial peptide library,” J benzisothiazolones,” J Med Chem. 39(21):4313-20 (1996). Am ChemSoc. 132(47): 16812-7 (2010) (14 pages). Niemeyer et al., “Oligonucleotide-directed self-assembly of pro Extended European Search Report for European Application No. teins: semisynthetic DNA-streptavidin hybrid molecules as con 13787738.7, mailed Jul. 29, 2016 (17 pages). nectors for the generation of macroscopic arrays and the construc Liet al., “Site-specific labeling of annexin V with F-18 for apoptosis tion of Supramolecular bioconjugates. Nucleic Acids Res. imaging.” Bioconjug Chem. 19(8): 1684-8 (2008). 22(25):5530-9 (1994). Green et al., “Quantitative evaluation of the lengths of Nishimura et al., “An efficient chemical method for removing homobifunctional protein cross-linking reagents used as molecular N-terminal extra methionine from recombinant methionylated rulers.” Protein Sci. 10(7): 1293-304 (2001). human growth hormone.” Chem Commun. 1135-6 (1998). Supplemental Partial European Search Report for European Appli Niwa et al., “A flexizyme that selectively charges amino acids cation No. 13787738.7, mailed Mar. 8, 2016 (12 pages). activated by a water-friendly leaving group.” Bioorg Med Chem Lett. 19(14):3892-4 (2009). * cited by examiner US 9,545,449 B2 1. 2 SITE-SPECIFIC LABELING AND TARGETED SUMMARY OF THE INVENTION DELIVERY OF PROTEINS FOR THE TREATMENT OF CANCER In a first aspect, the invention features a pharmaceutical composition including a therapeutic protein having a struc CROSS-REFERENCE TO RELATED ture according to formula (I), APPLICATIONS This application is a national stage of International Patent (I) Application No. PCT/US2013/040823, which claims benefit 10 P --L-T), of U.S. Provisional Application No. 61/688,308, filed May 11, 2012, 61/741,984, filed Aug. 1, 2012, 61/848,601, filed Jan. 7, 2013, and 61/849,034, filed Jan. 17, 2013, each of where which is hereby incorporated by reference in its entirety. Prepresents a monomeric protein or a multimeric protein, where P includes 1, 2, 3, or 4 proteins independently selected 15 FIELD OF THE INVENTION from cell-targeting proteins, cell-binding proteins, cell-traf ficking proteins, and transport proteins, or any combination The present invention relates to the formation of protein thereof; conjugates from proteins chemically modified for linkage to each L independently represents an organic linker group; (1) anticancer drug pharmacophores, (2) ligands to biomark each T independently represents a therapeutic agent, a ers on cancer cell Surfaces, and/or (3) another protein protein, or a ligand to a biomarkers; molecule. It provides and specifies new compositions, meth n is an integer from 0-10; and ods and combinations for tumor, and tumor vasculature where each L-T moiety present is site-specifically targeting and cancer treatment. The present invention also attached to an amino acid residue of P. and specifies fusion proteins that are produced recombinantly 25 where the compound according to formula (I) represents that can be utilized to link anticancer drug pharmacophores at least about 75% of biologically active proteins present in or ligands to biomarkers on cancer cell Surfaces, or as the composition. therapeutics in their own right because of their increased In some embodiments, n is an integer from 1-10. duration of action and T-cell mediated antitumor immunity.
Load more

Recommended publications
  • Hodgkin Lymphoma Treatment Regimens
    HODGKIN LYMPHOMA TREATMENT REGIMENS (Part 1 of 5) Clinical Trials: The National Comprehensive Cancer Network 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 health care 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 provided only to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® 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 way. Classical Hodgkin Lymphoma1 Note: All recommendations are Category 2A unless otherwise indicated. Primary Treatment Stage IA, IIA Favorable (No Bulky Disease, <3 Sites of Disease, ESR <50, and No E-lesions) REGIMEN DOSING Doxorubicin + Bleomycin + Days 1 and 15: Doxorubicin 25mg/m2 IV push + bleomycin 10units/m2 IV push + Vinblastine + Dacarbazine vinblastine 6mg/m2 IV over 5–10 minutes + dacarbazine 375mg/m2 IV over (ABVD) (Category 1)2-5 60 minutes.
