Gastric Cancer Effectively Treated by Neoadjuvant Continuous Low-dosage 5-fluorouracil and Cisplatin (FP Regimen): A Case Report

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1 Cse Report Kurume Medicl Journl, 48, , 2001 Advnced Gstric Cncer Effectively Treted Neodjuvnt Ctuous Low-dosge 5-fluorourcil Cisplt (FP Regimen): A Cse Report KEISHIRO AOYAGI, KIKUO KOUFUJI, SHOJIRO YANO, NAOTAKA MURAKAMI, MOTOSHI MIYAGI, JINRYO TAKEDA AND KAZUO SHIROUZU Deprtment Surgery, Kurume University School Medice, Kurume , Jpn Summry: We hve experienced cse dvnced cncer pr-ortic node metstsis effectively treted neodjuvnt ctuous low dosge 5-fluorourcil cisplt (FP regimen). ptient 67-yer-old mn dignosed s hvg dvnced cncer type 4 pr-ortic node metstsis. This ptient treted ctuous fusi 5- fluorourcil () 500 mg/dy, for 28 dys, fusi Cisplt 10 mg/dy over 1 hr dys 1-5, 8-12, 15-19, At 4 weeks lter, CT reveled tht swellg pr-ortic node hd disppered, thickeng smch wll hd dimished. This ptient underwent curtive operti, both serum level crcoembryl ntigen (CEA) crbohydrte ntigen (CA 19-9) decresed norml. se results suggested tht FP regimen n effective neodjuvnt tretment for dvnced cncer pr-ortic node metstsis. Key words dvnced cncer, neodjuvnt, FP regimen INTRODUCTION 5-fluorourcil () its derivtives hve commly been used tret gstrotestl brest denocrcom. is n ntimetbolite tht is time-dependent, its mjor cyxicity occurrg durg S phse. Tsujk et l. [1] reported tht rte hibiti thymidylte synthse (TS), n ttrctive trget cncer tissues, significntly higher group treted ctuous fusi thn group treted bolus jecti. Or studies hve shown tht 5- FU more effective when dmistered ctuous fusi thn when bolus jecti [2]. combti cisplt (FP) hs been shown hve synergistic effects gst denocrcom both bsic clicl vestigtis [3-6]. Shirsk et l. [3] reported tht, rodent tumor models, cisplt enhnced cyxicity hibitg trcellulr L-methie metbolism, csequently cresg reduced folte pool. Chung et l. [5] reported respse rte 50% FP regimen ptients crcom. Sski et l. [6] reported n overll respse rte 57.8% FP ptients col, smch, pncretic denocrcom. Moreover, FP regimen well lerted most ptients frequent nuse, vomittg, hemlogicl xicity [5,6]. In this rticle, we report cse dvnced cncer pr-ortic node metstsis effectively treted neodjuvnt ctuous lowdosge cisplt (FP regimen). CASE REPORT A 67-yer-old mn visited privte hospitl becuse discomfort bdomen fter etg, November Advnced cncer dignosed bsed gstrogrphy endoscopy. ptient referred Kurume University Received for publicti June 19, 2001

2 326 AOYAGI FT AL. Hospitl for furr exmti tretment for dvnced cncer December 20, On dmissi, liver, spleen tumor not plpble physicl exmti. serum level crcoembryl ntigen (CEA) elevted t 65.1 ng/ml 1), tht crbohydrte ntigen (CA19-9) elevted t ng/ml 2). Gstrogrphy gstrotestl endoscopic exmti showed cncer type 4, whole circle fornix (Figs 3 4). Computed mogrphy (CT) showed swellg pr-ortic lympy node thickeng smch wll 5). Neodjuvnt tretment ctuous low-dosge cisplt begun from December 25., t dosge 500 mg per dy, dmistered for 28 dys ctuous Chnges serum level CEA Before recognized fornix tretment, type 4 whole circle cncer gstrogrphy. fter tretment. 4. fter 2. Chnges serum level CA 19-9 tretment. Before wll whole circle endoscopy. Kurume Medicl Journl tretment, eng Vol. 48, No. 4, 2001 stiffness recognized thick fornix

3 TREATED BY NEOADJUVANT trvenous fusi. Cisplt (10 mg per dy) diluted 100 ml sle fused trvenously over 1 hr dys 1-5, 8-12, 15-19, After chemorpy, gstrogrphy gstrotestl endoscopic exmti showed thickeng stiffness smch wll reduced 6), depressed cncer lesi esophgel vsi swellg pered, decresed t 0 through Februry left 13, tht thrombocyte hd CA count 2, count Surgery 19-9 side-effect leukocyte 89,000/ƒÊ ptient thorco-bdoml wll grde tl (PS) disp- CEA leukopeni, 1. tretment ). tht hd level sttus showed smch 1), ng/ml performnce durg 47.7 CT node serum grde 2600/,ƒÊ1, 1. been chemorpy A ng/ml t thrombocypeni, 7). 8). 3.0 decresed pr-ortic thickeng dimished 327 FP REGIMEN hd performed lpromy primry tumor tretment, depressed loclized 5. Before tretment, swellg prortic (rrow) thickeng smch wll CT. 7. After recognized, smch pered After tretment, tumor ortic hd disp- Kurume Medicl Journl thickeng Vol. 48, No. 4, 2001 tretment, g smch gstrogrphy. wll improved 8. After 6. but regi stiffness endoscopy. swellg hd disppered, wll hd dimished pr thicken CT.

4 AOYAGI 328 No. but wll 1 perinel node 2 smch, liver metstsis methods gstrecmy, lower depressed lesi curvture fdgs n mucous chnge tubulr out cncer 9). mucosl superficil cells lesser hislogicl lyer, submu- modertely lyer resected submucosl denocrcom rec- size lyers, shped cm fibrosis subserosl entited irregulr showed D3 method fdgs 4.2 ~0.8 tl mcroscopic specimen bsent. esohgus ĕ-roux-en-y swellg recognized, pncreco-splenecmy, dissecti, structi. ly No. operti cosl differloclized 10). No mets- ET AL. tsis recognized pthologiclly. fl dignosis cncer type 0 llc, HO, PO, NO, TI StgeIA. refore, this operti ccluded hve been fully curtive operti (Curtive A). serum level CEA decresed t less thn 1.0 ng/ml 1), tht CA19-9 decresed t 18.7 ng/ml 2) April 19. However, serum level CEA cresed t 28.9 ng/ml 1), tht CA 19-9 cresed t ng/ml 2) June 3. Admistrti (250 mg/dy div), refore, begun from June 10. But, serum level CEA cresed t 66.4 ng/ml 1), tht CA19-9 cresed t ng/ml 2) July 30. A CT showed perinitis scites due recurrence cncer perineum August 1. At 8 mths fter rpy, ptient eventully died crcoms perinitis August 14, DISCUSSION prognosis swellg resected mcroscopic specimen ficil depressed lesser curvture n lesi fdgs irregulr 4.2 ~0.8 shped cm present tht dent thymidylte 16 (rrows). gicl or out cncer lyer, cells denocrcom lyer (H showed chnge submucosl loclized fibro- ly hrs tht superior tretment superior ntitumor tht bolus number low respse hs been cludg Or gent reported cluded rtes mucosl MTX E ~20). Kurunne Medicl Jom-nl cisplt compred more severl chemorpies ctivity for resulted Sce cisplt gst chemorpies [16], hve leucovor Vol. 48, No. 4, 2001 shown tht superior previous [17], lso denocrcom [11-13]. hve severl hve 20-30% hve tretment denocrcom rte led uthors 48 hrs). my sgle 48 effect fusi for fusi which mg/m2 mg/m2 ~2 cncer, [1]. tumor, (1000 ctuous effect dmistrti (500 sur- ntimetbolic cncers, A regil fter underwent specimens ctuous thn who jecti denocrcom, tubulr study hve subserosl modertely-differentited & fdgs romized hibiti fusi dvnced mucous 12 reported [2,7-9]. lyer, t provided dvnced hislogicl surgicl mucos, bolus effective treted rpy. schedule-depen- (TS) cncer ctuous reported submucosl If resecti We FP vestigte obted y 10. performed hrs) [1] curtive neodjuvnt synthse resecti, eir l. poor. is recognized successfully. cducted ptients chieve cse et norml sis pr-ortic very super- size been exmti, difficult Tsujk 9. cncer hs pr-ortic preopertive be metstsis my node respse regimen [14,15]. cisplt [18-21]

