Randomized phase III trial of tamoxifen versus thalidomide in women with biochemical-recurrent-only epithelial ovarian, fallopian tube or primary peritoneal carcinoma after a complete response to first-line platinum/taxane chemotherapy with an evaluation of serum vascular endothelial growth factor (VEGF): A Gynecologic Oncology Group Study.
OBJECTIVE
To compare progression-free survival (PFS), overall survival (OS) and toxicities of thalidomide versus tamoxifen and to evaluate serum vascular endothelial growth factor (VEGF) in biochemical-recurrent epithelial ovarian cancer, primary peritoneal cancer or fallopian tube carcinoma (EOC/PPC/FTC).


METHODS
Biochemical recurrence was defined as a rising CA-125 exceeding twice the upper limit of normal without evidence of disease as defined by RECIST 1.0 criteria. Women with FIGO stages III and IV, histologically confirmed EOC/PPC/FTC who were free of disease following first-line chemotherapy were randomized to oral thalidomide 200mg daily with escalation to a maximum of 400 mg or tamoxifen 20mg orally twice daily for up to 1 year, progression or adverse effect prohibited further treatment. VEGF was quantified by ELISA in pre and post-treatment serum.


RESULTS
Of the 139 women randomized, 138 were eligible. Interim analysis showed that thalidomide did not reduce the recurrence rate relative to tamoxifen, and the trial was closed. Thalidomide versus tamoxifen was associated with a similar risk of progression (HR = 1.31, 95% confidence interval [CI] = 0.93-1.85), an increased risk of death (HR = 1.76, 95% CI = 1.16-2.68) and more grades 3 and 4 toxicities (55% versus 3%). The most common grades 3 and 4 toxicities were constitutional (12%), somnolence (12%), pulmonary (9%), venous thromboembolism (VTE) (6%) and peripheral neurologic (6%) for thalidomide, with VTE (1.4%) and gastrointestinal (1.4%) for tamoxifen. Serum VEGF was not associated with clinical characteristics, treatment, PFS or OS.


CONCLUSIONS
Thalidomide was not more effective than tamoxifen in delaying recurrence or death but was more toxic. VEGF was not prognostic in this cohort.
Hurteau
Jean A
JA
NorthShore University Health System Division of GYN Oncology, Department of Obstetrics and Gynecology, University of Chicago Pritzker School of Medicine, Evanston Hospital, Evanston, IL 60201, USA. jhurteau@uchicago.edu
Brady
Mark F
MF
Darcy
Kathleen M
KM
McGuire
William P
WP
Edmonds
Pamela
P
Pearl
Michael L
ML
Ivanov
Iouri
I
Tewari
Krishnansu S
KS
Mannel
Robert S
RS
Zanotti
Kristine
K
Benbrook
Doris M
DM
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D018394:CA-125 Antigen / Q000097:blood; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005185:Fallopian Tube Neoplasms / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000097:blood / Q000188:drug therapy*; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D043823:Taxoids / Q000008:administration & dosage; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D020533:Angiogenesis Inhibitors; D018931:Antineoplastic Agents, Hormonal; D001952:Bridged-Ring Compounds; D018394:CA-125 Antigen; D009944:Organoplatinum Compounds; D043823:Taxoids; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013629:Tamoxifen; C080625:taxane; D013792:Thalidomide