第4部（モジュール4）非臨床試験報告書添付資料一覧 4.3 参考 … · Cloning and mRNA expression of vascular endothelial growth factor in ischemic retinas of

CTD No.-資料番号

著者表題実施期間実施場所

（国内／海外）掲載誌・その他

評価／参考の別

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4.3 参考文献第4部（モジュール4）　非臨床試験報告書　添付資料一覧

2.4の参考文献

4.3 参考文献一覧

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Induction of vascular endothelial growth factor geneexpression by interleukin-1β in rat aortic smoothmuscle cells.

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2.6.1-35Cohen T, Nahari D,Cerem LW, Neufeld G,Levi B-Z.

Interleukin 6 induces the expression of vascularendothelial growth factor. ― ― J Biol Chem. 1996; 271:

736-741. 参考

2.6.1-36

Harada S, Nagy JA,Sullivan KA, ThomasKA, Endo N, Rodan GA,et al.

Induction of vascular endothelial growth factorexpression by prostaglandin E2 and E1 in osteoblasts. ― ― J Clin Invest. 1994; 93:

2490-2496. 参考

2.6.1-37Warren RS, Yuan H,Matli MR, Ferrara N,Donner DB.

Induction of vascular endothelial growth factor byinsulin-like growth factor 1 in colorectal carcinoma. ― ― J Biol Chem. 1996; 271:

29483-29488. 参考

2.6.1-38Kieser A, Weich HA,Brandner G, Marmé D,Kolch W.

Mutant p53 potentiates protein kinase C induction ofvascular endothelial growth factor expression. ― ― Oncogene. 1994; 9: 963-

969. 参考

2.6.1-39

Rak J, Mitsuhashi Y,Bayko L, Filmus J,Shirasawa S, Sasazuki T,et al.

Mutant ras oncogenes upregulate VEGF/VPFexpression: implications for induction and inhibition oftumor angiogenesis.

― ― Cancer Res. 1995; 55:4575-4580. 参考

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2.6.1-40Grugel S, Finkenzeller G,Weindel K, Barleon B,Marmé D.

Both v-Ha-Ras and v-Raf stimulate expression of thevascular endothelial growth factor in NIH 3T3 cells. ― ― J Biol Chem. 1995; 270:

25915-25919. 参考

2.6.1-41 Mukhopadhyay D,Tsiokas L, Sukhatme VP.

Wild-type p53 and v-Src exert opposing influences onhuman vascular endothelial growth factor geneexpression.

― ― Cancer Res. 1995; 55:6161-6165. 参考

2.6.1-42

Siemeister G, Weindel K,Mohrs K, Barleon B,Martiny-Baron G, MarméD.

Reversion of deregulated expression of vascularendothelial growth factor in human renal carcinomacells by von Hippel-Lindau tumor suppressor protein.

― ― Cancer Res. 1996; 56:2299-2301. 参考

2.6.1-43 Volm M, Koomägi R,Mattern J, Stammler G.

Angiogenic growth factors and their receptors in non-small cell lung carcinomas and their relationships todrug response in vitro.

― ― Anticancer Res. 1997; 17:99-104. 参考

2.6.1-44Yoshiji H, Gomez DE,Shibuya M, ThorgeirssonUP.

Expression of vascular endothelial growth factor, itsreceptor, and other angiogenic factors in human breastcancer.

― ― Cancer Res. 1996; 56:2013-2016. 参考

2.6.1-45 Mattern J, Koomägi R,Volm M.

Association of vascular endothelial growth factorexpression with intratumoral microvessel density andtumour cell proliferation in human epidermoid lungcarcinoma.

― ― Br J Cancer. 1996; 73:931-934. 参考

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2.6.1-46

Maeda K, Chung YS,Ogawa Y, Takatsuka S,Kang SM, Ogawa M, etal.

Prognostic value of vascular endothelial growth factorexpression in gastric carcinoma. ― ― Cancer. 1996; 77: 858-

863. 参考

2.6.1-47 Volm M, Koomägi R,Mattern J.

Prognostic value of vascular endothelial growth factorand its receptor Flt-1 in squamous cell lung cancer. ― ― Int J Cancer. 1997; 74:

64-68. 参考

2.6.1-48Gasparini G, Toi M, GionM, Verderio P, Dittadi R,Hanatani M, et al.

Prognostic significance of vascular endothelial growthfactor protein in node-negative breast carcinoma. ― ― J Natl Cancer Inst. 1997;

89: 139-147. 参考

2.6.1-49Inoue M, Hager JH,Ferrara N, Gerber H-P,Hanahan D.

VEGF-A has a critical, nonredundant role inangiogenic switching and pancreatic β cellcarcinogenesis.

― ― Cancer Cell. 2002; 1:193-202. 参考

2.6.1-50

Ferrara N, Winer J,Burton T, Rowland A,Siegel M, Phillips HS, etal.

