DOCSLIB.ORG

Differential Activity of Vincristine and Vinblastine Against Cultured Cells1 ;

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
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. In no difference in sensitivity to the 2 drugs within a given cell line contrast, differential toxicity was seen when cells were subjected during continuous exposures. In contrast, after exposures of 4 to 4-hr exposures and transferred to drug-free medium: the 50% hr or less, L1210 and HL-60 cells were much more sensitive to growth-inhibitory concentrations for Vincristine and vinblastine, vincristine than to vinblastine. Experiments were undertaken to respectively, for inhibition (a) of proliferation of L1210 cells were determine if the difference in sensitivity of L1210 cells to vincris 100 and 380 nM and of HL-60 cells were 23 and 900 nM and (b) tine and vinblastine after short exposures was due to differences of colony formation of L1210 cells were 6 and >600 nM and of HeLa cells were 33 and 62 nM. Uptake and release of [3H]- in uptake and/or release of the drugs by cells. Others have vincristine and [3H]vinblastine were examined in L1210 cells observed that vinblastine associates with and is released more quickly from rat platelets than vincristine (8). Radiolabeled vin under the conditions of growth experiments. Uptake of both cristine and vinblastine were utilized in assaying uptake and drugs was dependent on the pH of culture media, and signifi release of drugs from the cells during and following 4-hr expo cantly greater amounts of [3H]vinblastine than of [3H]vincristine sures. The results obtained suggest that rapid release of vin were associated with cells after 4-hr exposures to equal concen blastine by cells is the reason for its lesser toxicity, compared trations of either drug. When cells were transferred to drug-free with vincristine, after 1- or 4-hr exposures. medium after 4-hr exposures, vinblastine was released much more rapidly from cells than was Vincristine, and by 0.5 hr after MATERIALS AND METHODS resuspension of cells, the amount of Vincristine associated with the cells was greater than the amount of vinblastine and remained Cell Culture so for up to at least 6 hr. Unless otherwise noted, stock cultures of the cell lines described below were restarted after 30 to 40 subculture generations from frozen INTRODUCTION cells that had been demonstrated to be free of Mycoplasma (Dr. J. Robertson, Medical Bacteriology, University of Alberta). Stock cultures Vincristine and vinblastine are potent mitotic inhibitors that were routinely maintainedin antibiotic-freegrowth medium of the appro have been used clinically in the treatment of a variety of neo priate type and were expanded in antibiotic-containingmedium(penicillin, plasms. Although they differ in their molecular structure by only 100 units/ml; streptomycin, 100 ¿/g/ml;and,in some cases, gentamycin, 50 Mg/ml)to obtain cells for experimental use. All cultures were grown one carbonyl group, vinblastine and Vincristine exhibit quite at 37°in5% CO2in air, and cell numbers were determined by enumer different spectra of activity in both their targets of antitumor activity and their sites of dose-limiting toxicity. The major sites ation with an electronic particle counter (Coulter Electronics, Hialeah, FL). of toxicity for Vincristine and vinblastine, respectively, are the L1210 Cells.TheoriginandcharacteristicsofmouseleukemiaL1210/ nervous system and the hematopoietic system (1). C2 cells have been described (2). Stock cultures were routinely main The objectives of the current study were to identify cell types tained in Fischer's medium with 10% horse serum, and 5 mw HEPES5 that differ in their sensitivity to Vincristine and vinblastine and to and antibiotics were added to the growth medium of experimental cultures. Cells grew exponentially with doubling times of 14 to 16 hr. ' Supported by the National Cancer Institute of Canada and the Alberta Heritage Savings Trust Fund: Applied Research—Cancer. Portions of this work were ' Uptake refers to total cell-associated drug and may include drug adsorbed to presented in a preliminary report (7). cell surfaces as well as internalized drug. 2 Recipient of a Studentship Award from the Alberta Heritage Foundation for 5 The abbreviations used are: HEPES, A/-2-hydroxyethylpiperazine-W'-2-eth- Medical Research. anesulfonate; \CM. concentration of drug that inhibited proliferation rates by 50% 3 To whom requests for reprints should be addressed. over the period of time specified in text; IQ»,concentration of drug that gave 10% Received August 22, 1983; accepted May 8, 1984. survival. AUGUST1984 3307 Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1984 American Association for Cancer Research. P. J. Ferguson et al. The effects of drugs on proliferation and viability of L1210/C2 cells after single cells was obtained, and counting with an electronic particle coun 4- or 24-hr exposures were determined as described previously (2). ter. S49 Cells. Mouse lymphoma S49 cells were provided by Dr. D. W. Martin, Jr., University of California, San Francisco, CA, and were main Uptake and Release of Wnca Alkaloids tained in the same manner as L1210 cells. Drug effects on cell prolifer Uptake of [3H]vinblastine and [3H]vincristine by L1210 cells was mea ation were also determined