Eliminating Vincristine Administration Events
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Modifications on the Basic Skeletons of Vinblastine and Vincristine
Molecules 2012, 17, 5893-5914; doi:10.3390/molecules17055893 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Modifications on the Basic Skeletons of Vinblastine and Vincristine Péter Keglevich, László Hazai, György Kalaus and Csaba Szántay * Department of Organic Chemistry and Technology, University of Technology and Economics, H-1111 Budapest, Szt. Gellért tér 4, Hungary * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel: +36-1-463-1195; Fax: +36-1-463-3297. Received: 30 March 2012; in revised form: 9 May 2012 / Accepted: 10 May 2012 / Published: 18 May 2012 Abstract: The synthetic investigation of biologically active natural compounds serves two main purposes: (i) the total synthesis of alkaloids and their analogues; (ii) modification of the structures for producing more selective, more effective, or less toxic derivatives. In the chemistry of dimeric Vinca alkaloids enormous efforts have been directed towards synthesizing new derivatives of the antitumor agents vinblastine and vincristine so as to obtain novel compounds with improved therapeutic properties. Keywords: antitumor therapy; vinblastine; vincristine; derivatives 1. Introduction Vinblastine (1) and vincristine (2) are dimeric alkaloids (Figure 1) isolated from the Madagaskar periwinkle plant (Catharantus roseus), exhibit significant cytotoxic activity and are used in the antitumor therapy as antineoplastic agents. In the course of cell proliferation they act as inhibitors during the metaphase of the cell cycle and by binding to the microtubules inhibit the development of the mitotic spindle. In tumor cells these agents inhibit the DNA repair and the RNA synthesis mechanisms, blocking the DNA-dependent RNA polymerase. Molecules 2012, 17 5894 Figure 1. -
National Dose Banding Table – Single Container
National Dose Banding Table – Single Container Arsenic Trioxide Cisplatin Cladribine (Leustat) Strength of raw material 1 mg/mL Example drug(s) Idarubicin (after reconstitution if required) Mitomycin Vinblastine Vincristine See table usage notes below regarding ‘single container’ and ‘multiple syringe’ tables. Master Bands and Ranges This table is intended to be in a format useful for electronic prescribing systems. Use To (A) if your system will round UP for doses on the step between two bands. Use To (B) if your system will round DOWN for doses on the step between two bands. Band Range (mg) Band Dose Variance (percent) From ≥ To (A) < To (B) ≤ (mg) Below Above 0.21 0.23 0.22 0.22 5 -4 0.23 0.25 0.24 0.24 4 -4 0.25 0.27 0.26 0.26 4 -4 0.27 0.29 0.28 0.28 4 -3 0.29 0.32 0.31 0.3 3 -6 0.32 0.36 0.35 0.34 7 -5 0.36 0.40 0.39 0.38 6 -5 0.40 0.44 0.43 0.42 5 -5 0.44 0.49 0.48 0.46 5 -6 0.49 0.55 0.54 0.52 6 -5 0.55 0.61 0.60 0.58 6 -5 0.61 0.68 0.67 0.64 5 -6 0.68 0.76 0.75 0.72 6 -5 0.76 0.85 0.84 0.8 5 -6 0.85 0.95 0.94 0.9 6 -5 0.95 1.05 1.04 1 5 -5 1.05 1.15 1.14 1.1 5 -4 1.15 1.25 1.24 1.2 4 -4 1.25 1.35 1.34 1.3 4 -4 1.35 1.45 1.44 1.4 4 -3 1.45 1.55 1.54 1.5 4 -3 1.55 1.65 1.64 1.6 3 -3 1.65 1.75 1.74 1.7 3 -3 1.75 1.90 1.89 1.8 3 -5 1.90 2.10 2.09 2 5 -5 2.10 2.30 2.29 2.2 5 -4 2.30 2.50 2.49 2.4 4 -4 2.50 2.70 2.69 2.6 4 -4 2.70 2.90 2.89 2.8 4 -3 2.90 3.10 3.09 3 4 -3 3.10 3.30 3.29 3.2 3 -3 3.30 3.50 3.49 3.4 3 -3 3.50 3.80 3.79 3.6 3 -5 3.80 4.20 4.19 4 5 -5 4.20 4.60 4.59 4.4 5 -4 Chemotherapy Dose Standardisation Band Range (mg) -
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. -