Expression of vascular endothelial growth factor doesnot promote transformation but confers a growthadvantage in vivo to Chinese hamster ovary cells.

― ― J Clin Invest. 1993; 91:160-170. 参考

2.6.2-1

Leunig M, Yuan F,Menger MD, Boucher Y,Goetz AE, Messmer K, etal.

Angiogenesis, microvascular architecture,microhemodynamics, and interstitial fluid pressureduring early growth of human adenocarcinomaLS174T in SCID mice.

― ― Cancer Res. 1992; 52:6553-6560. 参考


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2.6.2-2Yuan F, Salehi HA,Boucher Y, Vasthare US,Tuma RF, Jain RK.

Vascular permeability and microcirculation of gliomasand mammary carcinomas transplanted in rat andmouse cranial windows.

― ― Cancer Res. 1994; 54:4564-4568. 参考

2.6.2-3

Brasch R, Pham C,Shames D, Roberts T, vanDijke K, van Bruggen N,et al.

Assessing tumor angiogenesis using macromolecularMR imaging contrast media. ― ― J Magn Reson Imaging.

1997; 7: 68-74. 参考

2.6.2-4Auerbach R, Lewis R,Shinners B, Kubai L,Akhtar N.

Angiogenesis assays: a critical overview. ― ― Clin Chem. 2003; 49: 32-40. 参考

2.6.2-5Passaniti A, Taylor RM,Pili R, Guo Y, Long PV,Haney JA, et al.

A simple, quantitative method for assessingangiogenesis and antiangiogenic agents usingreconstituted basement membrane, heparin, andfibroblast growth factor.

― ― Lab Invest. 1992; 67:519-528. 参考

2.6.2-6Muller YA, ChristingerHW, Keyt BA, de VosAM.

The crystal structure of vascular endothelial growthfactor (VEGF) refined to 1.93Å resolution: multiplecopy flexibility and receptor binding.

― ― Structure. 1997; 5: 1325-1338. 参考

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2.6.2-7

Muller YA, Li B,Christinger HW, WellsJA, Cunningham BC, deVos AM.

Vascular endothelial growth factor: crystal structureand functional mapping of the kinase domain receptorbinding site.


2.6.2-8

Wiesmann C, Fuh G,Christinger HW,Eigenbrot C, Wells JA, deVos AM.

Crystal structure at 1.7Å resolution of VEGF incomplex with domain 2 of the flt-1 receptor. ― ― Cell. 1997; 91: 695-704. 参考

2.6.2-9 Heldin C-H, Rubin K,Pietras K, Östman A.

High interstitial fluid pressure – an obstacle in cancertherapy. ― ― Nat Rev Cancer. 2004; 4:

806-813 参考

2.6.2-10 Jain RK. Interstitial transport in tumors: barriers and strategiesfor improvement. ― ―

AACR 96th annualmeeting AACREducation Book. 2005;108-113.

参考

2.6.2-11Willett CG, Boucher Y,di Tomaso E, Duda DG,Munn LL, Tong RT, et al.

Direct evidence that the VEGF-specific antibodybevacizumab has antivascular effects in human rectalcancer.

― ― Nat Med. 2004; 10: 145-147. 参考

2.6.4-1Arizono H, Ishii S, NagaoT, Kudo S, Sasaki S,Kondo S, et al.

Pharmacokinetics of a new human monoclonalantibody against cytomegalovirus. ― ― Arzneimittelforschung.

1994; 44: 890-898. 参考


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2.6.4-2

Fox JA, Hotaling TE,Struble C, Ruppel J,Bates DJ, SchoenhoffMB.

Tissue distribution and complex formation with IgE ofan anti-IgE antibody after intravenous administrationin Cynomolgus monkeys.

― ― J Pharmacol Exp Ther.1996; 279: 1000-1008. 参考

2.6.4-3Schoenhoff M, Bates D,Ruppel J, Fei D, Fox JA,Thomas D, et al.

Pharmacokinetics/dynamics following administrationof a recombinant humanized monoclonal anti IgEantibody in the cynomolgus monkey (abstract).

― ― J Allergy Clin Immunol.1995; 95 (1 Pt 2): 356. 参考

2.6.4-4Ghetie V, Hubbard JG,Kim J-K, Tsen M-F, LeeY, Ward ES.

Abnormally short serum half-lives of IgG in β2-microglobulin-deficient mice. ― ― Eur J Immunol. 1996; 26:

690-696. 参考

2.6.4-5 Junghans RP, AndersonCL.

The protection receptor for IgG catabolism is the β2-microglobulin-containing neonatal intestinal transportreceptor.


2.6.4-6Israel EJ, Wilsher DF,Hayes K, Schoenfeld D,Simister NE.

Increased clearance of IgG in mice that lack β2-microglobulin: possible protective role of FcRn. ― ― Immunology. 1996; 89:

573-578. 参考

2.6.4-7 Ghetie V, Ward ES. Multiple roles for the major histocompatibilitycomplex class I-related receptor FcRn. ― ― Annu Rev Immunol.

