トリセノックス注 10mg

添付資料一覧

日本新薬株式会社

1

評価資料

2

第３部

3.2 データ又は報告書

3.2-9 品質に関する文書

1

参考資料

2

第３部

3.1 第３部目次 3.2 データ又は報告書

3.2-1 NDA21-248 Volume Ⅰ 3.2-2 NDA21-248 Volume Ⅱ 3.2-3 NDA21-248 Volume Ⅲ 3.2-4 NDA21-248 Volume Ⅳ 3.2-5 NDA 追加資料 3.2-6 NDA21-248-S003 Volume Ⅰ 3.2-7 NDA21-248-S003 Volume Ⅱ 3.2-8 Expert Report 3.2-10 Annual Report 2003.12.2 3.2-11 CP Pharmaceuticals Limited 検体の長期保存試験 9 箇月迄および加

速試験 6 箇月迄の安定性試験の結果 3.2-12 Certificate of Analysis (water for injection) 2003/03/04

3.3 参考文献 該当文献なし

2

第４部

4.1 第４部目次

4.2 試験報告書（薬理試験） 4.2.1 効力を裏付ける試験

4.2.1-1 Arsenic Trioxide Induces Apoptosis of Myeloid Leukemia Cells by

Activation of Caspases.

著者名：Huang XJ, Wiernik PH, Klein RS, Gallagher RE.

雑誌名：Medical Oncology 1999; 16: 58-64.

4.2.1-2 Arsenic Trioxide Selectively Induces Acute Promyelocytic Leukemia Cell

Apoptosis Via a Hydrogen Peroxide-Dependent Pathway.

著者名：Jing BY, Dai J, Chalmers-Redman RME, Tatton WG, Waxman S.

雑誌名：Blood 1999; 94: 2102-2111.

4.2.1-3 Dithiothreitol Enhances Arsenic Trioxide-Induced Apoptosis in NB4 Cells.

著者名：Gurr JR, Bau DT, Liu F, Lynn S, Jan KY. 雑誌名：Molecular Pharmacology 1999; 56: 102-109.

4.2.1-4 Arsenic Trioxide and Melarsoprol Induce Apoptosis in Plasma Cell Lines

and in Plasma Cells from Myeloma Patients. 著者名：Roussselot P, Labaume S, Marolleau JP, Larghero J, Noguera MH,

Brouet JC, et al. 雑誌名：Cancer Research 1999; 59: 1041-1048.

4.2.1-5 Arsenic-induced PML Targeting onto Nuclear Bodies: Implications or the

Treatment of Acute Promyelocytic Leukemia.

著者名：Zhu J, Koken MHM, Quignon F, Chelbi-Alix MK, Degos L,

Wang ZY, et al.

雑誌名：Proc. Natl. Acad. Sci. USA 1997; 94: 3978-3983.

4.2.1-6 The induction of apoptosis and cell cycle arrest by arsenic trioxide in

lymphoid neoplasms.

著者名：Zhang W, Ohnishi K, Shigeno K, Fujisawa S, Naito K, Nakamura

S, et al.

雑誌名：Leukemia. 1998;12(9):1383-91.

3

4.2.1-7 In Vitro Studies on Cellular and Molecular Mechanisms of Arsenic Trioxide

(As2O3) in the Treatment of Acute-Promyelocytic Leukemia: As2O3 Induces

NB4 Cell Apoptosis With Downregulation of Bcl-2 Expression and

Modulation of PML-RARα/PML Proteins.

著者名：Chen BGQ, Zhu J, Shi XG, Ni JH, Zhang HJ, Si GY et al.

雑誌名：Blood 1996; 88: 1052-1061.

4.2.1-8 Effect of Arsenic Trioxide on Viability, Proliferation, and Apoptosis in

Human Megakaryocytic Leukemia Cell Lines.

著者名：Lu M, Levin J, Sulpice E, Grand AS, Alemany M, Caen JP, et al.

雑誌名：Experimental Hematology 1999; 27: 845-852.

4.2.1-9 Use of Arsenic Trioxide (As2O3) in the Treatment of Acute Promyelocytic

Leukemia (APL): I. As2O3 Exerts Dose-Dependent Dual Effects on APL

Cells.