    [Show full text]
  • Vincristine (Conventional): Drug Information
    Official reprint from UpToDate® www.uptodate.com ©2017 UpToDate® Vincristine (conventional): Drug information Copyright 1978-2017 Lexicomp, Inc. All rights reserved. (For additional information see "Vincristine (conventional): Patient drug information" and see "Vincristine (conventional): Pediatric drug information") For abbreviations and symbols that may be used in Lexicomp (show table) Special Alerts Vincristine Sulfate Safety Alert October 2015 Health Canada is notifying health care providers that certain lots of Hospira’s vincristine sulfate 1 mg/mL injection (DIN 02183013: 2 mL vial, list #7077A001; 5 mL vial, list #7082A001) have incorrect or outdated safety information on the inner/outer labels and package insert, which may increase the risk to patients and may result in significant patient harm requiring medical intervention. These warnings include: - Vincristine should only be administered by the intravenous (IV) route. Administration of vincristine by any other route can be fatal. - Syringes containing this product should be labeled “Warning - for IV use only.” - Extemporaneously prepared syringes containing this product must be packaged in an overwrap which is labeled “Do not remove covering until moment of injection. For IV use only - fatal if given by other routes.” - Contraindication of vincristine in patients with demyelinating Charcot-Marie-Tooth syndrome. - Potential risk of acute shortness of breath when vincristine is coadministered with mitomycin-C and GI toxicities including necrosis with administration of vincristine. Health care providers are requested to consult with the approved Canadian product monograph for vincristine sulfate 1 mg/mL for the most updated information. Consumers with questions should contact their health care provider for more information. ALERT: US Boxed Warning Experienced physician: Vincristine should be administered by individuals experienced in the administration of the drug.
    [Show full text]
  • HODGKIN LYMPHOMA TREATMENT REGIMENS (Part 1 of 2)
    HODGKIN LYMPHOMA TREATMENT REGIMENS (Part 1 of 2) The selection, dosing, and administration of anticancer agents and the management of associated toxicities are complex. Drug dose modifications and schedule and initiation of supportive care interventions are often necessary because of expected toxicities and because of individual patient variability, prior treatment, and comorbidities. Thus, the optimal delivery of anticancer agents requires a healthcare delivery team experienced in the use of such agents and the management of associated toxicities in patients with cancer. The cancer treatment regimens below may include both FDA-approved and unapproved uses/regimens and are provided as references only to the latest treatment strategies. Clinicians must choose and verify treatment options based on the individual patient. NOTE: GREY SHADED BOXES CONTAIN UPDATED REGIMENS. REGIMEN DOSING Classical Hodgkin Lymphoma—First-Line Treatment General treatment note: Routine use of growth factors is not recommended. Leukopenia is not a factor for treatment delay or dose reduction (except for escalated BEACOPP).1 CR=complete response IPS=International Prognostic Score PD=progressive disease PFTs=pulmonary function tests PR=partial response RT=radiation therapy SD=stable disease Stage IA, IIA Favorable ABVD (doxorubicin [Adriamycin] Days 1 and 15: Doxorubicin 25mg/m2 IV + bleomycin 10mg/m2 IV + vinblastine + bleomycin + vinblastine + 6mg/m2 IV + dacarbazine 375mg/m2 IV. dacarbazine [DTIC-Dome]) + Repeat cycle every 4 weeks for 2–4 cycles. involved-field radiotherapy (IFRT)1–4 Follow with IFRT after completion of chemotherapy. Abbreviated Stanford V Weeks 1, 3, 5 and 7: Vinblastine 6mg/m2 IV + doxorubicin 25mg/m2 IV. (doxorubicin + vinblastine + Weeks 1 and 5: Mechlorethamine 6mg/m2.
