A pilot study with an ifosfamide, carboplatin and etoposide regimen (ICE) in patients with advanced non-small-cell lung cancer

207

16, Chuoku.

Sapporo

060. Cancer

Chemolher

Pharmacol

Drug Invest lYYO;2:31-7.

1990;26:373-

A phase I study wth

6. A tol;tl of 47 patients weretrcmed

with unresectable

witharcglmen

conslstmgofwplatin

lfosfamide(IFX,2g/m*x (CIV).

(CRs)

(CDDP.

was given over a 3. or 5.week

cvaluable

patienB,

19 partial

wved,forarcsponseratcof47.5%

I B in adeno-and

and 30.

lung cancer

were ohtamed.

large-cell

renal toxicitywasrather

(PRs)

were

no complete

toxicity

failure

and sepsis. We concluded

CIV

especially

carcinoma,

agamst

but more toxic than the combination

non-small-cell carefully

lung cancer and rhat candidates

that the

and VDS

Ihe combmation

was conducted

given

tic

following

carboplatin

75 mg/m”on

for

for ihis therapy must be

ifosfarmdc Ihcrapy,

were documcmcd, dose hmiting

toxicity

was Icucopema.

the exact activity

vanced NSCLC.

of life assessment

during

chemotherapy

for non-small

Maasiha

PK, Raulonen

JK, Mattson

uduztu 4. 00290 Quality wth

MT,

Mattson

KV.

Ilelsinki.

non-small

cell

Chcmothcrapy

Eur .I Cancer

lung

cancer

consisted

parliclpating

mfusion

hmitcd

600

(five dose levels)

Nme of the scales related

related to the disease itselfand

treatment

uncertainty

LO the major

Each paticm completed

known

Items (e.g. for nausea or appetite) the patlem’s

cycles of chemotherapy.

trial.

intrave-

to performance,

problems

about the value of ueatmcnt: side-effccls

on the last day of in the scores for

suggests that the method was useful

perceived

quality

Compliance

of life during

repeated

was good and the method

was

Oncology

oloalveolar

of interferon-alpha

Van ZandwiJk

N, Jassem E, Dubbclmann

ofMedical

Piesmanlaan

121.1066

IO patients

with

Oncology,

CXAmsu~dum. locally

between

1 and 10 MU

to 20 MU

dally.

dally

or exccssivc

for toxlcrty.

In 1 case ucatmcnt

loxlctly

fever, fatigue and progressive had malaw,

fatigue

could be detected. radiological

(IO months)

occurred.

Twentyman

Int I Cancer

2Qll.

after the start of Ihcrapy.

observed. These resulu

carcinoma

aerosol. weekly

Imtial

doses

and were then until

dwase

9 pauents wcrc evaluable

2 patients developed

fever, 1

and 2 had dose-dependent

to standard criteria no turnour responses for response Lo interferon,

of dlscase for 7-43

weeks (me&an

poml LO the fcasibihty

but also to its hmlted

advanced bronchioloalveolar

P.

Inslrlule,

15) was

of aerosol inhalauon

antitumour

PR. Medual

Rrsearch

Unir,

/fills

and cytotoxic

IFN-gamma

were

counting and aclonogcnic

natural

actiwty

of

m locally

carcmoma.

bronchioalveo-

lar carcinoma V, Camel1 K, Mat&on

Helsmki

Univerwy

Ear J Cancer

Cenrral

K. Deparrmem

Ijospilal,

ofFulmonory Medicine.

llaorlmaninkalu

4,00290

Six patients wilh diffuse bronchloalveolarcarcinoma

progressed treatment

effects

mvcstigatcd

There was considerable

thecclllincstothcIFNsm of IFN-treated markedly IFN

thrice

daily.

or bronchial

Therapy

IMsinki.

confined

by inhalation.

was continued

hyperreactwlty

in patients JP, Bron

Rrsprratorres.

IFN-a

and

duect

cell

human lung

10 an IFN,

that, where

only a small fractmn

were clonogemcally

the clonogcmc

hclerogcmxy

m the response of

of the cells remammg

wablc. When cell\

assay m the prcscncc of IFNs,

was diffcrcnt

Clonogcmcassay

a cell lme had responded after

wcrc placed mto

the t~mc course of colony

from that seen in the control culturca for mosL

with ADM

counting.

fracuon’ was greatly dependWhen

the effcct~

were studied, conclusions

of IFNs

regarding

in

the mtcr-

action of the effects of Ihe agents also depended upon the tlmc at which colomcs

were counted.

A randomized

study

comparing

cisplatin

or carhoplatin

poside in patients

with advanced

non-small-cell

pean OrgaoizHion

for Research

and Treatment

with

lung cancer: of Cancer

eto-

Euro-

Protocol

07861 Klastcrsky

I, Sculicr

/je#er-Border

The European (EORTC)

JP, Lacrolx

I. 1000 Brurlies Organuatmn

Lung Cancer

mg mainly

wth

and Trcatmcnt

cloposldc

Wcconcludc

IhatCDDPplus

than CBDCA

plus VP16

(VPlh:

100 mg/m2,

for saw&

and 202assess. rcsponscs (ORs;

difference

of myclosupprewon increased

trial

27 of 100 objcctivc

arm and 16 of 102 (16%)

sigmficamly

of Cancer

a randomI&

lungcanccr(NSCLC).Two

patients wcrc chglble

able for rcsponsc. WC obtamed m the CDDP

Rut,

I20 mg/m*, day 1) and carboplatm (CBDCA:

madvanccdnon-small-cell

hundred twenty-eight

./ule.\ Border.

lY9O;X: 1556.62.