著者名：Chen BGQ, Shi XG, Tang W, Xiong SM, Zhu J, Cai X et al.

雑誌名：Blood 1997; 89: 3345-3353.

4.2.1-10 The Effects of Arsenic Trioxide in the National Cancer Institute in vitro

Anti-cancer Screen.

著者名：Ralph E., Melvin B, Steven S.

試験番号：Preclinical Project No.150-007 2000.

4.2.1-11 Retinoic Acid and Arsenic Synergize to Eradicate Leukemic Cells in a

Mouse Model of Acute Promyelocytic Leukemia.

著者名：Lallemand-Breitenbach BV, Guillemin MC, Janin A, Daniel MT,

Degos L Kogan SC et al.

雑誌名：Journal of Experimental Medicine 1999; 189; 1043-1052.

4.2.1-12 Arsenic trioxide (As2O3)-induced apoptosis and differentiation in retinoic

acid-resistant acute promyelocytic leukemia model in hGM-CSF-producing

transgenic SCID mice.

著者名：Kinjo K, Kizaki M, Muto A, Fukuchi Y, Umezawa A, Yamato K,

et al.

雑誌名：Leukemia. 2000;14(3):431-8.

4

4.2.2 副次的薬理試験 4.2.2-1 Retinoic acid (RA) and As2O3 treatment in transgenic models of acute

promyelocytic leukemia (APL) unravel the distinct nature of the

leukemogenic process induced by the PML-RARα and PLZF-RARα

oncoproteins.

著者名：Rego EM, He LZ, Warrell RP Jr, Wang ZG, Pandolfi PP.

雑誌名：Proc Natl Acad Sci U S A. 2000;97(18):10173-8.

4.2.2-2 Tissue Factors on Acute Promyelocytic Leukemia and Endothelial Cells are

Differently Regulated by Retinoic Acid, Arsenic Trioxide and

Chemotherapeutic Agents.

著者名：Zhu J, Guo WM, Yao YY, Zhao WL, Pan L, Cai X, et al.

雑誌名：Leukemia 1999; 13: 1062-1070.

4.2.2-3 Arsenic Trioxide and Interferon-α Synergize to Induce Cell Cycle Arrest

and Apoptosis in Human T-cell Lymphotropic Virus Type I-Transformed

Cells.

著者名：Bazarbachi BA, El-Sabban ME, Nasr R, Quignon F, Awaraji C,

Kersual J, et al.

雑誌名：Blood 1999; 93: 278-283.

4.2.3 安全性薬理試験 4.2.3-1 Prolongation of cardiac repolarization by arsenic trioxide.

著者名：Chiang C, Luk H, Wang T, Ding PY.

雑誌名：Blood 2002;100:2249-52.

4.2.4 薬力学的薬物相互作用試験 該当試験なし 4.3 試験報告書（薬物動態試験） 4.3.1 分析法及びバリデーション報告書 該当試験なし 4.3.2 吸収

4.3.2-1 Metabolism of 74As-Labeled Trivalent and Pentavalent Inorganic Arsenic in

Mice.

著者名：Vahter,M., Norin,H.

雑誌名：Environmental Research 1980; 21: 446-457.

5

4.3.2-2 砒素の吸収並びに体内分布に関する研究.

著者名：尾谷 清.

雑誌名：札幌医誌 1957; 11(5-6): 285-294.

4.3.3 分布 4.3.3-1 The Metabolism of Arsenite and Arsenate by the Rat.

著者名：Lerman,S., Clarkson,T.

雑誌名：Fundamental and Applied Toxicology. 1983; 3: 309-314.

4.3.3-2 Arsenic Contamination: Metabolic Effects and Localization in Rats.

著者名：Fuentes,N., Zambrano,F., Rosenmann, M.

雑誌名：Comp. Biochem. Physiol. 1981; 70C: 269-272.

4.3.3-3 Pharmacokinetics of Arsenic Trioxide in the Mouse.

著者名：Brunet C, Luyckx M, Cazin M.

雑誌名：Toxicological European Research 1982; 4: 175-179.

4.3.3-4 Autoradiographic Studies on the Distribution of Arsenic in Mice and

Hamsters Administered 74As-Arsenite or -Arsenate.

