How Chemotherapy Drugs Work
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RESEARCH ARTICLE Lobaplatin Combined Floxuridine/Pirarubicin
DOI:http://dx.doi.org/10.7314/APJCP.2014.15.5.2057 The Effect Observation of LBP-based TACE for Unresectable Primary Hepatocellular Carcinoma RESEARCH ARTICLE Lobaplatin Combined Floxuridine/Pirarubicin-based Transcatheter Hepatic Arterial Chemoembolization for Unresectable Primary Hepatocellular Carcinoma Chang Zhao1, Xu-Jie Wang2*, Song Wang2*, Wei-Hua Feng2, Lei Shi2, Chun- Peng Yu2 Abstract Purpose: To assess the effect and safety of lobaplatin combinated floxuridine /pirarubicin in transcatheter hepatic arterial chemoembolization(TACE) of unresectable primary liver cancer. Patients and Methods: TACE combined with the chemotherapy regimen was used to treat 34 unresectable primary liver cancer patients. DSA/ MRI/CT/blood routine examinations were used to evaluate short term activity and toxicity after 4-5 weeks, the process being repeated if necessary. Results: Among the 34 cases, 1 (2.9%) showed a complete response, 21 (61.7%) a partial response, 8 (23.5%) stable disease, and 4 progressive disease, with a total effective rate of 67.6%. The content of alpha fetoprotein dropped by over 50% in 20 cases (58.8%). The rate of recovery was hepatalgia (88.2%), ascites (47.1%), appetite (55.9%), Performance Status(30.4%). The median follow-up time (MFT) was 281 days (63-558 days), and median progression-free survival was 118.5 days (95%, CI:88.8-148.2days). Adverse reactions (III-IV grade) were not common, with only 4 cases of vomiting and 2 cases of thrombocytopenia (III grade). Conclusions: Lobaplatin-based TACE is an effective and safe treatment for primary liver cancer. Keywords: Primary hepatic carcinoma - chemoembolization - platinum chemotherapy - clinical response Asian Pac J Cancer Prev, 15 (5), 2057-2060 Introduction LBP-based TACE, male 29 cases, female 5 cases, average age for 57.2±10.7 years, 12 cases were biopsy-proven, Hepatocellular carcinoma (HCC) is a common 22 cases were in line with the China Cancer Association malignant tumor . -
Cancer Drug Pharmacology Table
CANCER DRUG PHARMACOLOGY TABLE Cytotoxic Chemotherapy Drugs are classified according to the BC Cancer Drug Manual Monographs, unless otherwise specified (see asterisks). Subclassifications are in brackets where applicable. Alkylating Agents have reactive groups (usually alkyl) that attach to Antimetabolites are structural analogues of naturally occurring molecules DNA or RNA, leading to interruption in synthesis of DNA, RNA, or required for DNA and RNA synthesis. When substituted for the natural body proteins. substances, they disrupt DNA and RNA synthesis. bendamustine (nitrogen mustard) azacitidine (pyrimidine analogue) busulfan (alkyl sulfonate) capecitabine (pyrimidine analogue) carboplatin (platinum) cladribine (adenosine analogue) carmustine (nitrosurea) cytarabine (pyrimidine analogue) chlorambucil (nitrogen mustard) fludarabine (purine analogue) cisplatin (platinum) fluorouracil (pyrimidine analogue) cyclophosphamide (nitrogen mustard) gemcitabine (pyrimidine analogue) dacarbazine (triazine) mercaptopurine (purine analogue) estramustine (nitrogen mustard with 17-beta-estradiol) methotrexate (folate analogue) hydroxyurea pralatrexate (folate analogue) ifosfamide (nitrogen mustard) pemetrexed (folate analogue) lomustine (nitrosurea) pentostatin (purine analogue) mechlorethamine (nitrogen mustard) raltitrexed (folate analogue) melphalan (nitrogen mustard) thioguanine (purine analogue) oxaliplatin (platinum) trifluridine-tipiracil (pyrimidine analogue/thymidine phosphorylase procarbazine (triazine) inhibitor) -
In Vitro and in Vivo Reversal of Resistance to 5-Fluorouracil in Colorectal Cancer Cells with a Novel Stealth Double-Liposomal Formulation
British Journal of Cancer (2007) 97, 919 – 926 & 2007 Cancer Research UK All rights reserved 0007 – 0920/07 $30.00 www.bjcancer.com In vitro and in vivo reversal of resistance to 5-fluorouracil in colorectal cancer cells with a novel stealth double-liposomal formulation 1 1 1 1 2 3 *,1 R Fanciullino , S Giacometti , C Mercier , C Aubert , C Blanquicett , P Piccerelle and J Ciccolini 1 2 EA3286-Laboratoire de Pharmacocine´tique, Universite´ de la Me´diterrane´e, Marseille, France; Department of Medicine, School of Medicine, Emory 3 University, Atlanta, GA, USA; Laboratoire de Pharmacie Gale´nique, Faculte´ de Pharmacie, 27 Bd Jean Moulin, Marseille 05 13385, France Drug resistance is a major cause of treatment failure in cancer chemotherapy, including that with the extensively prescribed antimetabolite, 5-fluorouracil (5-FU). In this study, we tried to reverse 5-FU resistance by using a double-punch strategy: combining 5-FU with a biochemical modulator to improve its tumoural activation and encapsulating both these agents in one same stealth liposome. Experiments carried out in the highly resistant, canonical SW620 human colorectal model showed a up to 80% sensitisation to 5-FU when these cells were treated with our liposomal formulation. Results with this formulation demonstrated 30% higher tumoural drug uptake, better activation with increased active metabolites including critical-5-fluoro-2-deoxyuridine-5-monophos- phate, superior inhibition (98%) of tumour thymidylate synthase, and subsequently, higher induction of both early and late apoptosis. Drug monitoring showed that higher and sustained exposure was achieved in rats treated with liposomal formulation. When examined in a xenograft animal model, our dual-agent liposomal formulation caused a 74% reduction in tumour size with a mean doubling in survival time, whereas standard 5-FU failed to exhibit significant antiproliferative activity as well as to increase the lifespan of tumour-bearing mice. -
The Synergic Effect of Vincristine and Vorinostat in Leukemia in Vitro and In
Chao et al. Journal of Hematology & Oncology (2015) 8:82 DOI 10.1186/s13045-015-0176-7 JOURNAL OF HEMATOLOGY & ONCOLOGY RESEARCH ARTICLE Open Access The synergic effect of vincristine and vorinostat in leukemia in vitro and in vivo Min-Wu Chao1, Mei-Jung Lai2, Jing-Ping Liou3, Ya-Ling Chang1, Jing-Chi Wang4, Shiow-Lin Pan4*† and Che-Ming Teng1*† Abstract Background: Combination therapy is a key strategy for minimizing drug resistance, a common problem in cancer therapy. The microtubule-depolymerizing agent vincristine is widely used in the treatment of acute leukemia. In order to decrease toxicity and chemoresistance of vincristine, this study will investigate the effects of combination vincristine and vorinostat (suberoylanilide hydroxamic acid (SAHA)), a pan-histone deacetylase inhibitor, on human acute T cell lymphoblastic leukemia cells. Methods: Cell viability experiments were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and cell cycle distributions as well as mitochondria membrane potential were analyzed by flow cytometry. In vitro tubulin polymerization assay was used to test tubulin assembly, and immunofluorescence analysis was performed to detect microtubule distribution and morphology. In vivo effect of the combination was evaluated by a MOLT-4 xenograft model. Statistical analysis was assessed by Bonferroni’s t test. Results: Cell viability showed that the combination of vincristine and SAHA exhibited greater cytotoxicity with an IC50 value of 0.88 nM, compared to each drug alone, 3.3 and 840 nM. This combination synergically induced G2/M arrest, followed by an increase in cell number at the sub-G1 phase and caspase activation. -
Evaluation of Floxuridine Oligonucleotide Conjugates Carrying Potential Enhancers of Cellular Uptake
International Journal of Molecular Sciences Article Evaluation of Floxuridine Oligonucleotide Conjugates Carrying Potential Enhancers of Cellular Uptake Anna Aviñó 1,2,*, Anna Clua 1,2 , Maria José Bleda 1 , Ramon Eritja 1,2,* and Carme Fàbrega 1,2 1 Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain; [email protected] (A.C.); [email protected] (M.J.B.); [email protected] (C.F.) 2 Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Jordi Girona 18-26, E-08034 Barcelona, Spain * Correspondence: [email protected] (A.A.); [email protected] (R.E.); Tel.: +34-934-006-100 (A.A.) Abstract: Conjugation of small molecules such as lipids or receptor ligands to anti-cancer drugs has been used to improve their pharmacological properties. In this work, we studied the biological effects of several small-molecule enhancers into a short oligonucleotide made of five floxuridine units. Specifically, we studied adding cholesterol, palmitic acid, polyethyleneglycol (PEG 1000), folic acid and triantennary N-acetylgalactosamine (GalNAc) as potential enhancers of cellular uptake. As expected, all these molecules increased the internalization efficiency with different degrees depending on the cell line. The conjugates showed antiproliferative activity due to their metabolic activation by nuclease degradation generating floxuridine monophosphate. The cytotoxicity and apoptosis assays showed an increase in the anti-cancer activity of the conjugates related to the floxuridine oligomer, but this effect did not correlate with the internalization results. Palmitic and folic acid conjugates provide the highest antiproliferative activity without having the highest internalization Citation: Aviñó, A.; Clua, A.; Bleda, results. -
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 -
Floxuridine | Memorial Sloan Kettering Cancer Center
PATIENT & CAREGIVER EDUCATION Floxuridine This information from Lexicomp® explains what you need to know about this medication, including what it’s used for, how to take it, its side effects, and when to call your healthcare provider. Warning This drug may cause unsafe effects. You will be closely watched when starting this drug. What is this drug used for? It is used to treat cancer. What do I need to tell my doctor BEFORE I take this drug? If you are allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had. If you have any of these health problems: Poor nutrition, an infection, or certain bone marrow problems like low white blood cell count, low platelet count, or low red blood cell count. If you are breast-feeding. Do not breast-feed while you take this drug. Floxuridine 1/7 This is not a list of all drugs or health problems that interact with this drug. Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor. What are some things I need to know or do while I take this drug? Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists. -
Emetogenic Potential of Antineoplastic Agents
EMETOGENIC POTENTIAL OF ANTINEOPLASTIC AGENTS High Risk (>90% frequency without antiemetics) • AC combination: Doxorubicin or Epirubicin (Ellence) ϩ • Doxorubicin IV: >60mg/m 2 Cyclophosphamide (Cytoxan) IV • Epirubicin (Ellence) IV: >90mg/m 2 • Altretamine (HMM, Hexalen) oral • Ifosfamide (Ifex) IV: Ն2g/m 2 per dose • Carmustine (BCNU, BiCNU) IV: Ͼ250mg/m 2 • Mechlorethamine (Mustargen) IV • Cisplatin (CDDP) IV • Procarbazine (Matulane) oral • Cyclophosphamide (CTX, Cytoxan) IV: Ͼ1,500mg/m 2 • Streptozocin (Zanosar) IV • Dacarbazine (DTIC, DTIC-Dome) IV Moderate Risk (30–90% frequency without antiemetics) 2 2 • Aldesleukin (IL-2, Proleukin) IV: Ͼ12–15 million IU/m • Doxorubicin IV: Յ60mg/m 2 2 • Amifostine (Ethyol) IV: Ͼ300mg/m • Epirubicin (Ellence) IV: Յ90mg/m • Arsenic trioxide (As2 O3 , Trisenox) IV • Estramustine (Emcyt) oral • Azacitidine (Vidaza) IV • Etoposide (VP-16) oral • Bendamustine (Treanda) IV • Idarubicin (Idamycin) IV • Busulfan (Busulfex) IV ; oral: Ͼ4mg/day • Ifosfamide (Ifex) IV: Ͻ2g/m 2 • Carboplatin IV • Interferon alpha (IFN-alfa, Intron A) IV: Ն10 million IU/m 2 • Carmustine (BCNU, BiCNU) IV: Յ250mg/m 2 • Irinotecan (CPT-11, Camptosar) IV • Clofarabine (Clolar) IV • Lomustine (CCNU, CeeNU) oral • Cyclophosphamide (CTX, Cytoxan) IV: Յ1,500mg/m 2 • Melphalan (L-PAM, Alkeran) IV • Cyclophosphamide (CTX) oral Ն100mg/m 2 /day • Methotrexate (MTX) IV: Ն250mg/m 2 • Cytarabine (ARA-C) IV: Ͼ200mg/m 2 • Oxaliplatin (Eloxatin) IV • Dactinomycin (Cosmegen) IV • Temozolomide (Temodar) IV; oral Ͼ75mg/m 2 /day • Daunorubicin -
Original New Drug Applications
New Drugs Reviewed by CPG January 23, 2017 (Original New Drug Applications: FDA) Generic Name Trade Name Indication(s) CPG Action Immune globulin Cuvitru Biologic and In accordance with subcutaneous Immunological the SCA [human] 20% solution Agents/Immune Globulins/ Immune Globulin (Human) subcutaneous. Indicated as replacement for primary humoral immunodeficiency in adult and pediatric patients age two and older. eteplirsen Exondys 51 Central Nervous System In accordance with Agents/Antisense the SCA Oligonucleotides. Treatment of patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. First drug approved for reatment of patients with Duchenne muscular dystrophy. levonorgestrel- Kyleena Endocrine and May prescribe releasing intrauterine Metabolic Agents/sex system 19.5 mg homones/contraceptive Hormones. Prevention of pregnancy for up to five years. **Phentermine Lomaira Central Nervous System In accordance with hydrochloride 8 mg Agents/ the SCA anorexiants/sympathomi metic anorexiants. Short term use weight reduction in adults with **(new formulation at an initial BMI of 30 or lower dosage) more or 27 with at least one weight-related condition. 1 New Drugs January 2017 canaglifozin/ Invokamet XR Endocrine and May prescribe metformin HCL Metabolic Agents/ extended-release antidiabetic agents/antidiabetic combination products. Treatment of adults with type 2 diabetes as an adjunct to diet and exercise. Adalimumab-atto Amjevita Biologic and In accordance with Immunological Agents/ the SCA Immunologic Agents/Immunomodulat ors/Tumor necrosis Factor-Alpha Blockers. Indicated for treatment of adults with: rheumatoid arthritis, psoriatic arthritis,ankylosing spondylitis, Crohn disease, ulcerative colitis, and plaque psoriasis. Also indicated for juvenile idiopathic arthritis in pts age 4 years and older. -
Prodrugs: a Challenge for the Drug Development
PharmacologicalReports Copyright©2013 2013,65,1–14 byInstituteofPharmacology ISSN1734-1140 PolishAcademyofSciences Drugsneedtobedesignedwithdeliveryinmind TakeruHiguchi [70] Review Prodrugs:A challengeforthedrugdevelopment JolantaB.Zawilska1,2,JakubWojcieszak2,AgnieszkaB.Olejniczak1 1 InstituteofMedicalBiology,PolishAcademyofSciences,Lodowa106,PL93-232£ódŸ,Poland 2 DepartmentofPharmacodynamics,MedicalUniversityofLodz,Muszyñskiego1,PL90-151£ódŸ,Poland Correspondence: JolantaB.Zawilska,e-mail:[email protected] Abstract: It is estimated that about 10% of the drugs approved worldwide can be classified as prodrugs. Prodrugs, which have no or poor bio- logical activity, are chemically modified versions of a pharmacologically active agent, which must undergo transformation in vivo to release the active drug. They are designed in order to improve the physicochemical, biopharmaceutical and/or pharmacokinetic properties of pharmacologically potent compounds. This article describes the basic functional groups that are amenable to prodrug design, and highlights the major applications of the prodrug strategy, including the ability to improve oral absorption and aqueous solubility, increase lipophilicity, enhance active transport, as well as achieve site-selective delivery. Special emphasis is given to the role of the prodrug concept in the design of new anticancer therapies, including antibody-directed enzyme prodrug therapy (ADEPT) andgene-directedenzymeprodrugtherapy(GDEPT). Keywords: prodrugs,drugs’ metabolism,blood-brainbarrier,ADEPT,GDEPT -