Party conducted

I) mcombmatlon

325 mg/m*, day days I, 2,and3)

for Rcscarch

Working

comparmg c~splatin (CDDP:

H CL al. lnslirur J Clm Oncol

and renal

m the patients

in the CBDCA

m survival. functmn

rcccwng

consIs1-

Impairmcm,

the CDDP

VPl6wasmorcaclwe in advanced

arm (p =

Toxuty,

was

ucauncnt.

bulalsomorc

toxic

NSCLC.

became

Lo the

The dose was

unld

the tumour

unacceptable.

The

was not effective.

A pilot study with aa ifosfamide, Scalier

of purlfxxi usmg both

termsofgrowthinhibitlon.

cells indlcatcd

lreatmcnt

Non-P-glycoprotein precedes

with

advanced

D, Sergysels

lloprral

carboplatin non-small-cell R, Klaslersky

Sami-P~rre.

Universite

and etoposide

regimen

lung cancer J. Clinique Libre

des V&s

de Bruxelles.

mediated

P-glycoprotein

doxorobicin

mechanism

expression

for multidrug

during

in vitro

resistance

in a human

lung cancer

Baas F, Jongsma APM,

Broxterman

HJ ct al. Divisron

Bwlogy, (ICE)

CB2

1990;26:740-1.

thorax were treated with mwrferon-alpha 1 or 6 MU

C/mica1

Camhrldge

cancer cell lmes and for 2 of them also on thcu muludrug-rwslant

27%)

interferon-alphaondiffuse

Kmnula

Councd.

Road.

assay on a panel of 5 eslabhshcd

.07). Thcrc was no slgnifxant Effect of inhaled

lung

1990;46:546-51.

The antiproliferative recombmam

combination

had to bc slopped after 2 weeks due (0 dyspnoea.

was acccpt-

and both patrcnts

1990:26:738-40.

was contmued

In 6 out of 8 evaluated

stabilisauon

mtcrferon-alpha,

or thrice

and loss of appctltc

transient dyspnoea. According

Rumke

bronchioloalvcolar

as an inhaled

Trcalmcnc

progression

MCP, Cancer

Eur JCanccr

advanccd

were treated with interferon-alpha increased

R, Braat

The Nelherlands

400 mg/m* on

2) and autologous

assays in assessing the response of human

ent upon the time of colony

of bronchi-

carcinoma

Departmew

ranged

in the treatment

I and

by local Lhcrapy. Toxuty

of the cell lines. The measured ‘surviving application

ad-

wcrc ueatcd wth

;

and Radiorherapeuucs

formation

easily accepted by both patients and nurses as part of a routine.

Aerosol

NSCLC

to

wth

adriamycin

SAB,

counterparts.

of chemotherapy.

cycles. Variatron

The

lines to a and gamma interferons alone or in combina-

cell

Jabbar

on

intravenously

items wereassessed

the scales before treatmcnt,

(day 5) and once bctwccn

m estimating

mg/m’

m patients

6 g/m2 on day I carboplatm

followed

responses

A phase II study IS required

of short duration

The use of clonogenic cancer

tion with

scales for patients

m a phase I-II

of cyclophosphamide

nously on day 1 and uimctrexatc

two scales relalcd

of

1990:26:706-8.

days 1-S, repealed every 21 days. Elcvcn subjective hy the patmnts.

Deparrmen!

L~niversiryCen~ralllospilal,Ilaartman-

of hfc was assessed by linear analogue

75 mg/m’ was

no prior therapy.

days 1 and 2, and etoposidc 500 mg/mt on days bone marrow

3,

days

cell

lung cancer PulmonaryMedicine.Ijelslnki

wllh

01. the combmatlon

Two paficnts wth

1 to

X0 mg/m’on

carboplatm

all from the 7 patients

died 11 and 15 months, rcspcctlvcly, Quality

therapy wcrc

2 g/m’ on days

days 1 and 2, and ctoposidc

+

non-small-

on days 1 IO 3. In 15 treated patients, 3 objectlvc

able. Responses wcrc

chosen.

+ carboplatm

with advanced

Patients who had had prcwous

1 and 2. In those with no prcviow

dctermmc

of lfosfamidc

in patients

dosages:

high doses ICE (ifosfamlde

squamous-cell

of CDDP

(ICE)

admimstered

was not severe, but the

high;twopatwnlsdevelopedacuterenal

was more effective,

ob-

responses

and died of subsequentpancytopcnla rcglmen

40

insquamous-cellcarcinoma

carcmoma);

The hcmatologic

mg/m’)

period. Among

responses

(78.6%

ctoposide

cell lung cancer (NSCLC).

lOOmg/m),

3; with mcsna)andvindesine(VDS,3

Tlus regimen

completely

non-small-cell

TheNeiherlands

Amverdam. Two (MDR)

Cancerlnsliiute.

resistance selection

for

cell line

Pla.wumlann

ofMolecular 121,1066

CX

Cancer Rcs 1990;50:5392-8.

dlffercnt

mechanisms

lhat contrlbutc

were found m dcrwatives

cell line SW-1573.

The parental

to muludrug

resistance

of the human squamous lung cancer ccl1 lmc has a low amoum of mdrl

P-