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. -
Effect of Human Fibroblast Interferon on the Antiviral Activity of Mammalian Cells Treated with Bleomycin, Vincristine, Or Mitomycin C1
[CANCER RESEARCH 43, 5462-5466. November 1983] Effect of Human Fibroblast Interferon on the Antiviral Activity of Mammalian Cells Treated with Bleomycin, Vincristine, or Mitomycin C1 Robert J. Suhadolnik,2 Yosuke Sawada,3 Maryann B. Flick, Nancy L. Reichenbach, and Joseph D. Mosca3 Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140 ABSTRACT protein kinase (2,9,28,34,36). In addition to the use of interferon in the treatment of cancer (1, 11, 12, 29, 34), combination Bleomycin, vincristine, or mitomycin C, when added to HeLa chemotherapy of interferon and methotrexate, c/s-platinum diam- cells simultaneously with human fibroblast interferon (IFN-0), minedichloride, cyclophosphamide, or 1,3-bis(/i-chloroethyl)-1- caused a decrease in cell density and inhibited DMA synthesis nitrosourea on either tumor cells in culture or in leukemic mice compared with HeLa cells treated with IFN-/3 alone. However, has been reported (5, 7, 10, 25). Furthermore, Stolfi ef al. (37) the IFN-0-induced antiviral processes were unaffected by the reported recently that the administration of mouse interferon to presence of these drugs as determined by in vitro enzyme assays mice following the administration of 5-fluorouracil protected the and the development of the antiviral state in the intact HeLa cell. mice from mortality. Because it is possible to selectively inhibit HeLa cells treated with IFN-/Õalone or with IFN-/3 in combination proliferation of tumor cells with chemotherapeutic drugs, we with bleomycin, vincristine, or mitomycin C were able to induce reasoned that the ability of the normal cell to maintain the antiviral the double-stranded RNA-dependent adenosine triphos- phate:2',5'-oligoadenylic acid adenyltransferase (EC 2.2.2.-) and state might be adversely affected by such drugs and that the antiproliferative action of interferons might affect the activity of the double-stranded RNA-dependent protein kinase. -
BC Cancer Benefit Drug List September 2021
Page 1 of 65 BC Cancer Benefit Drug List September 2021 DEFINITIONS Class I Reimbursed for active cancer or approved treatment or approved indication only. Reimbursed for approved indications only. Completion of the BC Cancer Compassionate Access Program Application (formerly Undesignated Indication Form) is necessary to Restricted Funding (R) provide the appropriate clinical information for each patient. NOTES 1. BC Cancer will reimburse, to the Communities Oncology Network hospital pharmacy, the actual acquisition cost of a Benefit Drug, up to the maximum price as determined by BC Cancer, based on the current brand and contract price. Please contact the OSCAR Hotline at 1-888-355-0355 if more information is required. 2. Not Otherwise Specified (NOS) code only applicable to Class I drugs where indicated. 3. Intrahepatic use of chemotherapy drugs is not reimbursable unless specified. 4. For queries regarding other indications not specified, please contact the BC Cancer Compassionate Access Program Office at 604.877.6000 x 6277 or [email protected] DOSAGE TUMOUR PROTOCOL DRUG APPROVED INDICATIONS CLASS NOTES FORM SITE CODES Therapy for Metastatic Castration-Sensitive Prostate Cancer using abiraterone tablet Genitourinary UGUMCSPABI* R Abiraterone and Prednisone Palliative Therapy for Metastatic Castration Resistant Prostate Cancer abiraterone tablet Genitourinary UGUPABI R Using Abiraterone and prednisone acitretin capsule Lymphoma reversal of early dysplastic and neoplastic stem changes LYNOS I first-line treatment of epidermal -