2000; 18: 739-766. 参考

2.6.4-8 Story CM, Mikulska JE,Simister NE.

A major histocompatibility complex Class I-like Fcreceptor cloned from human placenta: possible role intransfer of immunoglobulin G from mother to fetus.

― ― J Exp Med. 1994: 180;2377-2381. 参考

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2.6.4-9

Borvak J, Richardson J,Medesan C, Antohe F,Radu C, Simionescu M, etal.

Functional expression of the MHC class I-relatedreceptor, FcRn, in endothelial cells of mice. ― ― Int Immunol. 1998; 10:

1289-1298. 参考

2.6.4-10 Henderson LA, BaynesJW, Thorpe SR. Identification of the sites of IgG catabolism in the rat. ― ― Arch Biochem Biophys.

1982; 215: 1-11. 参考

2.6.6-1

Shima DT, Gougos A,Miller JW, Tolentino M,Robinson G, Adamis AP,et al.

Cloning and mRNA expression of vascular endothelialgrowth factor in ischemic retinas of Macacafascicularis .

― ― Invest Ophthalmol VisSci. 1996; 37: 1334-1340. 参考

2.6.6-2 Ford EW, Roberts JA,Southers JL.

Chapter 8 Urogenital System. III Renal Disease. In:Nonhuman Primates in Biomedical Research:Diseases.

― ― Academic Press. 1998;315-319. 参考

2.6.6-3

Ryan AM, Eppler DB,Hagler KE, Bruner RH,Thomford PJ, Hall RL, etal.

Preclinical safety evaluation of rhuMAbVEGF, anantiangiogenic humanized monoclonal antibody. ― ― Toxicol Pathol. 1999; 27:

78-86. 参考

2.6.6-4

Howdieshell TR, RiegnerC, Gupta V, Callaway D,Grembowicz K,Sathyanarayana, et al.

Normoxic wound fluid contains high levels of vascularendothelial growth factor. ― ― Ann Surg. 1998; 228:

707-715. 参考


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2.6.6-5

Nissen NN, Polverini PJ,Koch AE, Volin MV,Gamelli RL, DiPietro LA,et al.

Vascular endothelial growth factor mediatesangiogenic activity during the proliferative phase ofwound healing.

― ― Am J Pathol. 1998; 152:1445-1452. 参考

2.6.6-6 Tonnesen MG, XiaodongF, Clark RAF. Angiogenesis in wound healing. ― ― J Investig Dermatol Symp

Proc. 2000; 5: 40-46. 参考

2.6.6-7Dobyan DC, Levi J,Jacobs C, Kosek J,Weiner MW.

Mechanism of cis-platinum nephrotoxicity: IIMorphologic observations. ― ― J Pharmacol Exp Ther.

1980; 213: 551-556. 参考

2.6.6-8 Kim YK, Byun HS, KimYH, Woo JS, Lee SH.

Effect of cisplatin on renal function in rabbits:Mechanism of reduced glucose reabsorption. ― ― Toxicol Appl Pharmacol.

1995; 130: 19-26. 参考

2.6.6-9 Dixon FJ, Feldman JD,Vazquez JJ.

Experimental glomerulonephritis. The pathogenesis ofa laboratory model resembling the spectrum of humanglomerulonephritis.

― ― J Exp Med. 1961; 113:899-937. 参考

2.6.6-10

Richards AB, KrakowkaS, Dexter LB, Schmid H,Wolterbeek APM,Waalkens-Berendsen DH,et al.

Trehalose: a review of properties, history of use andhuman tolerance, and results of multiple safety studies. ― ― Food Chem Toxicol.

2002; 40: 871-898. 参考

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2.6.6-11 Bär A. Trehalose produced by a novel enzymatic process. ― ―UK Advisory Committeeon Novel Foods andProcesses. 2000.

参考

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5.2 中外製薬株式会社臨床試験一覧表 ― ― 社内資料 ―

第5部（モジュール5）　臨床試験報告書　添付資料一覧5.2 臨床試験一覧表

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参考表題実施期間実施場所



該当資料なし

該当資料なし

該当資料なし

5.3.1.4-1 20 年～報告書作成日

（報告書20 年月日）

海外社内資料評価

5.3.1.4-2 19 年～報告書作成日

（報告書20 年月日）

海外社内資料参考

5.3.1.4-320 年月日

～20 年月日国内

社内資料参考

第5部（モジュール5）　臨床試験報告書　添付資料一覧

5.3.1 生物薬剤学的試験報告書

5.3.1.2 比較BA試験及び生物学的同等性（BE）試験報告書

5.3.1.3 In Vitro -In Vivoの関連を検討した試験報告書

5.3 試験報告書及び関連情報

5.3.1.4 生物学的及び理化学的分析法検討報告書

5.3.1.1 バイオアベイラビリティ（BA）試験報告書

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第5部（モジュール5）　臨床試験報告書　添付資料一覧5.3 試験報告書及び関連情報

