A phase II trial of vorinostat (suberoylanilide hydroxamic acid) in metastatic breast cancer: a California Cancer Consortium study.
OBJECTIVE
The primary goal of this trial was to determine the response rate of single-agent vorinostat in patients with metastatic breast cancer. The secondary goals included assessment of time to progression, evaluation of toxicities, and overall survival.


METHODS
From June 2005 to March 2006, 14 patients received vorinostat, 200 mg p.o., twice daily for 14 days of each 21 day cycle. Response and progression were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.


RESULTS
The median age for all patients was 60.5 years (range, 37-88). Eight patients were estrogen receptor and/or progesterone positive, four were Her-2 positive. Sites of metastatic disease included brain, liver, lungs, bones, pelvis, pleura, chest wall, and distant lymph nodes. Patients received a median of 1.5 prior (range, 0-2) chemotherapeutic regimens for metastatic disease. Fatigue, nausea, diarrhea, and lymphopenia were the most frequent clinically significant adverse effects. The median number of cycles delivered was 2 (range, 1-20). There were no complete or partial responses, and the study was terminated after the first stage; however, 4 patients were observed with stable disease with time to progression of 4, 8, 9, and 14 months. The median number of months that patients received treatment on this study was 1.7 (range, 0.5-14).


CONCLUSIONS
Although not meeting the RECIST response criteria for adequate single-agent activity, the observed tolerable toxicities and the potential for clinical benefit in terms of stable disease suggest that further assessment of vorinostat as a part of combination therapy with either chemotherapeutic or targeted agents in metastatic breast might be undertaken.
Luu
Thehang H
TH
Division of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Duarte, California 91010, USA.
Morgan
Robert J
RJ
Leong
Lucille
L
Lim
Dean
D
McNamara
Mark
M
Portnow
Jana
J
Frankel
Paul
P
Smith
David D
DD
Doroshow
James H
JH
Wong
Carol
C
Aparicio
Ana
A
Gandara
David R
DR
Somlo
George
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D000077337:Vorinostat
D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D000077337:Vorinostat