Transitional Cell Carcinoma: Options Beyond Nsaids Julie Marie Gillem, DVM, DACVIM (Oncology) Overview
Transitional Cell Carcinoma: Options Beyond NSAIDs Julie Marie Gillem, DVM, DACVIM (Oncology) Overview ✦ Background ✦ Surgical Options ✦ Pathology ✦ Medical Options ✦ Location and staging ✦ Radiation Therapy ✦ Behavior Options ✦ Etiology and risk factors ✦ Palliative care ✦ Work up and diagnosis ✦ What about cats? Objectives ✦ How do we determine when NSAIDs fail? ✦ When should we intervene with surgery, chemotherapy, radiation therapy, and additional palliative care? Pathology ✦ ~2% of canine cancer ✦ Invasive transitional cell carcinoma (TCC) most common ✦ Others: SCC, adenocarcinoma, undifferentiated carcinoma, rhabdomyosarcoma, fibroma, and other mesenchymal tumors Location and Staging ✦ TCC in dogs most often found in the trigone of the bladder ✦ Series of 102 dogs at PUVTH ✦ Urethra and bladder in 56% ✦ Prostate involvement in 29% male dogs ✦ Lymph node mets in 16% at diagnosis ✦ Distant mets in 14% at diagnosis ✦ Distant mets in 50% at death Location ✦ TCC in dogs most often is found in the trigone region of the bladder. ✦ In a series of dogs with TCC examined at the PUVTH, the tumor involved the urethra as well as the bladder in 57 of 102 dogs (56%), and it involved the prostate in 11 of 38 (29%) male dogs. WHO Staging ✦ 78% T2 tumors ✦ 20% T3 tumors Biological Behavior ✦ At diagnosis: ✦ Regional lymph node metastasis in 12-46 % (Norris et al 1992, Knapp et al 2000, Blackburn et al 2013) ✦ Distant metastasis in 16- 23% (Norris et al 1992, Blackburn et al 2013) ✦ Distant metastasis in 50% at death (Norris et al 1992, Knapp et al -
Vincristine Archive File
Vincristine archive file Vincristine is a vinakaloid, which was first discovered 1958 in the tropical plant Catharanthus roseus, native in Madagascar. Its ability to inhibit the metaphase of the mitosis by suppressing the polymerization of the microtubule makes it very important as a chemotherapeutic agent, especially against non-Hodgkin lymphomas and Wilms' tumor. History: Vinblastine and Vincristine are bisindole alkaloids and both widely known for their use as antitumor drugs. In former times they were isolated in trace quantities from the leaves of Catharanthus roseus. Because of their importance in the medical field numerous researches were examining the structure, use and synthesis of Vinblastine, Vincristine and their derivates. Their biological effect to inhibit the microtubule formation and mitosis was and still is a very important part of medical cancer therapy. They were both among the first natural products whose structures were identified by X-ray crystallography and among the first for which X-ray analysis of a heavy atom derivative was used to establish their absolute configuration. ( 2) Timeline: 1958 Vinblastine was first discovered as an unexpected myelosuppressive agent by Noble, R. L., C. T. Beer, and J. H. Cutts during the search for an antidiabetic agent in Catharanthus roseus (myelosupression decreased activity of the bone marrow) 1959 independendently researchers from Eli Lilly (Johnson, I. S., J. G. Armstrong, M. Gorman, and J. P. Burnett, Jr.)discovered that the extracts of C. roseus Possesses activity against -
Paclitaxel, Vinorelbine and 5-Fluorouracil in Breast Cancer Patients Pretreated with Adjuvant Anthracyclines
