Table 3.
Clinical trials targeting androgen in hepatocellular carcinoma
| Drug (dosage) | Randomized study | Number of patients | Eligibility Child-Pugh class | Stage of HCC | Efficacy: mean survival or response | Ref |
|---|---|---|---|---|---|---|
| Leuprorelin, flutamide, and tamoxifen | Yes | 192 | Child-Pugh Class A/B/C: 112/50/2; cirrhosis, 90%; ascites, 26%; HBV, 3%; HCV, 19% | Okuda’s classification stage I/II/III: 81/107/4 | 135.5 d (P=0.21) | 108 |
| Tamoxifen (administered until death) | Yes | 184 | Child-Pugh Class A/B/C: 105/59/5; cirrhosis, 93%; ascites, 31%; HBV, 10%; HCV, 13% | Okuda’s classification stage I/II/III: 93/83/8 | 176 d | 108 |
| Flutamide for 8 weeks | Phase II | 32 | Measurable advanced HCC patients; hepatitis-related, 88% | AJCC stage III/IV: 5/27 | 10 wks; 9 of 22 (41%), stable diseases; 13 (59%), progress diseases | 109 |
| Antiandrogen (Anandron) plus placebo | Yes | 58 | Unresectable HCC; cirrhosis, 76%; HBV, 25% | N/A | 3.6 mo (NS); 1, complete response | 110 |
| LHRH agonist plus placebo | Yes | 61 | Unresectable HCC; cirrhosis, 85%; HBV, 21% | N/A | 2.7 mo (NS); 1, partial response | 110 |
| Antiandrogen plus LHRH agonist | Yes | 60 | Unresectable HCC; cirrhosis, 82%; HBV, 14% | N/A | 3.9 mo (NS); 1, partial response | 110 |
| Placebo plus placebo | Yes | 59 | Unresectable HCC; cirrhosis, 83%; HBV, 35% | N/A | 5.8 mo | 110 |
| Cyproterone acetate | No | 25 | Cirrhotics with unresectable HCC | N/A | 14 wks; 5, excess in 29 wks; 5, response | 111 |
| Ketoconazole | No | 8 | Unresectable HCC | N/A | 6, <8 weeks | 112 |
| D-Tryptophan-6-luteinizing hormone–releasing hormone | No | 17 | Cirrhotics with HCC | N/A | No response | 113 |
| LHRH-analog triptorelin and tamoxifene | Yes | 33 | Child-Pugh: 7.7±2.0 (untreated HCC); cirrhosis, 27; HBsAg (+), 69.7%; anti-HDV (+), 15.2%; anti-HCV (+), 12.1% | Okuda stage I/III (%): 27.3/18.2 | 282 d (P=0.020 vs placebo) | 114 |
| Triptorelin plus flutamide | Yes | 23 | Child-Pugh: 8.3±1.6 (untreated HCC); cirrhosis, 18; HBsAg (+), 56.5%; anti-HDV (+), 8.7%; anti-HCV (+), 8.7% | Okuda stage I/III (%): 21.7/13.0 | 112 d (NS vs placebo) | 114 |
| Placebo | Yes | 29 | Child-Pugh: 8.9±2.1 (untreated HCC); cirrhosis, 25; HBsAg (+), 58.6%; anti-HDV (+), 10.7%; anti-HCV (+), 20.0% | Okuda stage I/III (%): 24.1/17.2 | 127 d | 114 |
Abbreviations: AJCC, American Joint Committee on Cancer; HBV, hepatitis B virus; HCV, hepatitis C virus; HDV, hepatitis delta virus; HBsAg, hepatitis B virus surface antigen; LHRH, luteinizing hormone-releasing hormone; HCC, hepatocellular carcinoma; Ref, references; NS, not significant; N/A, not applicable; d, days; wks, weeks; mo, months; vs, versus.