    [Show full text]
  • Highlights from the Pan Pacific Lymphoma Conference
    October 2011 A SPECIAL MEETING REVIEW EDITION Volume 9, Issue 10, Supplement 24 Highlights From the Pan Pacific Lymphoma Conference August 15–19, 2011 Kauai, Hawaii Special Reporting on: • Aggressive T-Cell Lymphomas • Novel Agents With Activity in CLL/SLL • PTCL—Update on Novel Therapies • Agents Targeting the Stromal Elements of the Lymph Node • Inducing Apoptosis in Lymphoma Cells Through Novel Agents With Expert Commentary by: Bruce D. Cheson, MD Deputy Chief Division of Hematology-Oncology Head of Hematology Lombardi Comprehensive Cancer Center Georgetown University Hospital Washington, DC Eb: E W Th O N www.clinicaladvances.com ENGINEERING T H E N E X T GENERATION OF ANTIBODY-DRUG CONJUGATES 003203_sgncor_adcadvcaho_fa4.indd 2 8/25/11 11:13 AM An innovative approach to improving outcomes in patients with cancer Antibody-drug conjugates (ADCs) use a conditionally stable linker to combine the targeting specificity of monoclonal antibodies with the tumor-killing power of potent cytotoxic agents.1,2 This could allow potent drugs to be delivered directly to tumor cells with minimal systemic toxicity. Optimizing the parameters for clinical success Scientists at Seattle Genetics are focused on parameters critical to the effective performance of ADCs, including target antigen selection,3,4 linker stability5-7 and potent cytotoxic agents.4,7,8 Elements of an antibody-drug conjugate Linker ADCs link precision and Antibody attaches the cytotoxic agent to specific for a tumor-associated the antibody. Newer linker potency for greater activity
    [Show full text]
  • Frontline Paid New York, Ny a Lymphoma Rounds Publication Permit #370
    Lymphoma Rounds Leadership Chicago - Loyola University Chicago New England - Baystate Medical MD, PhD; Francesca Montanari, Anna Niewiarowska, MD - Scott Smith, MD, PhD, FACP; Center - Armen Asik, MD; Beth MD; Hackensack University Medical Patrick Stiff, MD; Northwestern Israel Deaconess Medical Center Center - Andre Goy, MD, MS; Icahn Seattle - Kaiser Permanente University - Leo Gordon, MD, - Jon Arnason, MD; Robin Joyce, School of Medicine at Mount Sinai - Washington - Eric Chen, MD, PhD; FACP; Reem Karmali, MD, MS MD; Boston University School of Joshua Brody, MD; Memorial Sloan The Polyclinic - Sherry Hu, MD, (chair); Jane Winter, MD; Rush Medicine - J. Mark Sloan, MD; Kettering Cancer Center - Anthony PhD; Swedish Medical Center - University Medical Center - Jerome Brown University School of Medicine Mato, MD, MSCE; David Straus, Hank Kaplan, MD; John Pagel, Loew, MD; Sunita Nathan, MD; - Adam Olszewski, MD; Dana- MD (chair); NYU Langone Medical MD, PhD, DSc (chair); University of Parameswaran Venugopal, MD; Farber Cancer Institute - Jorge Center - Catherine Diefenbach, Washington - Paul S. Martin, MD; The University of Chicago - Sonali Castillo, MD; Ann LaCasce, MD, MD; Rutgers Cancer Institute of The University of Washington/Fred Smith, MD; Girish Venkataraman, MSc; Dartmouth-Hitchcock Medical New Jersey - Joseph Bertino, MD; Hutchinson Cancer Research Center MD; University of Illinois at Chicago Center - Elizabeth Bengtson, Andrew Evens, DO, MSc, FACP; - Stephen Smith, MD; Virginia - Frederick Behm, MD; David MD; Erick Lansigan, MD; Lahey Weill Cornell Medicine - Koen van Mason Medical Center - David Peace, MD Hospital and Medical Center - Tarun Besien, MD, PhD; Ethel Cesarman, Aboulafia, MD Kewalramani, MD; Massachusetts MD, PhD; Amy Chadburn, MD; Los Angeles - Cedars-Sinai Medical General Hospital Cancer Center- Morton Coleman, MD Washington, D.C.
