A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients with androgen-independent prostate cancer.
OBJECTIVE
Thalidomide is a potent teratogen that causes dysmelia in humans. Recently, in vitro data suggested that it inhibits angiogenesis. Prostate cancer is dependent on the recruitment of new blood vessels to grow and metastasize. Based on those data, we initiated a Phase II trial of thalidomide in patients with metastatic androgen-independent prostate cancer.


METHODS
This was an open-label, randomized Phase II study. Thalidomide was administered either at a dose of 200 mg/day (low-dose arm) or at an initial dose of 200 mg/day that escalated to 1200 mg/day (high-dose arm).


RESULTS
A total of 63 patients were enrolled onto the study (50 patients on the low-dose arm and 13 patients on the high-dose arm). Serum prostate-specific antigen (PSA) decline of > or = 50% was noted in 18% of patients on the low-dose arm and in none of the patients on the high-dose arm. Four patients were maintained for > 150 days. The most prevalent complications were constipation, fatigue, neurocortical, and neurosensory.


CONCLUSIONS
Thalidomide, an antiangiogenesis agent, has some activity in patients with metastatic prostate cancer who have failed multiple therapies. A total of 27% of all patients had a decline in PSA of > or = 40%, often associated with an improvement of clinical symptoms. Because our preclinical studies had shown that thalidomide increases PSA secretion, we believe that the magnitude of PSA decline seen in our trial justifies further study.
Figg
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WD
Medicine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. wdfigg@helix.nih.gov
Dahut
W
W
Duray
P
P
Hamilton
M
M
Tompkins
A
A
Steinberg
S M
SM
Jones
E
E
Premkumar
A
A
Linehan
W M
WM
Floeter
M K
MK
Chen
C C
CC
Dixon
S
S
Kohler
D R
DR
Krüger
E A
EA
Gubish
E
E
Pluda
J M
JM
Reed
E
E
D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000502:physiology; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000097:blood; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000187:drug effects; D005500:Follow-Up Studies; D006801:Humans; D008222:Lymphokines / Q000097:blood / Q000187:drug effects; D008233:Lymphotoxin-alpha / Q000097:blood; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000139:chemically induced; D009389:Neovascularization, Pathologic / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D013792:Thalidomide / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000728:Androgens; D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D008222:Lymphokines; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide; D017430:Prostate-Specific Antigen