Efficacy, safety, and potential biomarkers of thalidomide plus metronomic chemotherapy for advanced hepatocellular carcinoma.
OBJECTIVE
Thalidomide has been shown to have antitumor activity in some patients with advanced hepatocellular carcinoma (HCC). We initiated a phase II study to determine the safety and efficacy of adding metronomic chemotherapy to thalidomide as first-line therapy.


METHODS
This open- labeled, single-arm, multicentered, investigator-initiated study enrolled patients with treatment-naïve advanced HCC not amenable to locoregional therapies. Treatment included oral thalidomide (100 mg twice daily) and tegafur/uracil [125 mg/m(2) (based on tegafur) twice daily]. Tumor assessment was performed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Pretreatment plasma levels of angiogenesis factors were correlated with patient outcomes.


RESULTS
Forty-three patients were included. Sixteen (37%) patients had a Cancer of the Liver Italian Program (CLIP) score of 4, and 31 (72%) patients had chronic hepatitis B virus infection. The objective response rate was 9%, and the disease stabilization rate was 33%. The median progression-free survival was 1.9 months (95% CI 1.7-2.1 months), and the median OS was 4.6 months (95% CI 2.3-6.9 months). Treatment was generally tolerable. High baseline plasma levels of interleukin (IL)-6 and IL-8 were adversely correlated with patient survivals.


CONCLUSIONS
The combination of thalidomide and tegafur/uracil was safe and demonstrated modest activity in patients with advanced HCC.
Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan, ROC.
Yu-Yun
YY
Shao
Zhong-Zhe
ZZ
Lin
Chiun
C
Hsu
Kuan-Der
KD
Lee
Chi-Huang
CH
Hsiao
Yen-Shen
YS
Lu
Chien-Chung
CC
Huang
Yin-Chun
YC
Shen
Chih-Hung
CH
Hsu
Ann-Lii
AL
Cheng
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D013792:Thalidomide / Q000008:administration & dosage*; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D015850:Interleukin-6; D016209:Interleukin-8; D013792:Thalidomide