    [Show full text]
  • Adcetris, INN-Brentuximab Vedotin
    19 July 2012 EMA/702390/2012 Committee for Medicinal Products for Human Use (CHMP) Assessment report Adcetris International non-proprietary name: brentuximab vedotin Procedure No. EMEA/H/C/002455 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7523 7455 E -mail [email protected] Website www.ema.europa.eu An agency of the European Union Product information Name of the medicinal product: Adcetris Applicant: Takeda Global Research and Development Centre (Europe) Ltd. 61 Aldwych London WC2B 4AE United Kingdom Active substance: brentuximab vedotin International Nonproprietary Name/Common Name: brentuximab vedotin Pharmaco-therapeutic group Monoclonal antibodies (ATC Code): (L01XC12) ADCETRIS is indicated for the treatment of adult Therapeutic indication(s): patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL): 1. following autologous stem cell transplant (ASCT) or 2. following at least two prior therapies when ASCT or multi-agent chemotherpay are not a treatment option ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). Pharmaceutical form(s): Powder for concentrate for solution for infusion Strength(s): 50 mg Route(s) of administration: Intravenous use Packaging: vial (glass) Package size(s): 1 vial Adcetris CHMP assessment report Page 2/102 Rev10.11 Table of contents 1. Background information on the procedure .............................................. 9 1.1. Submission of the dossier ...................................................................................... 9 1.2. Steps taken for the assessment of the product ....................................................... 10 2. Scientific discussion .............................................................................
    [Show full text]
  • Brentuximab Vedotin: First-Line Agent for Advanced Hodgkin Lymphoma
    ANTICANCER RESEARCH 33: 3879-3886 (2013) Brentuximab Vedotin: First-line Agent for Advanced Hodgkin Lymphoma HUYNH CAO1, KENNETH YAMAMOTO1, LI-XI YANG1,2 and ROBERT WEBER1 1St. Mary’s Medical Center, San Francisco, CA, U.S.A.; 2Radiobiology Laboratory, California Pacific Medical Center Research Institute, San Francisco, CA, U.S.A. Abstract. Hodgkin lymphoma (HL) is characterized by The mortality rate of Hodgkin lymphoma (HL) has fallen malignant Reed-Sternberg cells which express CD30. rapidly in the United States in the past five decades due to Current National Comprehensive Cancer Network guidelines the development of multiagent therapies. Among adults, for patients with advanced HL (stage III/IV disease) there are about 9,060 new cases with a reported death of recommend adriamycin, bleomycin, vinblastine, and 1,190 in 2012 (1). Current standard first-line regimens dacarbazine (ABVD), or escalated bleomycin, etoposide, include adriamycin, bleomycin, vinblastine, dacarbazine adriamycin, cyclophosphamide, vincristine, procarbazine, (ABVD), bleomycin, etoposide, adriamycin, cyclo- and prednisone (BEACOPP) as first-line regimens. ABVD phosphamide, vincristine, procarbazine, prednisone appears to be as effective, with fewer side effects, as (BEACOPP) and Stanford V. Brentuximab vedotin, the first escalated BEACOPP. Escalated BEACOPP leads to a Food and Drug Administration (FDA)-approved agent for the greater progression-free survival but no difference in overall treatment of HL in over three decades, has been well-studied survival. Recent advancements in technology have enabled in many trials as a second-line agent after prior failed an exciting shift to molecular-targeted cancer therapy. chemotherapies. However, through our comprehensive Brentuximab vedotin, a CD30-directed antibody conjugate, literature research we did not find any study that reported the specifically targets malignant HL cells.
    [Show full text]
  • ABVD Versus Modified Stanford V Versus MOPPEBVCAD With
    ABVD versus modified stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate- and advanced-stage Hodgkin's lymphoma: final results of a multicenter randomized trial by the Intergruppo Italiano Linfomi. Gobbi PG, Levis A, Chisesi T, Broglia C, Vitolo U, Stelitano C, Pavone V , Cavanna L, Santini G , Merli F , Liberati M ,Baldini L , Deliliers GL, Angelucci E, Bordonaro R , Federico M ;Intergruppo Italiano Linfomi . PURPOSE: In this multicenter, prospective, randomized clinical trial on advanced Hodgkin's lymphoma (HL), the efficacy and toxicity of two chemotherapy regimens, doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) and mechlorethamine, vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine (MOPPEBVCAD), were compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as standard therapy to select which regimen would best support a reduced radiotherapy program, which was limited to < or = two sites of either previous bulky or partially remitting disease (a modification of the original Stanford program). PATIENTS AND METHODS: Three hundred fifty-five patients with stage IIB, III, or IV HL were randomly assigned. Three hundred thirty-four patients were assessable for the study and received six cycles of ABVD (n = 122), three cycles of Stanford V (n = 107), or six cycles of MOPPEBVCAD (n = 106); radiotherapy was administered to 76, 71, and 50 patients in these three arms, respectively. RESULTS: The complete response rates for ABVD, Stanford V, and MOPPEBVCAD were 89%, 76% and 94%, respectively; 5-year failure-free survival (FFS) and progression-free survival rates were 78%, 54%, 81% and 85%, 73%, and 94%, respectively (P < .01 for comparison of Stanford V with the other two regimens).