著者名：Lindgren A, Vahter M, Dencher L. 雑誌名：Acta Pharmacol. Et toxicol. 1982; 51: 253-265.

4.3.3-5 Effect of Oral Treatment with Bal, DMPS or DMSA Arsenic in Organs of

Mice Injected with Arsenic Trioxide.

著者名：Schafer B, Kreppel H, Reichl FX, Fichtl B, Forth W.

雑誌名：Arch. Toxicol., 1991; Suppl 14: 228-230.

4.3.3-6 Efficacy of Various Dithiol Compounds in Acute As2O3 Poisoning in Mice.

著者名：Kreppel H, Reichl FX, Szinicz L, Fichtl B, Forth W.

雑誌名：Archives of Toxicology 1990; 64: 387-392.

4.3.3-7 Tissue Distribution and Subcellular Binding of Arsenic in Marmoset

Monkeys after Injection of 74As-Arsenite.

著者名：Vahter,M., Marafante,E., Lindgren, A., Dencher, L.

雑誌名：Arch Toxicol. 1982; 51: 65-77.

4.3.3-8 Embryotoxicity of Arsenite and Arsenate: Distribution in Pregnant Mice

and Monkeys and Effects on Embryonic Cells in Vitro.

著者名：Lindgren,A., Danielsson,B.R.G., Dencker, L., Vahter,M.

雑誌名：Acta pharmacol. et toxicol. 1984; 54: 311-320.

6

4.3.3-9 ヒ素代謝に関する研究（第 17 報）ヒ素の胎仔移行、それにおよぼす

解毒剤ならびに飼料の影響に関する研究. 著者名：田中いずみ 雑誌名：日薬理誌. 1976; 72: 673-687.

4.3.4 代謝 4.3.4-1 ラットにおける三酸化ヒ素の代謝と排泄.

著者名：山内博他 雑誌名：産業医学. 1980; 22: 111-121.

4.3.4-2 Urinary Excretion of Arsenic Metabolites after Long-term Oral

Administration of Various Arsenic Compounds to Rats.

著者名：Yoshida K, Inoue Y, Kuroda K, Chen H, Wanibushi H, Fukushima

S et al.

雑誌名：Journal of Toxicology and Environmental Health, Part A. 1998;

179-192.

4.3.4-3 Metabolism and Excretion of Orally Administrated Arsenic Trioxide in the

Hamster.

著者名：Yamauchi H and Yamamura Y.

雑誌名：Toxicology 1985; 34: 113-121.

4.3.4-4 Study of Inorganic Arsenic Methylation by Rat Liver in vitro: Relevance

for the Interpretation of Observations in Man.

著者名：Buchet J and Lauwerys R.

雑誌名：Archives of Toxicology 1985; 57: 125-129.

4.3.4-5 Role of Thiols in the in-vitro Methylation of Inorganic Arsenic by Rat Liver

Cytosol.

著者名：Buchet J and Lauwerys R.

雑誌名：Biochemical Pharmacology 1988; 37: 3149-3153.

4.3.5 排泄

4.3.5-1 Biliary excretion of arsenic in rats, rabbits, and dogs.

著者名：Klaassen,C.D.

雑誌名：Toxicology and Applied Pharmacology. 1974; 29: 447-457.

4.3.6 薬物動態学的薬物相互作用（非臨床）

4.3.6-1 Evaluation of arsenic trioxide as an inhibitor of human cytochrome P450

enzymes in vitro.

著者名：Ogilvie B.W.

報告書：(XenoTech 社) 2000; 57.

7

4.3.6-2 Therapeutic Efficacy of New Dimercaptosuccinic Acid (DMSA) Analogues

in Acute Arsenic Trioxide Poisoning in Mice.

著者名：Kreppel H, Paepcke U, Thiermann H, Szinicz L, Reichl FX,

Singh P, et al.

雑誌名：Arch. Toxicol.1993; 67: 580-585.

4.3.6-3 Effect of Chelating Agents on Biliary Excretion of Arsenic in Perfused

Livers of Guinea Pigs Pretreated with As2O3.

著者名：Reichl FX, Kreppel H, Szinicz L, Muckter H, Fichtl B, Schumann

K et al.

雑誌名：Vet Hum Toxicol 1990; 32(3): 223-226.