該当資料なし

該当資料なし

該当資料なし

該当資料なし

5.3.3.2-1

AVF0737g: A phase I, open-label,multicenter, dose-escalation study of theinitial safety and pharmacokinetic profilesof recombinant humanized anti-VEGFmonoclonal antibody (rhuMAb VEGF) insubjects with advanced malignancies

1997年月

～19 年月海外社内資料評価

5.3.2 ヒト生体試料を用いた薬物動態関連の試験報告書

5.3.2.1 血漿蛋白結合試験報告書

5.3.2.2 肝代謝及び薬物相互作用試験報告書

5.3.2.3 他のヒト生体試料を用いた試験報告書

5.3.3 臨床薬物動態（PK）試験報告書

5.3.3.1 健康被験者におけるPK及び初期忍容性試験報告書

5.3.3.2 患者におけるPK及び初期忍容性試験報告書

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5.3.3.2-2

AVF0761g: A phase I, open-label,multicenter, dose-escalation study of thesafety and pharmacokinetics of multipledoses of recombinant humanizedmonoclonal anti-VEGF antibody(rhuMAb VEGF) in combination withchemotherapy in subjects with advancedsolid malignancies

1997年月


5.3.3.2-3JO18157：RO4876646（Bevacizumab）の進行 / 再発結腸・

直腸癌を対象とした第I/II相試験

2004年月～国内社内資料評価

5.3.3.2-4

JO18157：RO4876646（Bevacizumab）の進行 / 再発結腸・

直腸癌を対象とした第Ⅰ/Ⅱ相試験　統計解析報告書

（をcut off 日とした中間集

計）（分冊を除く）

2004年月～国内社内資料参考

5.3.3.2-5

JO18157：RO4876646（Bevacizumab）の進行 / 再発結腸・

直腸癌を対象とした第Ⅰ/Ⅱ相試験薬物動態解析報告書

（をcut off 日とした中間集

計）Ver.

2004年月～国内社内資料参考

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*新薬情報提供時に置き換えた

開始後35週時点

*最終症例投与

開始後35週時点

*最終症例投与






該当資料なし

該当資料なし

5.3.3.5-1 20 年月海外社内資料評価

該当資料なし

該当資料なし

5.3.3.5 ポピュレーションPK試験報告書

5.3.4 臨床薬力学（PD）試験報告書

5.3.4.1 健康被験者におけるPD試験及びPK/PD試験報告書

5.3.3.3 内因性要因を検討したPK試験報告書

5.3.3.4 外因性要因を検討したPK試験報告書

5.3.4.2 患者におけるPD試験及びPK/PD試験報告書

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5.3.5.1-1

AVF2107g: A Phase III, Multicenter,Randomized, Active-Controlled ClinicalTrial to Evaluate the Efficacy and Safetyof rhuMAb VEGF (Bevacizumab) inCombination with Standard Chemotherapyin Subjects with Metastatic ColorectalCancer

・2000年9月～Data Cutoffs: 2003年月

(all data except survival),2003年月 (survival data)

・Addendum　2000年9月～

2004年月


5.3.5.1-2

AVF2192g: A Phase II, Multicenter,Double-Blind, Randomized, Active-Controlled Clinical Trial to Evaluate theEfficacy and Safety of rhuMAb VEGF(Bevacizumab), A RecombinantHumanized Monoclonal Antibody toVascular Endothelial Growth Factor, inCombination with 5-Fluorouracil andLeucovorin Chemotherapy in Subjectswith Metastatic Colorectal Cancer Whoare not Optimal Candidates for First-LineCPT-11

・2000年8月～Data Cutoffs: 20 年月

(all data except survival)，20 年月 (survival data)

・Addendum　2000年8月～

20 年月


5.3.5 有効性及び安全性試験報告書

5.3.5.1 申請する適応症に関する比較対照試験報告書

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5.3.5.1-3

AVF0780g: A Phase II, Multidose,Randomized, Multicenter Clinical Trial toEvaluate the Efficacy, Safety, andPharmacokinetics of RecombinantHumanized Monoclonal Anti-VEGFAntibody (rhuMAb VEGF) combinedwith 5-Fluorouracil and LeucovorinChemotherapy in Subjects with MetastaticColorectal Cancer

1998年月


5.3.5.1-4

E3200: Phase III Trial of Bevacizumab(NSC704865), Oxaliplatin (NSC266046),Fluorouracil, and Leucovorin VersusOxaliplatin, Fluorouracil, and LeucovorinVersus Bevacizumab Alone in PreviouslyTreated Patients with AdvancedColorectal Cancer

