Randomised double-blind trial of megestrol acetate vs placebo in treatment-naive advanced hepatocellular carcinoma

P K H Chow, D Machin, Y Chen, X Zhang, K-M Win, H-H Hoang, B-D Nguyen, M-Y Jin, R Lobo, M Findlay, C-H Lim, S-B Tan, M Gandhi, K-C Soo, Asia-Pacific Hepatocellular Carcinoma Trials Group, P K H Chow, D Machin, Y Chen, X Zhang, K-M Win, H-H Hoang, B-D Nguyen, M-Y Jin, R Lobo, M Findlay, C-H Lim, S-B Tan, M Gandhi, K-C Soo, Asia-Pacific Hepatocellular Carcinoma Trials Group

Abstract

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. We tested megestrol acetate (MA) against placebo in the treatment of advanced HCC.

Methods: From 2002 through 2007, this randomised double-blind trial enrolled 204 patients with treatment-naive advanced HCC (Eastern Cooperative Oncology Group (ECOG) performance rating of 0-3) from specialist care centres in six Asia-Pacific nations. Patients received placebo or MA (320 mg day(-1)). End points were overall survival (OS) and quality of life.

Results: An adverse but not statistically significant difference in OS was found for MA vs placebo: median values 1.88 and 2.14 months, respectively (hazard ratio (HR)=1.25, 95% CI=0.92-1.71, P=0.16). However, OS was similar among patients of good functional status (Child-Pugh A and ECOG 0, 1 or 2) (44.3%) in both treatment groups, with the adverse effect of MA confined to those of poor status. Megestrol acetate patients had a worse global health status (not statistically significant) but reduced levels of appetite loss and nausea/vomiting.

Conclusion: Megestrol acetate has no role in prolonging OS in advanced treatment-naive HCC. Overall survival with placebo differed markedly from that in similar trials conducted elsewhere, suggesting therapeutic outcomes may be strongly dependent on ECOG status and Child-Pugh score.

Figures

Figure 1
Figure 1
Consort diagram.
Figure 2
Figure 2
AHCC02 Kaplan–Meier estimates of OS. (A) OS by treatment. (B) OS in good and poor risk groups as defined by Child-Pugh class and ECOG performance status.
Figure 3
Figure 3
Changes in EORTC GHS over time by treatment group with the fitted model for the first 12 months post-randomisation.
Figure 4
Figure 4
Forest plot for the treatment comparisons within each Child-Pugh and ECOG groups.

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Source: PubMed

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