British Journal of Cancer (2005) 92, 634 – 638 & 2005 Cancer Research UK All rights reserved 0007 – 0920/05 $30.00 www.bjcancer.com Paclitaxel, vinorelbine and 5-fluorouracil in breast cancer patients pretreated with adjuvant anthracyclines Clinical Studies 1 1 1 2 2 2 3 3 A Berruti , R Bitossi , G Gorzegno , A Bottini , D Generali , M Milani , D Katsaros , IA Rigault de la Longrais , 3 4 4 4 5 6 6 7 R Bellino , M Donadio , M Ardine , O Bertetto , S Danese , MG Sarobba , A Farris , V Lorusso and ,1 L Dogliotti* 1Oncologia Medica, Azienda Ospedaliera San Luigi, Regione Gonzole 10, 10043 Orbassano (TO), Italy; 2Breast Unit, Azienda Ospedaliera Istituti Ospitalieri, largo Priori, 26100 Cremona, Italy; 3Ginecologia Oncologica, Azienda Ospedaliera OIRM Sant’Anna, via Ventimiglia 3, 10126 Torino, Italy; 4 Oncologia Medica, Centro Oncologico Ematologico Subalpino, Azienda Ospedaliera San Giovanni Battista Molinette, corso Bramante 88, 10126 Torino, 5 6 Italy; Ginecologia Divisione A, Azienda Ospedaliera OIRM Sant’Anna, corso Spezia 60, 10126 Torino, Italy; Oncologia Medica, Istituto Clinica Medica 7 Universitaria, via San Pietro 8, 07100 Sassari, Italy; Oncologia Medica, Istituto Oncologico, via Amendola 209, 70126 Bari, Italy We investigated the activity and toxicity of a combination of vinorelbine (VNB), paclitaxel (PTX) and 5-fluorouracil (5-FU) continuous infusion administered as first-line chemotherapy in metastatic breast cancer patients pretreated with adjuvant À2 À2 anthracyclines. A total of 61 patients received a regimen consisting of VNB 25 mg m on days 1 and 15, PTX 60 mg m on days 1, 8 À2 and 15 and continuous infusion of 5-FU at 200 mg m every day. -
Differential Activity of Vincristine and Vinblastine Against Cultured Cells1 ;
[CANCER RESEARCH 44, 3307-3312, August 1984] Differential Activity of Vincristine and Vinblastine against Cultured Cells1 ; Peter J. Ferguson,2 J. Robert Phillips, Milada Seiner, and Carol E. Cass3 Cancer Research Group (McEachern Laboratory) [P. J. F., J. Ft. P., M. S., C. E. C.] and Department of Biochemistry [P. J. F., C. E. C.¡,University of Alberta, Edmonton, Alberta, Canada T6G 2H7 ABSTRACT determine if differential activity is related to differences in uptake4 or release of drug. Included were cells from these established Vincristine and vinblastine exhibit differential activity against lines: mouse neuroblastoma; mouse leukemia L1210; mouse tumors and normal tissues. In this work, a number of cultured lymphoma S49; HeLa; and human promyelocytic leukemia HL- cell lines were assayed for their sensitivity to the antiproliferative 60. Drug sensitivity in each cell line was determined by assaying and cytotoxic effects of the two drugs following short-term (4 hr) inhibition of proliferation during a continuous exposure to either or during continuous exposures. Differential activity was not drug or by assaying colony formation following a 24-hr exposure. seen when cells were subjected to continuous exposures. The Because of rapid loss of Vinca alkaloids from human serum concentrations of Vincristine and vinblastine, respectively, that following an i.v. bolus injection (11, 12,14, 17), the sensitivity of inhibited growth rates by 50% were: mouse leukemia L1210 cells to short-term (1- and 4-hr) exposures was also determined cells, 4.4 and 4.0 nw; mouse lymphoma S49 cells, 5 and 3.5 nM; for both drugs. Although there were differences in sensitivity to mouse neuroblastoma cells, 33 and 15 nw; HeLa cells, 1.4 and vincristine and vinblastine between cell lines, there was little or 2.6 nw; and human leukemia HL-60 cells, 4.1 and 5.3 nM. -