2001年月

～2005年月海外社内資料参考

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5.3.5.1-5 ―

Study NO16966A 2x2 Factorial Randomized Phase IIIStudy of Intermittent Oral Capecitabine inCombination with Intravenous Oxaliplatin(Q3W) ("XELOX") with/withoutIntravenous Bevacizumab (Q3W) versusBolus and Continuous InfusionFluorouracil/ Intravenous Leucovorin withIntravenous Oxaliplatin (Q2W)("FOLFOX-4") with/without IntravenousBevacizumab (Q2W) as First-lineTreatment for Patients with MetastaticColorectal CancerSummary of key study results forRegulatory Authorities

2003年月～海外社内資料参考

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5.3.5.1-6

ARD-5099: A RANDOMIZED,PROSPECTIVE STUDY COMPARINGTHREE REGIMENS OFELOXATINTM PLUSFLUOROPYRIMIDINE (TREE1STUDY) WITH THE ADDITION OFAVASTINTM (TREE2 STUDY) OREVALUATION OF SAFETY ANDTOLERABILITY IN FIRST LINETREATMENT OF PATIENTS WITHADVANCED COLORECTAL CANCER

20 年月～20 年月海外社内資料参考

5.3.5.2-1

AVF2540g: An Open-Label, MulticenterExtension Study of rhuMAb VEGF(Bevacizumab) in Subjects Treated in aPrevious -Sponsored CancerStudy

20 年月

～20 年月海外社内資料参考

5.3.5.2 非対照試験報告書

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5.3.5.2-2

AVF0778g: An Open-Label, MulticenterExtension Study of RecombinantHumanized Monoclonal Anti-VEGFAntibody (rhuMAb VEGF, Bevacizumab)in Subjects Treated with rhuMAb VEGFin a Previous -Sponsored PhaseI or Phase II Cancer Study

19 年月

～20 年月海外社内資料参考

5.3.5.2-3

E2200: A Phase II Trial of Fluorouracil,Leucovorin, Irinotecan and Bevacizumab(Anti-VEGF) in Previously UntreatedPatients with Advanced Colorectal Cancer

2000年11月～20 年月

海外ECOG Technical

Report 参考

5.3.5.2-4

JO18158: RO4876646（Bevacizumab）の進行・再発結腸・直腸癌を対象とした安全性確認試験　統計解析報告書（2006/3/31をcut off 日とした中間

集計）（分冊を除く）

20 年月～国内社内資料参考

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5.3.5.3-1 Kabbinavar FF

Combined analysis of efficacy: theaddition of bevacizumab tofluorouracil/leucovorin improves survivalfor patients with metastatic colorectalcancer

― 海外J Clin Oncol. 2005; 23:

3706-3712. 参考

5.3.5.3-2 ― ― 海外

Roche社　社内資料

（

）

参考

5.3.5.3-3

AVF2107g, AVF2192g, AVF0780g,JO18157: Bevacizumab（RO4876646）海外及び国内臨床試験の安全性に関する統合解析

― 海外，国内社内資料参考

5.3.5.3 複数の試験成績を併せて解析した報告書

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5.3.5.4-1

AVF2119g: A Multicenter, Open-Label,Phase III, Randomized, Active-ControlledTrial Evaluating the Efficacy, Safety, andPharmacokinetics of rhuMAb VEGF(Bevacizumab), in Combination withCapecitabine Chemotherapy, in Subjectswith Previously Treated Metastatic BreastCancer

2000年月


5.3.5.4-2

AVF0757g: A Phase II, Multidose,Randomized, Multicenter Clinical Trial toEvaluate the Efficacy, Safety,Pharmacokinetics, and Pharmacodynamicsof Recombinant Humanized MonoclonalAnti-VEGF Antibody (rhuMAb VEGF)Combined with Carboplatin and PaclitaxelChemotherapy in Subjects with

Non-Small Cell Lung Cancer

1998年月


5.3.5.4 その他の臨床試験報告書

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5.3.5.4-3

AVF0776g: A Phase II, Open-Label,Multidose, Multicenter Study to Evaluatethe Safety, Efficacy, andPharmacokinetics of RecombinantHumanized Monoclonal Anti-VEGFAntibody (rhuMAb VEGF) asMonotherapy in Subjects with RelapsedMetastatic Breast Cancer

1998年月


5.3.5.4-4

AVF0775g: A Pilot Phase II, Open-Label,Multidose Study to Evaluate the Efficacy,Safety and　Pharmacokinetics ofRecombinant Humanized MonoclonalAnti-VEGF (rhuMAb VEGF) asMonotherapy in Subjects　withHormone-Refractory Prostate Cancer

1998年月


5.3.6-1 ― 　海外における重篤な有害事象一覧～2005年月日海外社内資料参考

5.3.6-2 ―Periodic safety update reportNo1019578

2004年月日

～2005年月日海外社内資料参考

5.3.6 市販後の使用経験に関する報告書

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5.3.7.1-1 ― AVF0737g試験：症例一覧・副作用症

