A multicentre, randomized, pharmacokinetic, endocrine and clinical study to evaluate formestane in breast cancer patients at first relapse: endocrine and clinical results. The Italian Trials in Medical Oncology (I.T.M.O.) group.
BACKGROUND
In postmenopausal breast cancer (BC) patients, tamoxifen (TAM) is frequently used in first-line therapy, and for those relapsing under TAM, aromatase inhibitors would be the drug of choice. Formestane, a new aromatase inhibitor, has been demonstrated to be as effective as TAM in first-line therapy. This trial was carried out to investigate the pharmacokinetics and antitumor activity of two formestane doses in BC patients at first relapse, as well as their effects on estrogen levels, evaluated by means of a new analytical method.


METHODS
One hundred fifty-two postmenopausal BC patients were randomly given formestane 250 mg or 500 mg intramuscularly every two weeks. The blood samples for estrogen measurements were taken on the first day of therapy, at 4 and 10 weeks, and every 12 weeks thereafter. Tumor response was first evaluated after 2.5 months, and then every three months.


RESULTS
Seventy-three patients received formestane 250 mg and 79 received 500 mg. After four weeks, plasma estrone, estradiol and estrone sulphate levels were significantly (P < 0.001) suppressed in both groups. The overall response rates were 30% and 40% on 250 mg and 500 mg, respectively.


CONCLUSIONS
Both of the formestane doses are effective in reducing plasma estrogen levels in BC patients at first relapse, and the new analytical method improved the quality of results. The antitumor response was highly satisfactory.
Bajetta
E
E
Division of Medical Oncology B, Instituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Zilembo
N
N
Barni
S
S
Noberasco
C
C
Martinetti
A
A
Ferrari
L
L
Schieppati
G
G
Buzzoni
R
R
Jirillo
A
A
Amichetti
M
M
D'Aprile
M
M
Comella
G
G
Bichisao
E
E
Bolelli
G F
GF
Attili
A
A
Bombardieri
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000735:Androstenedione / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy*; D004958:Estradiol / Q000097:blood*; D004970:Estrone / Q000097:blood*; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008875:Middle Aged; D017698:Postmenopause; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004970:Estrone; D000735:Androstenedione; D004958:Estradiol; C014594:formestane