as described for L1210 cells (2). Cells grew exponentially with doubling times of about 15 hr. sured by a modification of a procedure described previously for use in studies of uptake of 3H-nucleosides by suspended cells (9). Solutions HL-60 Cells. Human promyelocytic leukemia HL-60 cells (6) were a containing 3H-labeled drug at twice the concentration to be tested were generous gift from Dr. R. Gallo, NIH, Bethesda, MD. Growth medium prepared in Fischer's growth medium with 10% horse serum and 5 mw consisted of Roswell Park Memorial Institute Medium 1640 supple mented with 15% fetal calf serum. Stock cultures were subcultured 3 or HEPES (pH 7.4). Uptake experiments were initiated by combining equal more times per week by diluting cells to 105/ml. Such cells grew expo volumes of logarithmically growing cells (3 x 10s cells/ml) and the 3H- drug solution and incubating at 37°.At graded time intervals, duplicate nentially with doubling times of about 36 hr. Drug effects on proliferation of HL-60 cells were determined by a modification of the procedure 1-ml samples of the reaction mixtures were transferred to 1,5-ml poly propylene microcentrifuge tubes and centrifuged 1 min in a microcentri- described previously (2) for L1210 cells. Drug exposures were initiated by combining suspensions of exponentially proliferating cells (2 x 105 fuge. The supematants were aspirated, and the cell pellets were washed cells/ml) with equal volumes of fresh growth medium containing drug at by resuspending in 1 ml of cold 0.15 M NaCI solution and centrifuging. The 3H content of cell pellets was determined by removing the superna twice the concentration to be tested. Duplicate cultures were prepared tant and solubilizing the pellet in 100 >i\of 1% Triton X-100 (v/v). Tubes for each drug concentration. For exposures of 4 hr, cells were removed from the drug solution by centrifugation, washed, and resuspended in were uncapped, placed in plastic scintillation vials, and filled with 8 ml of the original volume of drug-free growth medium. Cell recovery was about a xylene:detergent scintillant (16) for determination of radioactivity by 85 to 90% for all cultures including controls. liquid scintillation counting. In some experiments, the water content of cell pellets and the intra- and extracellular water spaces were determined HeLa Cells. Maintenance of stock cultures of HeLa S3 cells and by measuring uptake of [3H]sucrose or 3H2O as described previously (9). expansion of cells for experimental use were carried out as described previously (3). In suspension cultures, cell concentrations were main The number of cells in reaction mixtures was determined by processing tained below 5 x 105 cells/ml, and cell proliferation was exponential with additional samples at each time point as described above, except that doubling times of about 20 hr.
Load more

Recommended publications
  • 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.
    [Show full text]
  • 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)
    [Show full text]
  • 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]
  • 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.
    [Show full text]
  • 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
    [Show full text]
  • 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
    [Show full text]
  • Eliminating Vincristine Administration Events
    Issue 37 October 2017 Eliminating vincristine administration events Issue: Despite the usually deadly consequences of accidentally administering the chemotherapy drug vincristine intrathecally, adverse events still occur, typically because some organizations still administer vincristine via syringe. The good news is that these events are happening less in the United States, mostly because of the efforts of leading national organizations to promote an effective prevention strategy that assures a mechanical barrier to intrathecal administration (into the subarachnoid space). The strategy involves diluting intravenous vincristine or other vinca alkaloids in a minibag that contains a volume that is too large for intrathecal administration (e.g., 25 mL for pediatric patients and 50 mL for adults), making it mechanically difficult to accidentally administer intrathecally.1 Vinca alkaloids (vinblastine, vinorelbine, vincristine, and vincristine liposomal) are chemotherapy drugs that are intended to be administered intravenously. If given intrathecally, vincristine is nearly always fatal and associated with an irreversible, painful ascending paralysis.2 When vinca alkaloids are injected intrathecally, destruction of the central nervous system occurs, radiating out from the injection site. The few survivors of this adverse event experienced devastating neurological damage.1 Part of the problem stems from ordering intravenous vincristine in conjunction with medications that are administered intrathecally via a syringe, such as methotrexate, cytarabine and hydrocortisone. In some adverse events, vincristine was mistakenly injected into the cerebrospinal fluid (CSF) of patients when the intent was to inject another intrathecal chemotherapy agent, such as methotrexate or cytarabine.3 Intravenous vincristine and other vinca alkaloids are dispensed from the pharmacy with explicit warning labels about their lethality if given intrathecally.
