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Phase 1/2 study of everolimus in advanced hepatocellular carcinoma
Article first published online: 27 APR 2011
Copyright © 2011 American Cancer Society
Volume 117, Issue 22, pages 5094–5102, 15 November 2011
How to Cite
Zhu, A. X., Abrams, T. A., Miksad, R., Blaszkowsky, L. S., Meyerhardt, J. A., Zheng, H., Muzikansky, A., Clark, J. W., Kwak, E. L., Schrag, D., Jors, K. R., Fuchs, C. S., Iafrate, A. J., Borger, D. R. and Ryan, D. P. (2011), Phase 1/2 study of everolimus in advanced hepatocellular carcinoma. Cancer, 117: 5094–5102. doi: 10.1002/cncr.26165
- Issue published online: 3 NOV 2011
- Article first published online: 27 APR 2011
- Manuscript Accepted: 3 MAR 2011
- Manuscript Revised: 15 FEB 2011
- Manuscript Received: 22 DEC 2010
- hepatocellular carcinoma;
- mTOR inhibitors;
- clinical trial
The phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway plays a critical role in the pathogenesis of hepatocellular carcinoma (HCC). We performed a single-arm, phase 1/2 study of everolimus in patients with advanced HCC.
Patients with histologically confirmed measurable advanced HCC, 0-2 prior regimens, and adequate hematologic, hepatic, and renal functions received everolimus at 5 mg/day or 10 mg/day orally (6 weeks/cycle). The primary end points were determination of a safe dosage of everolimus (phase 1) and progression-free survival (PFS) at 24 weeks (phase 2).
Twenty-eight patients were enrolled and evaluable for efficacy and toxicity. No dose-limiting toxicities were observed at the 5 mg/day (n = 3) or 10 mg/day (n = 6) dosage level in phase 1. Twenty-five patients received everolimus at 10 mg/day. Grade 3-4 adverse events included lymphopenia (n = 3), aspartate transaminase (n = 3), hyponatremia (n = 2), and 1 patient each with anemia, alanine transaminase, hyperglycemia, proteinuria, rash, and hypoxia. One patient (4%) had partial response (95% confidence interval [CI], 0.9%-19.6%). The median PFS and overall survival were 3.8 months (95% CI, 2.1-4.6) and 8.4 months (95% CI, 3.9-21.1), respectively. The estimated PFS rate at 24 weeks was 28.6% (95% CI, 7.9%-49.3%).
Everolimus was well tolerated in patients with advanced HCC, and 10 mg/day was defined as the phase 2 dosage. Although the study did not proceed to the second stage of phase 2, preliminary antitumor activity was observed with everolimus in patients with advanced HCC, most of whom had prior systemic treatment. Cancer 2011. © 2011 American Cancer Society.