Binding of toremifene to plasma proteins

108s

C-028 BINDING

OF TOREMIFENE

SipilB,

H., NBntb,V.

Central The

Hospital,

in vitro

(300

000

strong

protein

x g,

unlabeled

was

bound

the

of

of

toremifene

cold

phoresis

toremifene

to

sensitive total

fractionate

tion

and

bound

about

2X

different

and

The

Of

by

University

by ultracentrifugation be used

and

to agarose

Localized 6X

99.7X

by

500

gel

using

ng/ml

electroposition-

by staining.Of

to

to

drug.

visualized

about

due

together

radioactivity

3H-toremifene

was

albumin,

total

exposed

were

not

3H-Toremifene

unlabeled

adding

were

proteins to

the

of the

radioactivity

the

Turku

could

membranes.

used.

samptes

bound

pre-alpha,-globulin

measured methods

and

studied

serum

that was

was

concentration

proteins. 92%

serum

was

Center,and

Finland.

filtration

filters

was

The

After

radioactivity

human

51700 nglml

proteins

different

Turku,

and

on the

Research

Ltd.,

assayed

plasma.

counter.

to

all

500,

standard

in

dialysis

to

50,

to to

Group

Chemistry.

toremifene

independent

proportional

protein

of

toremifene

proteins

Binding

Clinical

Equilibrium

toremifene,

to

t. Farmos

of

binding

6.5 hours). of

PROTEINS

Kangas,

Oepartment

adsorption

with

TO PLASMA and

the

beta-l-globulin

frac-

fraction_

c-029 TOLERANCE

AND EFFICACY

Stamm H.,

Roth

Kantonsspital

From

20

1985

with

or

100

to

August

to

DROLOXIFENE

He il

H. J.*,

Basle,

1986

droloxifene

after

sodium,

Stab

Frauenklinik,

single

laboratory

eight

IN

PATIENTS

WITH

ADVANCED BREAST CANCER

M. *

Switzerland;

*Klinge

postmenopausal

investigate

were

Tolerance

dose:

There

parameters

potassium,

hormones

A.,

Pharms

patients

tolerance,

kinetics

no effects

on vital

with and

GmbH,

advanced

8000

Miinchen,

breast

efficacy

after

cancer

single

F.R.G.

were

enrolled

and multiple

in

oral

phase

doses

X/II

with

mq tablets.

Tolerance Standard

OF THE ANTIESTROGEN

Almendral

Easel,

March

studies

R.,

calcium

were

such

as we.ll

as

SGOT,

SGPT,

Y-GT,

cosgulogremand

BY

functions LDH,

CPK,

hemograms

and

no reports

crestinine,

were

not

on any

urea,

affected.

other

serious

total bilirubin, Also no clinically

side

effectu.

blood glucose, relevant chanqss

observed.

after

multiple

doses:

Again

tulerance

was

excellent

and

the

only

occasional

side

effect

observed

were

hot

flushes. Efficacy

of

because the

of

treatment: death

response

over

was

22 months

months remission

Also

present

OF therapy stable

local of

were

start

Clinically

developed

screlosis

tumors

after

20 mg daily.

she

with

weeks

possible.

at

before

Measurable

four

with

is

20 mq one The

lesions,

five

to

evident

patient third

now holding

patients.

refusion

disease

recurxwrxe.

most

in

or

in

had

further

a patient

with

of

of

In

with

could

three

isolated

node

mstastases

a period

patients

therapy.

a remission

patient on over

Three

continue

diffuse

metastases

OF the

16 months

be

evaluated

evaluation lung

over

sternum

under

not

patients

a period

of

experiences

treatment

of

metastases

with

11

partial 100

mg daily.

c-030 OROLOXiFENE: Ahlemann

INTERMITTENT

L.M.,

Heil

Kcankenhiiuser In

a pilot

des phase

day

with

100

All

patients

til

day

Besides

the tumor

as

3/1O In

disease

study

under

10

disease

end

experienced

complete

was

a period

until

LOdenscheid, cancer

a positive for week

* Klinge

were

receptor

response four,

investigations

treated

and

at

tolerance

in

were

performed

GmbH, 8000

intermittently

status

then

Pharma

the

wary

monthly

Mijnchen

every

time

of

day

after

80,

second

primary

F.R.G.

or

third

operation.

start

of

therapy

un-

intervals. and

endocrine,

standard

laboratory

as

monitored. of

diagnosed

of

breast

had

monitored

remissions

remission over

were

intervals

wre

5880

metastatic

patients

pharmacokinetic

parameters

treatment

All

weekly

assessment

partial

with

p.o.

in

BREAST CANCER

Strshlentherapie,

patients

associated

patients

METASTATIC

Kreises,

evaluable

clinical

IN

H..J.*

droloxifene

thereafter

patients four

II

had

THERAPY Stab

MBrkischen

mq of

seven,

well

M.:

seven

osseous with

months.

and

soft

a duration In

two

tissue

metastasis

between

patients

3 and

the

tumor

fasting

7+ months. was

between

6 and

One patient

progressive

had

despite

19+

months.

stable

antiestrogenic

treatment. Tolerance Time

of

courses

disease

before

droloxifene of

the clinical

tumor

treatment

was

associated confirmation

excellent, antigens

,

thus

hot

flushes

were

213

ceees

reflected being

helpful

in

observed with

predicting

occasionally

complete response

in

remission to

therapy.

some patients. and

both

cases

of

progressive

of