Combination therapy for treatment of female breast cancer

DETAILED DESCRIPTION OF THE INVENTION In one preferred aspect, the present invention provides an effective method of treating breast cancer in warm-blooded female animals in need of such treatment by administering an LH--RH agonist or antagonist, in association with an antiandrogen and an inhibitor of sex steroid biosynthesis or pharmaceutical compositions thereof in amounts sufficient to inhibit breast tumor growth.
These active compounds can be administered together or in any order as discussed hereinafter.
To assist in determining the effect of the treatment, blood plasma concentrations of the sex steroids of adrenal origin, i.
e.
, adrenal androgens and estrogens, and tumor size are measured.
Lowered concentrations of sex steroids and reduction in tumor size are indicative of successful treatment, e.
g.
inhibition of tumor growth using active compounds described herein in accordance with the present invention.
The concentrations of adrenal androgens and estrogens such as dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), androst-5-ene-3.
beta.
, 17.
beta.
-diol (.
DELTA.
.
sup.
5 -diol) and, the ovarian estrogen, 17.
beta.
-estradiol (E.
sub.
2) are measured by standard methods well known to those skilled in the art, see for example F.
Labrie et al.
, The Prostate, 4, 579-594 (1983).
The change in tumor size is measured by standard physical methods well known to those skilled in the art, e.
g.
, bone scan, chest X-ray, skeletal survey, ultrasonography of the liver and liver scan (if needed), CAT-scan and physical examination.
While a LH--RH agonist or a LH--RH antagonist may be used in one preferred aspect of the present invention, the use of a LH--RH agonist is more preferred.
By the term "LH--RH agonist" is meant synthetic analogues of the natural luteinizing hormone-releasing hormone (LH--RH), a decapeptide of the structure: L-pyroglutamyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-glycyl-L-leucyl-L- arginyl-L-prolylglycyl-NH.
sub.
2 Typical suitable LH--RH agonists include nonapeptides and decapeptides represented by the formula: L-pyroglutamyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-X-Y-L-arginyl-L-pr olyl-Z wherein X is D-tryptophyl, D-leucyl, D-alanyl, iminobenzyl-D-histidyl, 3-(2-naphthyl)-D-alanyl, O-tert-butyl-D-seryl, D-tyrosyl, D-lysyl, D-phenylalanyl or N-methyl-D-alanyl and Y is L-leucyl, D-leucyl, N