A phase II trial of capecitabine concomitantly with whole-brain radiotherapy followed by capecitabine and sunitinib for brain metastases from breast cancer.
BACKGROUND
Brain metastasis from breast cancer presents a significant threat to women's health and quality of life. Capecitabine and sunitinib have shown some activity in this setting; therefore, we conducted a single-arm phase II trial with these agents.


METHODS
Patients with breast cancer and central nervous system (CNS) metastases received whole-brain radiotherapy concurrently with capecitabine (1,000 mg/m(2) per day for 14 consecutive days), followed by concomitant capecitabine (2,000 mg/m(2) per day for 2 weeks followed by a 1-week break) and sunitinib (37.5 mg daily, continuously). The primary endpoint was progression-free survival (PFS).


RESULTS
Of 25 planned patients that would be required to detect a 4-month improvement (from 5 to 9 months) in median PFS with 80% power, 12 were enrolled, and the study was then closed for slow accrual. Median PFS was 4.7 months, and median overall survival was 10 months. In the CNS, 25% had progressive disease, and 83% experienced extra-CNS progression. The most common side effects were fatigue and nausea.


CONCLUSIONS
In 12 evaluable patients studied, concurrent capecitabine and whole-brain radiation followed by capecitabine and sunitinib did not extend PFS over historical rates and was associated with significant toxicity. Our study was small and closed due to slow accrual.
Baylor College of Medicine, Houston, Texas, USA; niravath@bcm.edu.
Polly
P
Niravath
Baylor College of Medicine, Houston, Texas, USA;
Yee Lu
YL
Tham
Baylor College of Medicine, Houston, Texas, USA;
Tao
T
Wang
The Methodist Hospital, Houston, Texas, USA;
Angel
A
Rodriguez
Baylor College of Medicine, Houston, Texas, USA;
Claudette
C
Foreman
Baylor College of Medicine, Houston, Texas, USA;
Susan G
SG
Hilsenbeck
University of Texas, San Antonio, Texas, USA.
Richard
R
Elledge
Baylor College of Medicine, Houston, Texas, USA;
Mothaffar
M
Rimawi
D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000069287:Capecitabine; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D000077210:Sunitinib
D007211:Indoles; D011758:Pyrroles; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000077210:Sunitinib