4.3.7 その他の薬物動態試験

4.3.7-1 Arsenic speciation in human organs following fatal arsenic trioxide

poisoning – a case report.

著者名：Benramdane, L., Acccominotti, M., Fanton, L., Mailicier, D.,

Vallon, J.J.

雑誌名：Clin. Chem. 1999; 45: 301-306.

4.3.7-2 Comparison of the urinary excretion of arsenic metabolites after a single

oral dose of sodium arsenite, monomethylarsonate, or dimethylarsinate in

man.

著者名：Buchet, J.P., Lauwerys, R., Roels, H.

雑誌名：Int. Arch. Occup. Environ. Health. 1981; 48: 71-79.

4.3.7-3 Arsenic levels in blood, urine, hair and nails from a chronically exposed

human population.

著者名：Olguin, A., Jauge, P., Gebrian, M., Albores, A.

雑誌名：Proc. West. Pharmacol. Soc. 1983; 26: 175-177.

4.4 試験報告書（毒性試験） 4.4.1 単回投与毒性試験

4.4.1-1 Action of Adrenal Hormones on Lethal Toxicities of Certain Organic

Compounds.

著者名：Beck,L.V.

雑誌名：Proceeding of the Society for Experimental Biology and

Medicine 1951; 78: 392-397.

8

4.4.1-2 Acute Oral Toxicity and Chemical and Physical Properties of Arsenic

Trioxides.

著者名：Hrrisson,J.W.,Packman,E.W. and Abbott,D.D.

雑誌名：A.M.A.Arch.Indust.Health 1958; 17: 118-123.

4.4.1-3 Comparative acute systemic toxicity of sodium arsenite and

dichloro(2-chlorovinyl) arsine in rabbits.

著者名：Inns R H, Bright J E, Marrs T C

雑誌名：Toxicology 1988; 51: 213-222.

4.4.2 反復投与毒性試験

4.4.2-1 Oxygen Consumption by Mouse Liver Homogenate Drinking Water

Arsenic Exposure.

著者名： Bencko V.

雑誌名：J.Hygiene Epidemiology Microbiology and Immunology 1972;

16: 42-46.

4.4.2-2 Toxic Effect of Arsenic Trioxide in Infant Rats.

著者名：Sigehiro Kiyono, Keiko Hasui, Kazuko Takasu and Misako Seo.

雑誌名：J.Physiol.Soc.Japan 1974; 36: 253-254.

4.4.2-3 Experimental Report on the Toxicity of Repeated Arsenic Trioxide

Injection in Rats.

著者名：Sun Shankui, Yuan Shuhua and He Xiaomin.

雑誌名：Pharmacology Department of Harbin Medical School Report

1998 March.

4.4.2-4 Assessment of Chemicals Using a Battery of Neurobehavioral Tests: A

Comparative Study.

著者名：Pryor,G.T., E.T.Uyeno, H.A.Tilson and C.L.Mitchell.

雑誌名：Neurobehav.Toxicol.Teratol 1983; 5: 91-117.

4.4.2-5 Failure to Produce Arsenic Neurotoxicity in the Rat. An Experimental

Study, Institute of Neurotoxicology.

著者名：Herbert H. Schaumburg.

雑誌名：Albert Einstein College of Medicine New York 1980 May.

4.4.2-6 Pathologic Changes in Rats and Dogs from Two-year Feeding of Sodium

Arsenite or Sodium Arsenate.

著者名：Byron W. R., G. W. Bierbower, J. B. Brouwer, and W. H. Hansen.

9

雑誌名：Toxicol.Appl.Pharmacol 1967; 10: 132-147.

4.4.2-7 Study on Chronic Toxicity of Arsenic Trioxide in Rats with Special

Reference to the Liver Damages.

著者名：Noburu Ishinishi, Masako Tomita and Akira Hisanaga.

雑誌名：Fukuoka Acta Med. 1980; 71: 27-40.

10

4.4.2-8 Toxicity Test of Arsenic Trioxide Solution Intravenously Administered into

Beagle Dogs for 90 Days.

著者名：Peizhong Li, Conglin Zuo and Yuxia Feng.

実施施設・発表時期：The Center of New Drug Development in Zhaoyan,

Beiling, 1998; July.

4.4.2-9 Arsenic Intoxication in the Rhesus Monkey.

著者名：Heywood, R. and R. J. Sortwell.

雑誌名：Toxicol.Letters 1979; 3: 137-144.

4.4.3 遺伝毒性試験

4.4.3.1 In Vitro 試験

4.4.3.1-1 Mutagenic Activites of Metal Componds in Bacteria.

著者名：Nishioka, H.

雑誌名：Mutat. Res. 1975; 31: 185-189.

4.4.3.1-2 Rec Assay and Mutagenicity Studies on Metal Compounds.

著者名：Kanematsu, N., Hara, M. and Kada, T.

雑誌名：Mutat. Res. 1980; 77: 109-116.

4.4.3.1-3 Bacterial Reverse Mutation Assay of Arsenic Trioxide with an Independent

Repeat Assay.

著者名：Wagner, V.O.

報告書：Final Report in BioReliance. Study No. AA36CE.502002.BTL.

2001.

4.4.3.1-4 Mutagenicity of Metal Salts in the L5178Y Mouse Lympohma Assay.

著者名：Oberly, T. J., Piper, C. E. and McDonald, D. S.

雑誌名：J. Toxicol. Environ. Health. 1982; 9: 367-376.

4.4.3.1-5 Comparison of Arsenic-Induced Cell Transformation, Cytotoxicity,

Mutation and Cytogenetic Effects in Syrian Hamster Embryo Cells in

Culture.

著者名：Lee, T. C., Oshimura, M. and Barrett, J. C.

雑誌名：Carcinogenesis 1985; 6: 1421-1426.

4.4.3.1-6 Mechanism of Comutagenesis of Sodium Arsenite with

n-Methyl-n-nitrosourea.

著者名：Li, J. H. and Rossman, T. G.

雑誌名：Biological Trace Element Research 1989; 21: 373-381.

11

4.4.3.1-7 Specificity of Arsenite in Potentiating Cytogentic Damage Induced by the

DNA Crosslinking Agent Diepoxybutane.

著者名：Wiencke, J. K. and Yager, J. W.

雑誌名：Environ. Mol. Mutagen.. 1992; 19: 195-200.

4.4.3.1-8 Arsenite Retards DNA Break Rejoining by Inhibiting DNA Ligation.

著者名：Lynn, S., Lai, H. T., Gurr, J. R. and Jan K. Y.

雑誌名：Mutagenesis 1997; 12: 353-358.

4.4.3.2 In Vivo 試験

4.4.3.2-1 In vivo Studies in Male Mice on the Mutagenic Effects of Inorganic

Arsenic.

著者名：Deknudt, Gh., Leonard, A. Arany, J., Jenar-du Buisson, G. and

Delavignette, E.

雑誌名：Mutagenesis 1986; 1: 33-34.

4.4.3.3 その他の試験

4.4.3.3-1 Induction of Gene Amplification by arsenic.

著者名：Lee, T. C., Tanaka, N., Lamb, P. W., Gilmer, T. M. and Barrett, C.

雑誌名：Science 1988; 241: 79-81.

4.4.3.3-2 Inhibition of DNA Ligase Activity by Arsenite: a Possible Mechanism of its

Comutagenesis.

著者名：Li, J. H. and Rossman, T. G.

雑誌名：Mol. Toxicol. 1989; 2: 1-9.

4.4.3.3-3 Association of Arsenic-induced Malignant Transformation with DNA

Hypomethylation and Aberrant Gene Expression.

著者名：Zhao, C. Q., Young, M. R., Diwan, B. A., Coogan, T. P. and

Waalkes, M. P.

雑誌名：Proc. Natl. Acad. Sci. 1997; 94: 10907-10912.

4.4.3.3-4 Arsenic Alters Cytosine Methylation Patterns of the Promoter of the Tumor

Suppresor Gene p53 in Human Lung Cells: a Model for a Mechanism of

Carcinogenesis.

著者名：Mass, M. J. and Wang, L.

雑誌名：Mutat. Res 1997; 386: 263-277.

12

4.4.4 がん原性試験

4.4.4.1 長期がん原性試験

4.4.4.1-1 Life Term Studies on the Effects of Arsenic, Germanium, Tin, and

Vanadium on Spontaneous Tumors in Mice.

