etoposide dosage in extensive stage small-cell lung cancer (SCLC)

61

cyclophosphamidc

600 mgfm’, cloposldc

100 mg/mzall

day 1-3, cbcry 3 weeks) m a randomlscd ucatcd wllh CVM

achxvcd

dcncc

hmlls

(88%)

(95% CL 80.97%.

13/17 (83%)

slgnifican1).

(67%)

(95% conti-

44/SO ucatcd

(95% CL 64100%)

(Y5W CL 8l-100%)

for CVM

dose rcduclionldclay

than ACE and conscqucntly

SuhJCLUvc roxuly

less for CVM rcgm~~

Pharmacokinetics

of bronchial

wuh

forCVM

was significantly

lower

and mfcc-

was low and alopccla wac

than ACE. CVM

new chcmothcrapy

ACE

ucaicd

median survival was 8 months toxiuy

slgnificanlly

with

had an objcctlvc

and 7 months for ACE. Hacmatologlcal lion wcrc ICS with CVM.

patients

For patients wllh hmltcd dlscasc

14/15 (Y3%)

Overall

rcsponsc witi

P = 0.06).

rcsponsc compared wllh ACE(no1

an ObJccllvc

(CL1 54.79%~) cornpa&

mcatcd wnlh CVM,

intmvcnously

trial. 36/54 cvaluable

IS an act~vc, well tolcratcd

Circumvention human ICI

patients

with

non-small

Shimuu

E, Nakamura

NCI-Navy

Medical

Y, Mukal

rhesdo, MD 20889.510.5.

(range h-72). (AUC)

was stud&

T. Hojo

Cancer

F et al.

Insrilure.

in 14 patients with non-small half-lift

was 34.3 min

drug conccn~a110n

of disulbution

The mean maximum

was 17X @ml

(12-540)

was 308 ng/ml(17-

in lhc one-compartment

cell curve

plasma drug

activity.

cylolox~c

individuals

wcrc

1423). The mean volume

model was 0.1X3

was considerable

Iowcr

I/kg (O.OlO-

doxorublcin ICI

drug resistant (MDR)

human lcukacmia

H69P.

10 pmol/l.

ICI

was significanlly

in reducing

In rcs~stant

accumulalion

the IC,,

cells.

ICI

in small-cell

\ersos

ihan lamoxfifcn.

is an cffcc~~~c modulator

Bclwccn

April

study comparmg

cisplatmat80mg/m*lVonday I, 3, and 5 (PE);

(IV)

regimens with ihc same

I andctoposidcat

or CAV altcmaling

the sludy,

forPE,andW PE (76%)

the complctc rcsponsc r&s Nine (23%) rcgnncn

hlghcr

of daunomycin

0x01

wcrc entered

Ilospilols,

Baldingersrrasse.

the maximum

rcspondcd

to PE when

they were

The rcsponsc duratlon

longer than thal with CAV (11.8

months) (P=.O27) wl1h hmllcd

months)

(P=.OO4).

was superior

tolerance

with

l-3.

FIX

a fixed

paucnlz

Marburg.

Ann

of combined

dose ofcarboplatm

wcrc

dose level. The dally

following

level

doses of ctoposldc glvcn

starting

of 5 pal~cnis. Lcuko-

or thrombocytopcma

m O/5 of ihc palicnls

a1 the dose lcvcls

140 mg/m’, cffccls

wcrc mild rcmissIon

SUWIV~I

progression-free

prcdominanlly survival

iotallcd

cxlcnsivc-slagc

SCLC,

mcndcd

pro1ocols.

tismg

was idcnuficd

incrcasc

is a well m~crvals

in

side

and vommng

12%

and median

rcsul1s rndlcate

rolcratcd

ra1cs comparable

ucaoncnl

Olher

was 9.3 months

in combina1ion

as 140 mg/m’

in 114 of

rate was 40% with a

4.3 months. These

with rcsponsc

dose ofcloposidc

Thus,

ofnausca

response

in m 3

a1 a level of

dose of 160 mg/m’.

The overall

ra1c. mcdmn

occurred

grade 3 or 4 occurred

of 160 mg/m’.

a1 an ctoposldc

and consisted

WHO

and every

was mcreased

in 2/5 of 1hc patients

and 3/5 pat~cms a1 a lcvcl

was sroppcd

(300 mg/

of 80 and 100 mg/m’,

the pat~cnls at the lcvcl of 120 mg/m’, dosage

ca-

with 80 mgf

[his smrtmg

dose of ctoposldc

97

m the PE arm (P=.O23).

In

after fading to were

on CAV/PE

was

The survival

time

to Ihat with

in the altcrnatmg

canlly superior to the survival in Ihe CAV

CAV

(9.9

In pallems

arm was signifi-

arm (P=.O14)

or the survival

The LOX~Ccffccts wcrc acceptable in all three

rcguncns. Thcsc rcsulw favor the &mating

spy over cilhcr standard chcmothcrapy. lhc dlffcrcncc?

were trcaicd

m* iv on day I) and cscalatmg

standard

crossed over.

or that with PE (9.9 momhs) (P=.O56).

dlscasc, lhc survival

chcmothcrapy

cancer (SCLC)

carboplalin/ctoposldc

lb%, and 15%. respcc-

suggcsung that these two regimens

non-cross-resistant.

CAViPE

D-3550

wi1hcxtcnsivestagesmall-celllung

that combined

whde

K.

of IlemnrologylOncology,

rcglmen

m

1othosc ofolher

of 4 weeks

the recom-

with 300 mg/m2carboplalin

IV for 3 consccutivc days.

of 39 patients who failed LOrespond to the imtial

respond lo the PE rcgimcn,

with

W, Drings P, Havemann

Division

in

rates forPE(78%)andCAV/ (55%).

inextensivestagesmall-

1991:2:361-4.

complelc

Each regimen

paticnls

than 1hc rate for CAV

wcrc .\lrndar (14%.

from rcs~stanl cells

of MDR.

of lnrernalMedicine.

in 14/25 of 1hc paucms.

100mg,/m*IVondays

COnUasl, only one (8%) of 13 patients responded lo CAV

slgnificanlly

at 50

I (CAV);

for analysis (97 for CAV,

forCAV/PE).Thcrcsponsc

wcrc signiflcan1ly

IV on day

with PE (CAV/PE).

and 288 of lhcm wcrc chgiblc

lung

cyclophosphamide

on day 1, doxorubicin

at 1.4 mg/m’

wan rcpca1cd cvcry 3-4 weeks. Three hundred

more

Thcsc studies suggest 1hac ICI 164384

incrcmcnls of20 mgJm2 iv un11l scvcrc myclosupprcssion

llahrkrno

basis in paucn& with small-cell

mg/m” IV on day 1, and vincrislmc

parGaIly

Te1

1988, WC conducted a randomued

al a dose of 800 ms/m2 muavenously

CAV

H, Tamura

Preferrural

Osakn

cancer. The patlcnls wcrc randomly a.ss~gncdto rexve

tlvely).

and vincristine

of these regimens

Y, lkcgami

two standard chcmothcrapy

regimens glvcn on an allcmating

‘H-daunomycin

from 2.5 IO IOpmol/

Tesscn H-W, Gocrg C, Achicnath

m2 IV on days

1985 and May

(1.2-6-fold)

in the CEM/VLB

and was signlfGinlly

Determiningcarhoplatin/etoposidedosage

Philipps-Universuy

J Nad Cancer Ins1 1991;83:855-61.