    [Show full text]
  • 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
    [Show full text]
  • VINBLASTINE-VINCRISTINE (Chlvpp-EVA
    Chemotherapy Protocol LYMPHOMA CHLORAMBUCIL-DOXORUBICIN-ETOPOSIDE-PREDNISOLONE-PROCARBAZINE- VINBLASTINE-VINCRISTINE (ChlVPP-EVA) Regimen • Lymphoma – ChlVPP-EVA-Chlorambucil-Doxorubicin-Etoposide-Prednisolone- Procarbazine-Vinblastine-Vincristine Indication • Hodgkin’s Lymphoma Toxicity Drug Adverse Effect Chlorambucil Gastro-intestinal disturbance Doxorubicin Cardiomyopathy, alopecia, urinary discolouration (red) Etoposide Hypotension on rapid infusion, hyperbilirubinaemia Weight gain, gastro-intestinal disturbances, hyperglycaemia, Prednisolone CNS disturbances, cushingoid changes, glucose intolerance Procarbazine Insomnia, ataxia, hallucinations, headache Vinblastine Peripheral neuropathy, constipation, jaw pain, ileus Vincristine Peripheral neuropathy, constipation, jaw pain, ileus The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Patients diagnosed with Hodgkin’s Lymphoma carry a lifelong risk of transfusion-associated graft versus host disease (TA-GVHD). Where blood products are required these patients must receive only irradiated blood products for life. Local blood transfusion departments must be notified as soon as a diagnosis is made and the patient must be issued with an alert card to carry with them at all times. Monitoring Drugs • FBC, LFTs and U&Es prior to day one and eight of treatment Version 1 (May 2018) Page 1 of 10 Lymphoma- ChlVPP-EVA-Chlorambucil-Doxorubicin-Etoposide-Prednisolone-Procarbazine-Vinblastine-Vincristine Dose Modifications The dose modifications listed are for haematological, liver and renal function and limited drug specific toxicities. Dose adjustments may be necessary for other toxicities as well. In principle all dose reductions due to adverse drug reactions should not be re-escalated in subsequent cycles without consultant approval. It is also a general rule for chemotherapy that if a third dose reduction is necessary treatment should be stopped.
    [Show full text]
  • 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).
    [Show full text]
  • Combination Chemotherapy with Estramustine Phosphate, Ifosfamide and Cisplatin for Hormone-Refractory Prostate Cancer
    Acta Med. Okayama, 2006 Vol. 60, No. 1, pp. 43ﾝ49 CopyrightⒸ 2006 by Okayama University Medical School. Original Article http ://www.lib.okayama-u.ac.jp/www/acta/ Combination Chemotherapy with Estramustine Phosphate, Ifosfamide and Cisplatin for Hormone-refractory Prostate Cancer Haruki Kakua, Takashi Saikaa＊, Tomoyasu Tsushimab, Atsushi Nagaia, Teruhiko Yokoyamaa, Fernando Abarzuaa, Shin Ebaraa, Daisuke Manabea, Yasutomo Nasua, and Hiromi Kumona aDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700ﾝ8558, Japan, and bDepartment of Urology, Medival center of Okayama, Okayama 701-1192, Japan We evaluated the effi ciency and toxicity of estramustine phosphate (ECT), ifosfamide (IFM) and cis- platin (CDDP) combination chemotherapy in twenty-one patients with hormone-refractory prostate cancer (HRPC), for which there is currently no eff ective treatment. Patients received a daily dose of 560 mg ECT in combination with 1.2 g/m2 IFM on days 1 to 5 and 70 mg/m2 CDDP on day 1. This combination therapy was given every 3 to 4 weeks. An objective response of more than 50ｵ reduc- tion in prostate-specifi c antigen was observed in 9 of 18 patients (50ｵ), and a more than 50ｵ reduc- tion in bi-dimensionally measurable soft-tissue lesions was observed in 2 of 7 patients (29ｵ). The median duration of response among the cases showing partial response was 40 weeks, while the median duration of response of overall partial-response plus stable cases was 30 weeks. The median survival duration of all cases was 47 weeks. Toxicity was modest and acceptable. In conclusion, the ECT, IFM and CDDP combination chemotherapy regimen is a viable treatment option for HRPC.
    [Show full text]