    [Show full text]
  • Appendix C Medication Tables
    Appendix C Medication Tables Note: The medication tables are not meant to be inclusive lists of all available therapeutic agents. Approved medication tables will be updated regularly. Discrepancies must be reported. See Resource Section of this manual for additional contact information. Release Notes: Aspirin Table Version 1.0 Table 1.1 Aspirin and Aspirin-Containing Medications Acetylsalicylic Acid Acuprin 81 Alka-Seltzer Alka-Seltzer Morning Relief Anacin Arthritis Foundation Aspirin Arthritis Pain Ascriptin Arthritis Pain Formula ASA ASA Baby ASA Baby Chewable ASA Baby Coated ASA Bayer ASA Bayer Children's ASA Buffered ASA Children's ASA EC ASA Enteric Coated ASA/Maalox Ascriptin Aspergum Aspir-10 Aspir-Low Aspir-Lox Aspir-Mox Aspir-Trin Aspirbuf Aspircaf Aspirin Aspirin Baby Aspirin Bayer Aspirin Bayer Children's Aspirin Buffered Aspirin Child Aspirin Child Chewable Aspirin Children's Aspirin EC Aspirin Enteric Coated Specifications Manual for National Appendix C-1 Hospital Quality Measures Table 1.1 Aspirin and Aspirin-Containing Medications (continued) Aspirin Litecoat Aspirin Lo-Dose Aspirin Low Strength Aspirin Tri-Buffered Aspirin, Extended Release Aspirin/butalbital/caffeine Aspirin/caffeine Aspirin/pravachol Aspirin/pravastatin Aspirtab Bayer Aspirin Bayer Aspirin PM Extra Strength Bayer Children’s Bayer EC Bayer Enteric Coated Bayer Low Strength Bayer Plus Buffered ASA Buffered Aspirin Buffered Baby ASA Bufferin Bufferin Arthritis Strength Bufferin Extra Strength Buffex Cama Arthritis Reliever Child’s Aspirin Coated Aspirin
    [Show full text]
  • Order Set: Stanford V Mechlorethamine 6 Mg/M2
    (Place Patient Identification Sticker Here) attach patient label here Physician Orders ADULT Order Set: Stanford V Diagnosis : Hodgkins Lymphoma Height: cm Weight: kg Cycle: Of : Actual BSA: m2 Treatment BSA: m2 Day/Wk: Freq: Allergies: [ ] No known allergies [ ]Medication allergy(s): [ ] Latex allergy [ ]Other: Vital Signs [ ] Vital Signs T;N, q15 min for 1 hour, Comment: once bleomycin test dose has been administered Patient Care [ ] Nursing Communication T;N, Do not exceed a treatment BSA of m2 [ ] Nursing Communication T;N, May hold hydration during chemotherapy infusion [ ] Nursing Communication T;N, Verify patient has had MUGA or ECHO to r/o Cardiac dysfunction prior to chemotherapy Continuous Infusions Pre Hydration [ ] Normal Saline 1,000 mL, IV, Routine, mL/hr , ??? How much Medications Pre Medications NOTE: Administer the below TEST DOSE before the first dose of bleomycin [X] bleomycin 2 units, IV, IV Push, TEST DOSE , Wait a minimum of 1 hour before administering the remainder of dose CHEMOTHERAPY Drug (generic) & solution Intended Dose Actual Dose Route, Infusion, Frequency and total (optional) doses [X] 2 IV Push, Once on DAY 1 mechlorethamine 6 mg/m [X] 2 IV Push, Once on DAY 1 and DAY 15 DOXOrubicin 25 mg/m [X] 2 IV Push, Once on DAY 1 and DAY 15 vinBLAstine 6 mg/m [X] 2 IV Push, Once on DAY 8 and DAY 22, vinCRIStine 1.4 mg/m MAX DOSE 2 mg [X] 2 IV Piggyback, Infuse over 60 min, Once bleomycin 5 units/m on DAY 8 and 22 [X] 2 IV Piggyback, Infuse over 60 min, Once etoposide 60 mg/m on DAY 15 and 16 [X] 2 PO, Every other
    [Show full text]
  • Clinical Research Newsletter for Colleagues in the Community