Etoposide Compared with the Combination of Vincristine, Doxorubicin, and Cyclophosphamide in the Treatment of Small Cell Lung Cancer
Thorax 1989;44:215-219 Thorax: first published as 10.1136/thx.44.3.215 on 1 March 1989. Downloaded from Etoposide compared with the combination of vincristine, doxorubicin, and cyclophosphamide in the treatment of small cell lung cancer M B McILLMURRAY, R J BIBBY, BE TAYLOR, L P ORMEROD, J R EDGE, R J WOLSTENHOLME, R F WILLEY, J F O'REILLY, N HORSFIELD, C E JOHNSON, C P MUSTCHIN, D BRISCOE From the Royal Lancaster Infirmary, Lancaster; Victoria Hospital, Blackpool; Royal Preston Hospital, Preston; Blackburn Royal Infirmary, Blackburn; Marsden Hospital, Burnley; Furness General Hospital, Cumbria; Cumberland Infirmary, Carlisle; and Royal Albert Edward Infirmary, Wigan ABSTRACT One hundred and three patients with small cell lung carcinoma were stratified according to stage ofdisese (47 limited disease, 56 extensive disease) and then randomised to receive etoposide 300 mg/m2 alone for two days or a combination (VAC) of vincristine 1 mg/m2, doxorubicin (Adriamycin) 50 mg/m2, and cyclophosphamide 1000 mg/m2. The drugs were given at three week intervals. Patients were assessed after three cycles of treatment and continued with the same regimen ifin complete remission and with the alternative regimen ifin partial remission; they were withdrawn if the disease had progressed. Twenty four patients (23%) achieved complete remission and this copyright. occurred more often when patients were receiving VAC (19 of82) than etoposide (5 of75). There was no difference, however, in overall survival between those initially treated with etoposide and those having combination chemotherapy, whether for limited disease (both 8 months) or extensive disease (7 and 5 5 months). -
Natural Products. a History of Success and Continuing Promise for Drug Discovery and Development
Natural Products. A History of Success and Continuing Promise for Drug Discovery and Development Gordon M. Cragg NIH Special Volunteer [email protected] David J. Newman Natural Products Branch Developmental Therapeutics Program National Cancer Institute EARLY DOCUMENTATION OF USE OF MEDICINAL PLANTS http://www.nlm.nih.gov/hmd/collections/archives/index.html • Mesopotamian ~2,600 B. C. E. • Egyptian ~ 1,800 B. C. E. • Chinese – ~1,100 B. C. E. and continuing • Indian ~ 1,000 B. C. E. and continuing • Greek ~ 500 B. C. E. Greco-Roman expertise preserved and coordinated with other traditions by Islamic cultures during the Dark Ages ~ 400-1,100 CE Avicenna. Persian pharmacist, physician, poet, philosopher author: canon medicinae – “final codification of Greco-Roman medicine” Great Moments in Pharmacy Collection APhA Traditional Medicine and Drug Discovery • 80% of the world population resides in developing countries • 80% of people in developing countries utilize plants to meet their primary health care needs • Global pop. ca. 7 billion ca. 4.5 billion people utilize plants to meet their primary health care needs Farnsworth NR, et al. Medicinal Plants in Therapy. Bull. W.H.O. 63:965-981 (1985) Fabricant and Farnsworth, EnViron. Health Perspect. 109, 69-75 (2001) Cordell and Clovard, J. Nat. Prod., 75, 514-525 (2012) Norman Farnsworth 1800s. Discovery of some active principles of major herbal preparations Newman and Cragg. Natural Product Chemistry for Drug Discovery, eds. Buss and Butler, M. S., Royal Soc. Chem., Cambridge, 2010, pp. 3-27 European chemists (apothecaries) revolutionized drug discovery and development. 1817. Sertϋrner reports isolation of morphine from Papaver somniferum.