例一覧表― 海外社内資料評価



5.3.7.1-3 ― JO18157試験：症例一覧・副作用症例

一覧表― 国内社内資料評価







5.3.7.1-7 ― E3200試験：症例一覧・副作用症例一

覧表― 海外社内資料参考

5.3.7.1 主要な試験の症例一覧表，副作用症例一覧表

5.3.7 患者データ一覧表及び症例記録

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5.3.7.2-1 ― AVF0737g試験：重篤な有害事象症例

一覧表― 海外社内資料評価



5.3.7.2-3 ― JO18157試験：重篤な有害事象症例一

覧表― 国内社内資料評価







5.3.7.3-1 ― AVF0737g試験：臨床検査値異常変動

症例一覧表― 海外社内資料評価

5.3.7.2 重篤な有害事象症例一覧表

5.3.7.3 臨床検査値異常変動症例一覧表

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5.3.7.3-3 ― JO18157試験：臨床検査値異常変動症

例一覧表― 国内社内資料評価







5.3.7.4-1 ― AVF2107g試験：臨床検査値変動図 ― 海外社内資料評価

5.3.7.4-2 ― AVF2192g試験：臨床検査値変動図 ― 海外社内資料評価

5.3.7.4-3 ― JO18157試験：臨床検査値変動図 ― 国内社内資料評価

5.3.7.4 臨床検査値変動図

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5.4.1-1 ― 医薬品第I相試験開始前相談　治験相談記録

― ― 薬機審長発第号，平成年月日参考

5.4.1-2 ― 医薬品申請前相談議事録 ― ― 薬機審長発第号，平成年

月日参考

5.4.1-3 ― 医薬品追加相談議事録 ― ― 薬機審長発第号，平成年

月日参考

2.5-1 ― がんの統計’05 ― ― (http://www.ncc.go.jp/jp/statistics/2005/index.html) 参考

2.5-2 Meyerhardt JA, MayerRJ. Systemic therapy for colorectal cancer. ― ― N Engl J Med. 2005; 352: 476-487. 参考

2.5-3 ―

National Comprehensive Cancer Network(NCCN): Clinical practice guideline inOncology v2.2006; Colon Cancer, RectalCancer

― ―

(http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf)(http://www.nccn.org/professionals/physician_gls/PDF/rectal.pdf)

参考

第5部（モジュール5）　臨床試験報告書　添付資料一覧5.4 参考文献

5.4.1 治験相談記録

5.4.2 参考文献一覧

2.5の参考文献

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2.5-4 ―

National Cancer Institute: PDQ®(Physician Data Query)- NCI'sComprehensive Cancer Database: PDQ®-Cancer Information Summaries: AdultTreatment (Health Professional Version):Colon Cancer, Rectal Cancer

― ―

(http://www.cancer.gov/cancertopics/pdq/treatment/colon/healthprofessional/)(http://www.cancer.gov/cancertopics/pdq/treatment/rectal/healthprofessional/)

参考

2.5-5 ― 大腸癌研究会編：大腸癌治療ガイドライン医師用2005年版

― ― 金原出版; 2005. 参考

2.5-6 Folkman J. Tumor angiogenesis: therapeuticimplications. ― ― N Engl J Med. 1971; 285: 1182-1186. 参考

2.5-7 Ferrara N. VEGF and the quest for tumourangiogenesis factors. ― ― Nat Rev Cancer. 2002; 2: 795-803. 参考

2.5-8 Ferrara N, Gerber HP,Le Couter J. The biology of VEGF and its receptors. ― ― Nature Medicine. 2003; 9: 669-676. 参考

2.5-9 Bergers G, BenjaminLE. Tumorigenesis and the angiogenic switch. ― ― Nature Rev. 2003; 3: 401-410. 参考

2.5-10 Ferrara N, Davis-Smyth T.

The biology of vascular endothelialgrowth factor. ― ― Endocr Rev. 1997; 18: 4-25. 参考

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2.5-11Takahashi Y, KitadaiY, Bucana CD, ClearyKR, Ellis LM.

Expression of vascular endothelial growthfactor and its receptor, KDR, correlateswith vascularity, metastasis, andproliferation of human colon cancer.

― ― Cancer Res. 1995; 55: 3964-3968. 参考

2.5-12 Takahashi Y, TuckerSL, Kitadai Y, et al.

Vessel counts and expression of vascularendothelial growth factor as prognosticfactors in node-negative colon cancer.

― ― Arch Surg. 1997; 132: 541-546. 参考

2.5-13Takahashi Y, BucanaCD, Cleary KR, EllisLM.

p53, vessel count, and vascular endothelialgrowth factor expression in human coloncancer.

― ― Int J Cancer. 1998; 79: 34-38. 参考

2.5-14Warren RS, Yuan H,Matli MR, Gillett NA,Ferrara N.