    Clinical Research Newsletter for Colleagues in the Community Welcome to the Winter 2016 issue of the target hematologic disease at is most basic origins. Stanford Cancer Institute Clinical Research The Stanford Hematology Program offers state-of-the- Newsletter for Colleagues in the Community. art diagnostics, clinical trials and treatment regimens for This quarterly publication is designed patients with a variety of hematologic disorders. Clinical to inform our colleagues in the medical community, and trial offerings include early stage trials of novel agents to especially physicians who are considering treatment options late stage randomized trials comparing different therapies. for their patients with cancer, about current clinical trials Hematologists work closely with specialists in BMT, infectious available at the NCI-designated Stanford Cancer Institute. diseases, radiation oncology, and interventional radiology. Many of these trials provide access to novel therapies including This program is committed to improving outcomes and new “targeted” agents, often not available in the community. quality of life through contributions to the prestigious National As the director of the Lymphoma program, I am pleased to Comprehensive Cancer Network (NCCN) guidelines. introduce this issue presenting Stanford’s BMT, Hematology, The Stanford Lymphoma Program offers multidisciplinary, and Lymphoma programs. Each of these programs is personalized diagnostics and treatment for patients with Non- nationally recognized for improving patient outcomes by Hodgkin’s Lymphoma (NHL) and Hodgkin’s Disease. For over 50 translating clinical research into new treatments. years Stanford researchers and clinicians have helped define This issue also introduces our brand new Adolescent & Young the standard of care for lymphomas, pioneering breakthrough Adult (AYA) cancer program, designed to meet the unique immunotherapies, and monoclonal antibodies.
    [Show full text]
  • Hodgkin Lymphoma—Stage III and IV
    Date of origin: 1999 Last review date: 2016 American College of Radiology ACR Appropriateness Criteria® HODGKIN LYMPHOMA — STAGE III AND IV Expert Panel on Radiation Oncology–Hodgkin Lymphoma: John P. Plastaras, MD, PhD1; Ranjana Advani, MD2; Leslie K. Ballas, MD3; Bouthaina S. Dabaja, MD4; Sughosh Dhakal, MD5; Christopher R. Flowers, MD, MS6; Chul S. Ha, MD7; Bradford S. Hoppe, MD, MPH8; David B. Mansur, MD9; Nancy P. Mendenhall, MD10; Monika L. Metzger, MD11; Kenneth B. Roberts, MD12; Ronald Shapiro, MD13; Sonali M. Smith, MD14; Stephanie A. Terezakis, MD15; Karen M. Winkfield, MD, PhD16; Anas Younes, MD17; Louis S. Constine, MD.18 Summary of Literature Review Introduction/Background This review for Hodgkin lymphoma (HL) addresses the treatment of patients who are newly diagnosed with clinical stage III or IV HL. There is only low-level evidence on the treatment of stage III or IV nodular lymphocyte-predominant HL, so this review is limited to advanced-stage classical Hodgkin lymphoma (cHL). It is the result of a comprehensive review of the literature and expert opinion. A combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) has been the most widely used chemotherapy regimen for HL. Alternatives to ABVD have been developed for patients with locally extensive or advanced-stage disease, including BEACOPP (a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and its variants and the Stanford V regimen. Dose-escalated BEACOPP and its variants have been shown to be superior to standard-dose chemotherapy, although at the expense of increased toxicity, including infertility and leukemia risks. Stanford V, when given with radiation therapy (RT) as specified by the original protocol (involved-field RT [IFRT] to initial sites ≥5 cm and/or macroscopic splenic disease), yields results comparable to those of ABVD.
    [Show full text]