著者名：Masayoshi Kanisawa and Henry, A. Schroeder.

雑誌名：Cancer Research 1967; 27: 1192-1195.

4.4.4.1-2 Life Term Studies on the Effects of Trace Elements on Spontaneous

Tumors in Mice and Rats.

著者名：Masayoshi Kanisawa and Henry, A. Schroeder.

雑誌名：Cancer Research 1969; 29: 892-895.

4.4.4.2 短期又は中期がん原性試験

該当試験なし

4.4.4.3 その他の試験

4.4.4.3-1 Tumorigenicity of Arsenic Trioxide to the Lung in Syrian Golden Hamsters

by Intermittent Instillations.

著者名：Noburu Ishinishi, Akiyo Yamamoto, Akira Hisanaga and Takeo

Inamasu.

雑誌名：Cancer Letters 1983; 21: 141-147.

4.4.4.3-2 Carcinomas of the Respiratory Tract in Hamsters Given Arsenic Trioxide

and/or Benzo[α]pyrene by the Pulmonary Route.

著者名：Goran Pershagen, Gunnar Nordberg and Nils-Erik Bjorklund.

雑誌名：Environmental Research 1984; 34: 227-241.

4.4.5 生殖発生毒性試験

4.4.5.1 受胎能及び着床までの初期胚発生に関する試験

4.4.5.1-1 Absence of Prenatal Developmental Toxicity from Inhaled Arsenic

Trioxide in Rats.

著者名：Holson J. F., Stump D. G., Ulrich C. E. and Farr C. H.

雑誌名：Toxicol.Sci. 1999; 51: 87-97.

4.4.5.1-2 Evaluation of the Prenatal Developmental Toxicity of Orally Administered

Arsenic Trioxide in Rats.

著者名：Holson J. F., Stump D. G., Clevidence K. J., Knapp J. F. and Farr

C. H.

雑誌名：Food and Chemical Toxicology 2000; 38: 459-466.

13

4.4.5.2 胚・胎児発生に関する試験

4.4.5.2-1 Prenatal Toxicity of Orally Administered Sodium Arsenite in Mice.

著者名：Baxley M. N., Hood R. D., Vedel G. C., Harrison W. P. and

Szczech G. M.

雑誌名：Bull. Environm. Contam. Toxicol. 1981; 26: 749-756.

4.4.5.2-2 Evaluation of the Effect of BAL(2,3-Dimercaptopropanol) on

Arsenite-induced Teratogenesis in Mice.

著者名：Hood R. D. and Vedel-Macrander G. C.

雑誌名：Toxicol.Appl.Pharmacol. 1984; 73: 1-7.

4.4.5.2-3 Developmental Toxicity Assessment of Arsenic Acid in Mice and Rabbits.

著者名：Nemec M. D., Holson J. F., Farr C. H. and Hood R. D.

雑誌名：Reprod.Toxicology 1998; 12: 647-658.

4.4.5.2-4 Comparative Effects of Single Intraperitoneal or Oral Doses of Sodium

Arsenate or Arsenic Trioxide During in Utero Development.

著者名：Stump D. G., Holson J. F., Fleeman T. L., Nemec M. D. and Farr

C. H.

雑誌名：Teratology 1999; 60: 283-291.

4.4.5.2-5 Effects of Prenatal Arsenite Exposure in the Hamster.

著者名：Hood R. D. and Harrison W. P.

雑誌名：Bull.Environm.Contam.Toxicology 1982; 29: 671-678.

4.4.5.3 出生前及び出生後の発生並びに母体の機能に関する試験

4.4.5.3-1 Effects of Chronic Prenatal Exposure to Sodium Arsenite on Mouse

Development and Behavior.

著者名：Earnest N. M. and Hood R. D.

出典：Abstract from the Behavioral Teratology Society: Second Annual

Meeting 1981; 24: 53A.

14

第５部

5.1 第５部目次 5.2 臨床試験一覧表 5.3 試験報告書及び関連情報

Clinical Document Part Ⅳ

IV.A Clinical Pharmacology IV.A.1 Pharmacodynamics IV.A.1.1 Electrocardiographic Summary IV.A.1.2 Electrocardiography Report IV.A.2 Clinical Pharmacokinetics IV.A.2.1 Introduction and Overview IV.A.2.1.1 Discussion and Conclusions IV.A.2.1.2 References

Appendix A Summary of Human Pharmacokinetics & Bioavailability Study

Appendix B Study Data Summary IV.A.2.2 Trial Reports IV.A 2.2.1 Study 97-66-PK IV.A 2.2.2 Study 98-23-PK

IV.A. 2.2.3 Study 98-46-PK

IV.B Clinicaｌ Experience IV.B.1 Clinical Trials IV.B.1.1 Background and Overview of Clinical Investigation IV.B.1.2 Pivotal Clinical Trials

IV.B.1.2.1 Clinical Trial Report:(Study 97-66)Pilot Study of Arsenic Trioxide in Relapsed or Refractory Acute Promyelocytic Leukemia

IV.B.1.2.2 Clinical Trial Report (Study PLRXAS01) Multicenter Study of Arsenic Trioxide in Relapsed or Refractory Acute Promyelocytic Leukemia

IV.B.1.3 Supportive Clinical Trials

15

IV.B.1.3.1 Clinical Trial Report:(98-13) Extended Therapy for

Treatment of Those Patients with Acute Promyelocytic Leukemia Previously Treated under Protocol 98-66

IV.B.1.3.2 Clinical Trial Report:(PLRXAS02) Extended Therapy for Treatment of Those Patients with Acute Promyelocytic Leukemia Previously Treated under Protocol PLRXAS01

IV.B.1.3.3 Clinical Trial Report(98-23) Dose-Ranging Study of Arsenic Trioxide in Advanced Solid Tumors

IV.B.1.3.4 SAE Report From Studies UARK-98-033, DM98-211 and Compassionate Use Studies

IV.B.2 Post-Marketing Experience IV. B.3 Published and Other Unpublished References IV.B.3.1 Clinical Reports from the Literature IV.B.3.2 Brief Information on On-Going Trials and

Uncompleted Trials Clinical Trials

5.4 参考文献 5.4-1 Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic

leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed

patients.

著者名：Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, et al.

雑誌名：Blood 1997;89(9):3354-3360.

5.4-2 Enzymatic methylation of arsenic species and other new approaches to

arsenic toxicity.

著者名：Aposhian HV.

雑誌名：Annu Rev Pharmacol Toxicol 1997;37:397-419.

5.4-3 Liberation and analysis of protein-bound arsenicals.

著者名：Styblo M, Hughes MF, Thomas DJ.

雑誌名：J Chromatogr B Biomed Appl 1996;677(1):161-166.

5.4-4 Study of arsenic-protein binding in serum of patients on continuous

ambulatory peritoneal dialysis.

著者名：Zhang X, Cornelis R, de Kimpe J, Mees L, Lameire N.

雑誌名：Clin Chem 1998;44(1):141-147.

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5.4-5 Toxic effects of metals.

著者名：Goyer RA.

出典名：Casarett and Doull’s Toxicology: The Basic Science of Poisons,

5th edition. Klaassen CD, ed. McGraw-Hill: New York. pp.

691-736.

5.4-6 Heavy metals and heavy-metal antagonists.

著者名：Klaasen CD.

出典名 Goodman and Gilman’s The Pharmacological Basis of

therapeutics, 9th edition. Hardman JG, Lembird LE, Molinoff

PB, Ruddon RW, Gilman AG eds. McGraw-Hill:New York. pp.

1649-1671.

5.4-7 Human retention studies with 74As.

著者名：Pomroy C, Charbonneau SM, McCullough RS, Tam GK.

雑誌名：Toxicol Appl Pharmacol 1980;53(3):550-6.

5.4-8 Experiments on excretion of arsenic in urine.

著者名：Mappes R.

雑誌名：Int Arch Occup Environ Health 1977;40:267-272.

5.4-9 Urinary excretion of inorganic arsenic and its metabolites after repeated

ingestion of sodium metaarsenite by volunteers.

著者名：Buchet.JP, Lauwerys R, Roels H.

雑誌名：Int Arch Occup Environ Health 1981;48:111-118.

5.4-10 Phase I Trial and Pharmacokinetic Study of Arsenic Trioxide in Children

with Refractory Leukemia.