Regulation by vascular endothelial growthfactor of human colon cancertumorigenesis in a mouse model ofexperimental liver metastasis.

― ― J Clin Invest. 1995; 95: 1789-1797. 参考

2.5-15 Radinsky R, Ellis LM. Molecular determinants in the biology ofliver metastasis. ― ― Surg Oncol Clin N Am. 1996; 5: 215-

229. 参考

2.5-16

Tokunaga T, Oshika Y,Abe Y, Ozeki Y,Sadahiro S, Kijima H,et al.

Vascular endothelial growth factor(VEGF) mRNA isoform expressionpattern is correlated with liver metastasisand poor prognosis in colon cancer.

― ― Br J Cancer. 1998; 77: 998-1002. 参考

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2.5-17Borgstrom P, HillanKJ, Sriramarao P,Ferrara N.

Complete inhibition of angiogenesis andgrowth of microtumours by anti-vascularendothelial growth factor neutralizingantibody: novel concepts of angiostatictherapy from intravital videomicroscopy.

― ― Cancer Res. 1996; 56: 4032-4039. 参考

2.5-18

Hurwitz H,Fehrenbacher L,Novotny W, CartwrightT, Hainsworth J, HeimW, et al.

Bevacizumab plus irinotecan, fluorouracil,and leucovorin for metastatic colorectalcancer.

― ― N Engl J Med. 2004; 350: 2335-2342. 参考

2.5-19

Kabbinavar FF, SchulzJ, McCleod M, Patel T,Hamm JT, Hecht R, etal.

Addition of bevacizumab to bolusfluorouracil and leucovorin in first-linemetastatic colorectal cancer: Results of arandomized phase II trial.

― ― J Clin Oncol. 2005; 23: 3697-3705. 参考

2.5-20

Kabbinavar F, HurwitzH, Fehrenbacher L,Meropol NJ, NovotnyWF, Lieberman G, etal.

Phase II, randomized trial comparingbevacizumab plus fluorouracil(FU)/Leucovorin (LV) with FU/LV alonein patients with metastatic colorectalcancer.

― ― J Clin Oncol. 2003; 21: 60-65. 参考

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2.5-21

Kabbinavar FF,Hambleton J, MassRD, Hurwitz H,Bergsland E, Sarkar S.

Combined analysis of efficacy: theaddition of bevacizumab tofluorouracil/leucovorin improves survivalfor patients with metastatic colorectalcancer.

― ― J Clin Oncol. 2005; 23: 3706-3712. 参考

2.5-22

Saltz LB, Cox JV,Blanke C, Rosen LS,Fehrenbacher L, MooreMJ, et al.

Irinotecan plus fluorouracil and leucovorinfor metastatic colorectal cancer. ― ― N Engl J Med. 2000; 343: 905–914. 参考

2.5-23 Lee AYY, Levine MN. Venous thromboembolism and cancer:risks and outcomes. ― ― Circulation. 2003; 107: I-17-21. 参考

2.5-24Hoff PM, Ansari R,Batist G, Cox J, KochaW, Kuperminc M, et al.

Comparison of oral capecitabine versusintravenous fluorouracil plus leucovorin asfirst-line treatment in 605 patients withmetastatic colorectal cancer: results of arandomized phase III study.

― ― J Clin Oncol. 2001; 19: 2282-2292. 参考

2.5-25

Twelves C, Boyer M,Findlay M, Cassidy J,Weitzel C, Barker C, etal;

Xeloda Colorectal Cancer Group.Capecitabine (Xeloda) improves medicalresource use compared with 5-fluorouracilplus leucovorin in a phase III trialconducted in patients with advancedcolorectal carcinoma.

― ― Eur J Cancer. 2001; 37: 597-604. 参考

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2.5-26

Giantonio BJ, LevyDE, O’Dwyer PJ,Meropol NJ, CatalanoPJ, Benson AB 3rd

A phase II study of high-dosebevacizumab in combination withirinotecan, 5-fluorouracil, leucovorin, asinitial therapy for advanced colorectalcancer: results from the easterncooperative oncology group study E2200.

― ― Ann Oncol 2006; 17: 1399-403, Epub2006 Jul 27. 参考

2.5-27

Hochster HS, Hart LL,Ramanathan RK,Hainsworth JD,Hedrick EE, ChildsBH, et al.

Safety and efficacy ofoxaliplatin/fluoropyrimidine regimen withor without bevacizumab as first-linetreatment of metastatic colorectal cancer(mCRC): final analysis of the TREE-2study.

― ― J Clin Oncol 2006; 24: abstract 3510. 参考

2.5-28

Kozloff M, HainsworthJ, Badarinath S, CohnA, Flynn P, Steis R,etal.

Efficacy of bevacizumab pluschemotherapy as first-line treatment ofpatients with metastatic colorectal cancer:updata results from a large observationalregistry in the US (BRiTE).


