Effects of high dose raloxifene in selected patients with advanced breast carcinoma.
BACKGROUND
An earlier trial of raloxifene, conducted in women with metastatic breast carcinoma who initially had responded to tamoxifen and subsequently developed disease progression, suggested no antitumor activity for raloxifene in tamoxifen-refractory disease. However, preclinical studies and preliminary clinical data in healthy women suggest that raloxifene antagonizes growth of estrogen-dependent neoplasia.


METHODS
Raloxifene HCl 150 mg twice daily was given to 22 postmenopausal women with metastatic (American Joint Committee on Cancer Stage IV) or locoregionally recurrent, initially estrogen receptor positive breast carcinoma. Prior systemic treatment of metastatic disease was not allowed. Prior adjuvant chemotherapy or hormonal therapy was required to have been completed at least 1 year before study entry. Tumor response was evaluated every other month either radiographically or by physical examination. Evaluable disease was defined as bidimensionally measurable lesions.


RESULTS
Twenty-one patients were eligible for efficacy analysis; 6 had been treated previously with tamoxifen. There were no complete tumor responses. Four patients (19%; 95% confidence interval [95% CI], 2.2%, 36%) had partial tumor responses lasting 6.3, 17.5, 23.9, and 28.1 months, respectively. Prolonged stable disease (i.e., tumor size stable for > or = 6 months) was observed in 3 patients (14%; 95% CI, 0.0%, 29%) and lasted 7.9, 12.2, and 25.1 months, respectively. Combining partial responses and prolonged stable disease yielded an overall clinical benefit rate of 33% (95% CI, 13%, 53%). Adverse events generally were consistent with the disease state; there were no serious adverse events or laboratory changes believed to be therapy-related.


CONCLUSIONS
Raloxifene HCl, 150 mg, administered twice daily was safe, well tolerated, and modestly effective in highly selected postmenopausal women with advanced breast carcinoma. Further study of high dose raloxifene as monotherapy for advanced breast carcinoma most likely is unwarranted.
Gradishar
W
W
Northwestern University, Chicago, Illinois, USA.
Glusman
J
J
Lu
Y
Y
Vogel
C
C
Cohen
F J
FJ
Sledge
G W
GW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary; D016001:Confidence Intervals; D018450:Disease Progression; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009367:Neoplasm Staging; D017698:Postmenopause; D011788:Quality of Life; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D012074:Remission Induction; D012449:Safety; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride