Multicenter phase II study of oral bexarotene for patients with metastatic breast cancer.
OBJECTIVE
Bexarotene is a retinoid X receptor-selective retinoid that has preclinical antitumor activity in breast cancer. We evaluated the efficacy and safety of oral bexarotene in the treatment of patients with metastatic breast cancer.


METHODS
The following three groups of patients were treated: hormone-refractory, chemotherapy-refractory, and tamoxifen-resistant patients. Patients in the first two groups were treated with bexarotene alone, whereas the tamoxifen-resistant patients received both tamoxifen and bexarotene. Patients in all groups were randomly assigned to receive bexarotene at either 200 or 500 mg/m(2)/d.


RESULTS
One hundred forty-eight patients were randomized; 145 patients were treated. Of 48 hormone-refractory patients, there were two partial responses (6%) and 10 patients with stable disease lasting more than 6 months; of 47 chemotherapy-refractory patients, there were two partial responses (6%) and five patients with stable disease; and of 51 tamoxifen-resistant patients, there was one partial response (3%) and 11 patients with stable disease. All partial responses occurred at the 200-mg/m(2)/d dose. The projected median time to progression across all of the arms was 8 to 10 weeks. There were no drug-related deaths, and only two patients had drug-related serious adverse events. The most common drug-related adverse events were hypertriglyceridemia (84%), dry skin (34%), asthenia (30%), and headache (27%). There were no cases of pancreatitis.


CONCLUSIONS
The efficacy of bexarotene in patients with refractory metastatic breast cancer is limited. However, it is an oral agent with minimal toxicity and a unique mechanism of action, which produced clinical benefit in approximately 20% of patients. Future efforts should define populations likely to benefit from this agent.
Esteva
Francisco J
FJ
University of Texas M.D. Anderson Cancer Center, and Baylor College of Medicine, Houston, Texas 77030, USA. festeva@mdanderson.org
Glaspy
John
J
Baidas
Said
S
Laufman
Leslie
L
Hutchins
Laura
L
Dickler
Maura
M
Tripathy
Debu
D
Cohen
Roger
R
DeMichele
Angela
A
Yocum
Richard C
RC
Osborne
C Kent
CK
Hayes
Daniel F
DF
Hortobagyi
Gabriel N
GN
Winer
Eric
E
Demetri
George D
GD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000077610:Bexarotene; D001943:Breast Neoplasms / Q000097:blood / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013963:Thyroid Hormones / Q000008:administration & dosage / Q000097:blood; D017312:Toremifene / Q000008:administration & dosage; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013764:Tetrahydronaphthalenes; D013963:Thyroid Hormones; D013629:Tamoxifen; D017312:Toremifene; D000077610:Bexarotene