著者名：Fox E, Adamson PC, Murgo A, Letterio J, O'Brien M, Goodspeed

W, et al.

出典名：Presented at ASCO Annual Meeting, May 18-21, 2002, in

Orlando, Florida.

5.4-11 急性前骨髄球性白血病の治療に用いた亜ヒ酸の有効性と生体内動態

～ヒト生体内試料中のヒ素の化学形態別分析～［演題番号：Ⅱ-648］

著者名：深井康臣，太田伸，上野真由美，斉藤博，平田美由紀，古

庄義明，他． 出典名：日本薬学会第 123 年会講演要旨集 2003;4:150

5.4-12 Inorganic Arsenic Metabolism in Man.

著者名：Buchet.JP, Lauwerys R, Mahieu P, Geubel A.

雑誌名：Arch Toxicol 1982;Suppl 5:326-327.

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5.4-13 Complete Remission After Treatment of Acute Promyelocytic Leukemia

with Arsenic Trioxide.

著者名：Soignet SL, Maslak P, Wang Z, Jhanwar S, Calleja E, Dardashti

LJ, et al.

雑誌名：The New England Journal of Medicine 1998; 339: 1341-1348.

5.4-14 United States Multicenter Study of Arsenic Trioxide in Relapsed Acute

Promyelocytic Leukemia.

著者名：Soignet SL, Frankel SR, Douer D, Tallman MS, Kantarjian H, et

al.

雑誌名：Journal of Clinical Oncology 2001; 19: 3852-3860.

5.4-15 Molecular remission induction with retinoic acid and anti-CD33

monoclonal antibody HuM195 in acute promyelocytic leukemia.

著者名：Jurcic JG, de Blasio T, Dumont L, Yao TJ, Scheinberg DA.

雑誌名：Clin Cancer Res 2000;6(2):372-80.

5.4-16 Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic

acid therapy followed by timed sequential chemotherapy and stem cell

transplantation. APL Study Group. Acute promyelocytic leukemia.

著者名：Thomas X, Dombret H, Cordonnier C, Pigneux A, Gardin C,

Guerci A, et al.

雑誌名：Leukemia 2000;14(6):1006-1013.

5.4-17 Studies on the clinical efficacy and pharmacokinetics of low-dose arsenic

trioxide in the treatment of relapsed acute promyelocytic leukemia: a

comparison with conventional dosage.

著者名：Shen Y, Shen Z, Yan H, Chen X, Zeng X, Li J, et al.

雑誌名：Leukemia 2001;15:735-741.

5.4-18 Updated safety experience with Trisenox (arsenic trioxide) injection.

[Abstract #4540]

著者名：Paradise C, Ellison R, Kirkhart B, Singer JW.

雑誌名：Blood 2002; 100:254b.

5.4-19 三酸化ヒ素の過血糖作用に関する薬理学的研究.

著者名：川口いずみ

雑誌名：日薬理誌 1981; 78: 213-222.

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参考資料

参考資料１ 浜松医科大学治療研究における投稿論文(1)及び正誤表

表題：Arsenic trioxide therapy for relapsed or refractory Japanese

patients with acute promyelocytic leukemia: need for careful

electrocardiogram monitoring.

著者名：Ohnishi K, Yoshida H, Shigeno K, Nakamura S, Fujisawa S,

Naito K, et al.

雑誌名：Leukemia 2002;16(4):617-622.

参考資料２ 浜松医科大学治療研究・計画書

参考資料３ 浜松医科大学治療研究症例報告書

参考資料４ 浜松医科大学治療研究症例一覧表

参考資料５ 信頼性調査改善確認書

参考資料６ 浜松医科大学治療研究における投稿論文(2)

表題：Prolongation of the QT interval and ventricular tachycardia in

patients treated with arsenic trioxide for acute promyelocytic

leukemia.

著者名：Ohnishi K, Yoshida H, Shigeno K, Nakamura S, Fujisawa S,

Naito K, et al.

雑誌名：Ann Intern Med 2000;133(11):881-885.

参考資料７ 欧州医薬品審査庁 Trisenox 審査報告書

参考資料８ 米国食品医薬局 Trisenox 審査報告書

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