I76 Abstracts

118 120

A PHASE II TRIAL WITH D-T~D-~ (DECAPEPTYL) IN PREMENOPAUSAL RHt, HORMONAL'UNTREATEO ADVANCED BREAST CANCER PATIENTS. E.Garcia-Giralt, P.Beuzaboc, T.Dorval, M.Jouve, A.Livartowski, T.Palangia,S.Scholl,P.Pouillart. Institut Curie, Opt MBdecine Oncologiqua. Paris, France. LHRH analoguas are suitable first-line agents for the treatment of pramenopausal breast can- car patients because their efficacy is compara- ble with that of surgical castration and becau- se they lack serious side affects. D-Trp-6 is a analogue of LHRH which inhibits breast cancer cell growth by several direct and indirect mecha- nisms. In a trial including 20 patients treated with S.C. injection of 3.75mg (each 28th day) of 6-Trp-6 for 3 to 35 months, no important side effects occured with the exception of those caused by the intended hypogonadism, expecially hot flushes. A few patients had more or lass short-term urticarial skin irritation with did not cause pain or disconfort. Of 19 evaluabla patients there were 4 CR (9, 20, 23, and 35 months), B PR, 1 stable disease and 6 patients progressed. We concluded that D-Trp-6 is a non toxic and clinically active inhibitor of breast tumor proliferation in pramenopausal RH + selected patients.

119

Gn-RH AWALOGUE SOSERELIN (ZOLADEX) Ill THE TREATMENT OF PRE-AID

PERIYENOPAUSAL WONEN WITH YETASTATIC BREAST CANCER RESULTS OF A WLTICENTRIC STUDY.

A.R.Bltnco(l). S. Da Pl,cIdo(l), F.Cal,brcsl(Z), Y.Fl,rtntIno(S),

Y. For,tr(r), R. L,nt I (5), R. Ror,o(b), P. 6. Slraondl(l),

R. Artloll( ITALY.

1)Dlvirlon of Y,dlcrl Oncolo6y,tJ”iv,rrlty of tt1pl,1 Y,dlcal

School II; Z)Dlvlrlo” of Y,dlc,l O”Colo6y, TuDUf ln‘tltut,,

R,gln, Eltna. Ron,; 3)Dlvlrlo” of Y,dlr‘l O”tolo;y, S,“tr,l

Ho‘plttl of Padul; 4)0lvl,lun of Y,dlcal Oncolo#y, 6,“,fal

Horplt~l Of Ylonz, ; 5)Divl‘lon of Nutl,,r Y,dlrl”, ,“d

Oncolo6y. Gtn,rrl Ho‘plt‘l Of Ttr,mo; 6)Dlvl‘lo” of Ytdlcrl

DneoloRy, Tumour In,tltut,. 6tno1; 7)Dlvl,lon of Ob,t,trIc, ,“d

6yn~troloSy,U”lv,r,lty 01 Turin; 6)ICI Pbwm,; ITALY.

Slrty-four prc-p,rlmtnopw,tl patltnt, with m,ta,t,tIc brvait

,,nc,r (m*,n ,R, 42 y,,r,, renp, 26.56) wr, ‘ub),ct,d to

‘Zul,d,x’, a l,“R act Ing GnRH-,“,lo:uc d,pot pr,p,r8t IO”,

lnjactvd ‘.c.,vvry Z6 day‘. 53 patI,“tr .,r, ,wlutbl,, Of wbua

24 htd rcolvtd ,djuv,nt cytotoxlt cb,motb,rapy, 2 ,dluv,“t

bormonotb,rapy tnd 27 no prwlou, tr,,tm,nt. Domlntnt ‘It, of

m,twt,‘,r WI‘ raft-tlr‘uc(loco-r,Rlonal) In 14, bon, In 16 and

*I,cvral I” 23. Svrum o,stradloI. LH md FM “,r, supprtr‘,d by ‘Zol‘dvx’. Y,an owtrvdlol value, f,II Into thv ,,“R, Of

ctrtr,tlon VIIU, wlthln 4 w,,L of thtrapy and tbl, ‘uppr,‘rlun

wv, m,inttin,d throughout th,r,py. 16/53 (30.2%) patI,nt, thovmd

,I ,bJvctiv, rvtp,“‘.: 5(9.4X) I complvt, rvrpo”,, and ll(tO.71) a p,rt1,1 rvrponr,. Y,dlr” durltlon of rap,“‘, vf.‘ 36 w,,b‘