SUPPLEMENTARY FILE Cellular Fitnessphenotype of Cancer Target
SUPPLEMENTARY FILE Cellular FitnessPhenotype of Cancer Target Genes in Cancer Therapeutics Bijesh George, P. Mukundan Pillai, Aswathy Mary Paul, Revikumar Amjesh, Kim Leitzel, Suhail M. Ali, Oleta Sandiford, Allan Lipton, Pranela Rameshwar, Gabriel N. Hortobagyi, Madhavan Radhakrishna Pillai, and Rakesh Kumar Supplementary Figures Supplementary Figure S1: Fitness-dependency of cellular targets of approved oncology drugs in cancer cell lines. A, Distribution of alterations in the cellular fitness in esophageal cancer cell lines upon selective knockdown of FSPS test gene. The values are plotted as boxplots with positive and negative changes in the cellular fitness for each cell line, represented by a single dot. B, Effect of knocking down of indicated targets in Head and Neck carcinoma cell lines. C, Distribution of 47 cancer targets of FDA-approved drugs, including, a subset of its 15 priority therapeutic targets in across cancer- types for which drugs targeting these cellular targets are approved. D, Distribution of 47 fitness targets across 19 cancer types for which drugs targeting these molecules are approved corresponds to the loss of Fitness score for were taken from Cancer Dependency Map (23). Supplementary Figure S2: Cellular targets of approved oncology drugs as excellent fitness genes in cancer-types for which drugs targeting these are not approved. Distribution of 43 cellular fitness genes with a significant loss of cellular fitness upon their depletion across peripheral nervous system, large intestine and ovarian cell lines -
Process for Producing Arsenic Trioxide Formulations
(19) TZZ_964557B_T (11) EP 1 964 557 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/285 (2006.01) A61K 33/36 (2006.01) 02.01.2013 Bulletin 2013/01 A61P 35/02 (2006.01) (21) Application number: 08075200.9 (22) Date of filing: 10.11.1998 (54) Process for producing arsenic trioxide formulations Verfahren zur Herstellung von Arsentrioxidformulierungen Procédé de production de formulations à base de trioxide d’arsenic (84) Designated Contracting States: (74) Representative: Warner, James Alexander et al AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU Carpmaels & Ransford MC NL PT SE One Southampton Row London (30) Priority: 10.11.1997 US 64655 P WC1B 5HA (GB) (43) Date of publication of application: (56) References cited: 03.09.2008 Bulletin 2008/36 • KWONG Y L ET AL: "Delicious poison: Arsenic trioxide for the treatment of leukemia" BLOOD, (60) Divisional application: vol. 89, no. 9, 1 May 1997 (1997-05-01), pages 10177319.0 / 2 255 800 3487-3488, XP002195910 • SHEN S-X ET AL: "USE OF ARSENIC TRIOXIDE (62) Document number(s) of the earlier application(s) in (AS2O3) IN THE TREATMENT OF ACUTE accordance with Art. 76 EPC: PROMYELOCITIC LEUKEMIA (APL): II. CLINICAL 98957803.4 / 1 037 625 EFFICACY AND PHARMACOKINETICS IN RELAPSED PATIENTS" BLOOD, W.B. (73) Proprietor: MEMORIAL SLOAN-KETTERING SAUNDERS, PHILADELPHIA, VA, US, vol. 89, no. CANCER CENTER 9, 1 May 1997 (1997-05-01), pages 3354-3360, New York, NY 10021 (US) XP000891715 ISSN: 0006-4971 • KONIG ET AL: "Comparative activity of (72) Inventors: melarsoprol and arsenic trioxide in chronic B - • Warrell, Raymond, P., Jr.