Ilos~~~ol.

effecove

cell long cancer (SCLC)

and the

doxorobicin,

of lnwnal Medrcu~e.

al. Deparmwzr

100 and

theoestrogen

increased

manner

164384 rcduccd !IIC efflux

more effcctlvcly

of milomycm,

alternation

K, Sai~o N. Nlshiwakl

more

than lamoxifcna1conccnlrauonsranging

Depar~?~nl

lung cancer

Fukuoka M, Furusc

of

ranging from I.25 10

of doxorublcin 164384

in a dose-depcndcnl

In order IO define

and etoposide

non-

the two respective parental cell lines,

studlcs al concentrations

164384

than lamoxifcn

among

than those rcportcd after inlravc-

trial of cyclophosphamide,

ccl1 lines CEM/VLB

Noneoftbcsccclllincsexprcsscd

bopla1mlcloposidcdosagc.pa1icnls versus cisplatin

AI

the cyrotoxicily

manner in both the classical multi-

ICI 164384 had no cffccton

I. ICI

in vitro.

potentialed

1000 and the human small cell lung cancer cell line H69

CEM/CCRFand

effecuvc

entlrcly devoid of O~SUO-

resistance

164384

in a dose-depcndcnl

variation

nous admmistmllon.

Randomired

Ilospilal,

and hack-extrapolated

wilh respect LOthe pharmacokmctics and AUC

A, Huggins R cl General

WESI. VK 31X1. Eur J Cancer 1991:27:773-

modulates

concenuations,

doxorubicin

WolfM.

mean Cfmax)

TJ, Wakelmg Reparriatron

ICI 164384, a new steroidal antiocsuogcn, gcnic

was 1.91/mm

Thcrc

resistant

7.

0.887) and the rate constant for unchanged drug appearing m the urine (0.57-7.27).

Oncology,

Private Bag No. 1. Ileidelberg

100 line.

artcry mfus~on of 20 mg (I l.4-

The mean climmation

(C(max))

Be-

1991;27: 1046-U.

of hronchml

was 166 ng h/ml (39.312).

plasma

Narronal

and the arca under UIC plasma conccnuallon-lime

concentration

in

ofMedrcal

al. Department

receplor. In comparative

J. Tani K, Yamashu

Branch,

Eur J Cancer

The pharmacokmctics lung cancer (NSCLC).

of mitomycin

cell lung cancer

Oncology

14.0 mgfmz) mltomycin

infusion

in multi-drug

164384

LX4. artery

resistance

and lung cancer cells by the pure antioestrogen

Hu XF, Nadalin G, De Luisc M, Martm

CEMiVLB

for SCLC.

of doxorubicin

leukaemia

arc not dramatic.

such as CAV

chcmother-

and PE, although

Is cisplatinom-based

chemotherapy

small cell lung cancer? Report

useful

of a French

in disseminated

multicenter

non

randomized

trial Quoix E, Dietcmann JP et al. Pavilion

A, Charbonncau

Lwnnec.

CfIRU.

J. Boutin C, Mu-ice BP 426.67091

JC.Orlando

Srrasbourg

Cedex.

Bull Cancer 1991;78:341-6. The bcnefi1 small

cisplatinum higher

of chemotherapy

ccl1 lung canccr response

rates.

duc1cd a prospcc1ivc 10 vindcsmc

To

study

randomt/cd

ihc

pal~cnls with sugc IV NSCLC The 11ca~ncn1 groups

question

in disseminated Dcccmbcr

disseminated The mtmduction

for NSCLC

trial comparing

Bc1wccn

24 wcrc in 1hc chcmolhcrapy group.

chemolhcrapy

chemolhcrapy

+ cisplatm.

with

is controversial.

in 1he combination

cisplalinum-based

for pauents

(NSCLC)

of le

usefulness

NSCLC

care

1988,49 palrcnts

and 22 in the bcsl supportive different

of

we con-

best supportive

1985 and March

wcrc no1 significamly

of

gave rise lo

wcrc cnrollcd. Ofthc46eliglble group

non

Care

in lerms of