5 TREATED BY NEOADJUVANT FP REGIMEN 329 modulte ntitumor effect. Severl experimentl studies hve reveled synergism between cisplt vitro vivo [3,4]. Ctuous fusi cisplt fusi ppers be promisg combti. respse rte n FP regimen 50%, which significntly superior or two-drug combti chemorpies excludg cisplt similr or superior multiple drug combtis [5]. medin survivl ptients FP regimen 7.3 mths, which similr or superior survivl ptients given or two-drug combtis ( mths) [22,23]. high respse rte FP regimen my be expled not ly modulti phrmcologicl effect 5- FU cisplt but lso direct ntitumor effect cisplt [5]. In most combtis cisplt, cisplt is given bolus jecti ce per week or course. In our regimen, cisplt given dily for 5 dys ech week, for tl dosge bout 200 mg per course. Severl uthors reported tht ntitumor ctivity cisplt substntilly higher ptients given ctuous fusi cisplt thn fter similr dosge given s bolus [24,25]. Sski et l. [6] performed ctuous trvenous fusi t dosge 320 mg/m2/dy for 4 weeks, plus dily low-dosge cisplt between mg/m2/dy, fused for e hour five times week for 4 weeks, respse rte colorectl cncer cses 57.7%, pncres cncer 40%, cncer 62.5%, lung cncer 66.7%. Moreover, no severe side-effect occurred ny se cses. y reported tht this combti dily low-dosge cisplt chemorpy effective tretment dvnced gstrotestl lung denocrcom [6]. Ctuous fusi hs resulted lesser xcities higher respse rte thn bolus [9]. Moreover, ctuous or prolged cisplt fusi hs shown lower degree xicities ccompnied t lest sme level efficcy s bolus schedule [26,27]. Chung et l. [5] reported tht study FP regimen, ptients better PS (0 or 1) differentited hislogicl type showed higher respse rte thn did ptients poor PS (2 or 3) or undifferentited hislogicl type. From our cse, we decided tht curtive operti ctrdicted, becuse swellg pr-ortic node. However, fter FP regimen performed, we ble perform curtive resecti. A side-effect our cse ly slight leukopeni, grde 2. PS ptient hd been O durg tretment. refore, FP regimen csidered be useful neodjuvnt tretment for dvnced cncer pr-ortic node metstsis. REFERENCES 1. Tsujk T, Kido Y, Shiozki H, Iijim S, Homm T et l. Schedule-dependent hibiti thymidylte synthse 5-fluorourcil cncer. Cncer 1992; 70: Lokich JJ, Ahlgren JD, Gullo JJ, Phillips JA, Fryer JG. A prospective romized compris ctuous fusi fluorourcil cventil bolus schedule metsttic colorectl crcom: mid-tlntic cology progrm study. J Cl Oncol 1989; Shirsk T, Shimmo Y, Ohshim H, Si H, Fukushim M. Metbolic bsis synergistic ntitumor models vivo. Cncer Chemor Phrmcol 1993; 32: Scnl KJ, Newmn EM, Lu Y, Priest DG. Biochemicl bsis for cisplt 5-fluorourcil synergism humn ovrin crcom cells. Proc Ntl Acd Sci USA 1986; 83: Chung YS, Ymshit Y, Inoue T, Mtsuok T, Nkt B et l. Ctuous fusi 5-fluorourcil low dose cisplt fusi for tretment dvnced recurrent denocrcom. Cncer 1997; 80: Sski K, Hirt K, Denno R, Oikw I, Mukiy M et l. Combti chemorpy ctuous fusi 5- fluorourcil dily low-dose cisplt dvnced gstrotestl lung denocrcom. Jpn J Cncer Chemor (Gnn Kgkuryoho) 1997; 24: ( Jpnese) 7. Moynihn T, Hnsen R, Anders T, Quebbemn E, Betty P et l. Ctuous 5-fluorourcil fusi dvnced crcom. Am J Cl Oncol 1988; 11: Kish JA, Ensley JF, Jcobs J, Wever A, Cummgs G et l. A romized tril cisplt+ fusi cisplt+ bolus for recurrent dvnced squmous cell crcom hed neck. Cncer 1985; 56: Richrd MH, Louise R, Tom A, Beth K, Edwrd Q et l. Phse III study bolus versus fusi fluorourcil or out cisplt dvnced colorectl cncer. J Ntl Cncer Inst 1996; 88: Crter SK. Integrti chemorpy combed modlity tretment solid tumors. Cncer Tret Rev 1974;1: Mcdld J, Cohn I, Gunders L. Cncer smch. In: Cncer: prciples prctice cology. ed. De Vit V Jr., Hellmn S Rosenberg S, JB Lippcott, Phildelphi, pp , Lcve AJ, Izrzugz I, Ann-Apricio LM, Vlle- Perede MV, Grci-Mrco JM et l. Phse II clicl tril cisdichlorodimmepltum cncer. Am J Cl Oncol 1983; 6:5-8. Kurume Medicl Journl Vol. 48, No. 4, 2001

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