(rang, 16.76). Sit, of r,,p,n,, “a, loco.r,Rlo”,l In 64%. bon, In

1’2% ,“d ll‘c,ra In 22%. Objtctlv, r,‘pon‘, arrordl”6 to

ITI,DO~,U,II status iv“ obtrln,d In 15/46(32.6%) I” prw,“opau‘rl

,“d l/7(14.3%) I” p,rIn,nopwJs,I pltltnt,. Zoltdtr WI,

rdmlnl,ttr,d ,,,lIy ,. c. ctrh month and w,, wll tolvrattd

WItbout ,,rlou: to,iclty. No patl,“t w‘, wltbdrtm due to a”

adwr,, ratctlon.

GROYTH INHIBITORY EFFECT OF SOHdTOSTllTlN AN106 (RC-160) IN HCF-7 CELLS. M.A. Llorens, A,L. Charro and H. Puente. Hospital Univcrsitario San Carlos, Scrvirio de Endocrinologia, ffetabolisro y Nutriribn, Madrid, Spain, Various horeoncs and grovth factors have been implicated in the grorth regulation of huaan breast tanrer. Breast cancer cells have been shorn to produte 16F-I and E6F polipeptides rith confirmed nitogenlr activity and autotrine grorth fatlor properties, Somatostatin and its analogs either directly or indirectly through suppresion of grorth hormone, can inhibit the action of these growth factors, To ronfirs the direct paracrine or autocrine inhibitory actions of sosatostalin in cell proiaferalion ve have studied a ner soectostatin rnalog (RC-160) for the ability to inhibit the growth of HCF-7 cells, Cells (5.10*) were either cultured in 21-sells clusters in nediue supplemented vith 10X inactivated and steroid depleted fetal calf serus or in 10X fetal calf sew that had been inactivated for 30 sin, at 66% (rorplete grorth rdius, C6M. Cells sere plated at densities indicated above and the folloring day sonatostatin analog (O.Olnfl to Iptl) or control vehicle serc added to the sells, One, three and five days later cells were harvested and counted in an heeatocyter. DNA tontent of the cells vas estieated by a fluorieetric lethod, Proliferation of cell cultures in C6If eediue vas significantly inhibited (10X- 706) a1 IOnfl concentration of RC-160. ON11 content of cell cultures shoved growth decreases at various sosatostatin analog concentrations and aaxisal decrease (601) uas again observed at IOnN of K-160. Growth inhibition vas less pronunted rhen steroid depleted serue was used in the erdiue, In this case saxieal decrease (50X of controls) in rell nusber have been obtained at concentrations of soeatostatin analog IOnff Sirilar results were obtained rhen DNA content of cells was analyzed. Ye conclude that sosatostatin analog (RC-160) has a dirert inhibitory effect on proliferation of ffCF-7 ceils.

121

THE ENDOCRINE EFFECTS OF BROMOCRIPTINE AND SMS 201-995 IN ADVANCED BREAST CANCER PATIENTS E Anderson, H Morten, 1.l Ferguson, 2SM Shalet, 3L Robinson and 1A Howell, De t's of Clinical Research, IMedical Oncology, $ Endocrinology b 3Chemical Pathology, Christie & Withington Hospitals, Manchester, UK. Six patients who had failed first and second line endocrine therapies received bromocript- ine (2.5mg bd, po) and SMS 201-995 via a continuous subcutaneous infusion (200 or 4OOug/ 24h) until disease pronression. At the start of treatment 24h profiles of serum lactogenic hormones were established. These profiles were repeated at 2 wks, 3mths and 6mths (or at tumour progression) after the start of treat- ment. lmmunoreactive prolactin and growth hormone (ir-PRL and ir-GH) were measured by RIA, bioactive lactogen (EL) was estimated using the Nb2 rat lymphoma cell bioassay. Before treatment all pts showed episodic sec- retion of ir-PRL, ir-GH and BL. After 2 weeks of treatment, ir-PRL was reduced to below the limit of detection, peaks of ir-GH were still fE;;;znt and correlated well with the BL

. In one patient who was profiled at 3 and 6 months after the start of treatment, ir-PRL remained suppressed and episodic secre- tion of ir-GH and BL was still evident. Of the six pts treated, two showed stabilisation of their disease. These results indicate that ir-PRL can be effectively suppressed in advanced breast cancer patients but SMS 201- 995 at the doses used does not completely abolish ir-GH secretion.