2.5-29

Sobrero A, Ackland S,Carrion RP, Chiara S,Clarke S, Giron CG, etal.

Efficacy and safety of bevacizumab incombination with irinotecan and infusional5-FU as first-line treatment for patientswith metastatic colorectal cancer.


2.5-30

Fuchs C, Marshall J,Mitchell E, WierzbickiR, Ganju V, Jeffery M,et al.

A randomized trial of first-lineirinotecan/fluoropymidine combinationswith or without celecoxib in metastaticcolorectal cancer (BICC-C).

― ― J Clin Oncol 2006;24(June 20 Suppl.):147s (abstract 3506). 参考

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2.7.3-2

Sandler AB, Gray R,Brahmer J, Dowlati A,Schiller JH, Perry MC,et al.

Randomized phase II/III Trial of paclitaxel(P) plus carboplatin (C) with or withoutbevacizumab (NSC # 704865) in patientswith advanced non-squamous non-smallcell lung cancer (NSCLC): An EasternCooperative Oncology Group (ECOG)Trial - E4599. 2005 ASCO AnnualMeeting Abstract No:4

― ―

http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_detail_view&confID=34&abstractID=33325

参考

2.7.3-3

Miller K, Wang M,Gralow J, Dickler M,Cobleigh MA, PerezEA et al.

First-line bevacizumab and paclitaxel inpatients with locally recurrent ormetastatic breast cancer: a randomized,phase III trial coordinated by the EasternCooperative Oncology Group (E2100).ECCO 13 – the European CancerConference (2005) Abstract 275

― ―

http://ex2.excerptamedica.com/ciw-05ecco/index.cfm?fuseaction=CIS2002&hoofdnav=Abstracts&content=abs.details&what=FREE%20TEXT&searchtext=e2100&topicselected=*&selection=ABSTRACT&qryStartRowDetail=1

参考

2.7.3-4

Yang JC, Haworth L,Sherry RM, Hwu P,Schwartzentruber DJ,Topalian SL, et al.

A Randomized Trial of Bevacizumab, anAnti-Vascular Endothelial Growth FactorAntibody, for Metastatic Renal Cancer.

― ― New Engl J Med. 2003; 349: 427-434. 参考


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2.7.4-2

Rothenberg ML,Meropol NJ, PoplinEA, Cutsem EV,Wadler S

Mortality Associated With Irinotecan PlusBolus Fluorouracil/Leucovorin: SummaryFindings of an Independent Panel

― ― J Clin Oncol. 2001; 19: 3801-3807 参考

2.7.4-3Glusker P, Recht L,Lane B, Ozcan C,Wong SJ, Hari P, et al.

Reversible Posterior LeukoencephalopathySyndrome and Bevacizumab ― ― New Engl J Med. 2006; 354: 980-981. 参考


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4.2.3.7.3　毒性発現の機序に関する試験

4.2.3.5.1　受胎能及び着床までの初期胚発生に関する試験

4.2.3.5.3　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

4.2.3.5.4　新生児を用いた試験

4.2.3.6　局所刺激性試験

4.2.3.7.1　抗原性試験

4.2.3.7.2　免疫毒性試験

提出すべき資料がない項目リスト

4.2.1.3　安全性薬理試験

4.2.1.2　副次的薬理試験

第3部（モジュール3）　品質に関する文書

3.2.R　各極の要求資料

第4部（モジュール4）　非臨床試験報告書

4.2.3.1　単回投与毒性試験

4.2.3.3.1　In Vitro試験

4.2.3.3.2　In Vivo試験

4.2.3.4　がん原性試験

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5.3.1.1　バイオアベイラビリティ（BA）試験報告書

5.3.1.2　比較BA試験及び生物学的同等性（BE）試験報告書

5.3.1.3　In Vitro -In Vivoの関連を検討した試験報告書

4.2.3.7.4　依存性試験

4.2.3.7.5　代謝物の毒性試験

第5部（モジュール5）　臨床試験報告書

4.2.3.7.6　不純物の毒性試験

5.3.4.2　患者におけるPD試験及びPK/PD試験報告書

5.3.2.1　血漿蛋白結合試験報告書

5.3.2.2　肝代謝及び薬物相互作用試験報告書

5.3.2.3　他のヒト生体試料を用いた試験報告書

5.3.3.3　内因性要因を検討したPK試験報告書

5.3.3.4　外因性要因を検討したPK試験報告書

5.3.4.1　健康被験者におけるPD試験及びPK/PD試験報告書

5.3.3.1　健康被験者におけるPK及び初期忍容性試験報告書

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Documents

第4部（モジュール4） 非臨床試験報告書 添付資料一覧 4.3 参考 … · Cloning and mRNA expression of vascular endothelial growth factor in ischemic retinas of

第4部（モジュール4）非臨床試験報告書添付資料一覧 4.3 参考 … · Cloning and mRNA expression of vascular endothelial growth factor in ischemic retinas of