The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Design and Endpoints of Clinical Trials in Hepatocellular Carcinoma
Open accessAbstract
The design of clinical trials in hepatocellular carcinoma (HCC) is complex because many patients have concurrent liver disease, which can confound the assessment of clinical benefit. There is an urgent need for high-quality trials in this disease. An expert panel was convened by the American Association for the Study of Liver Diseases to develop guidelines that provide a common framework for designing trials to facilitate comparability of results. According to these guidelines, randomized phase 2 trials with a time-to-event primary endpoint, such as time to progression, are pivotal in clinical research on HCC. Survival remains the main endpoint to measure effectiveness in phase 3 studies, whereas time to recurrence is proposed as an appropriate endpoint in the adjuvant setting. Because progression-free survival and disease-free survival are composite endpoints, they are more vulnerable than others in HCC clinical studies and may not be able to capture clinical benefits. Selection of the target population should be based on the Barcelona Clinic Liver Cancer staging system. New drugs should be tested in patients with well-preserved liver function (Child-Pugh A class). Patients assigned to the control arm should receive standard-of-care therapy, that is, chemoembolization for patients with intermediate-stage disease and sorafenib for patients with advanced-stage disease. Further research is needed to incorporate biomarkers and molecular imaging into clinical research in HCC. These surrogate markers may help to enrich study populations and maximize the cost-benefit ratio of trial execution. Design and conduct of phase 3 trials should be coordinated by centers with appropriate expertise in HCC.
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Cites
Assessing the quality of reports of randomized clinical trials: Is blinding necessary?
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Sorafenib in advanced hepatocellular carcinoma
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Cited by
Sorafenib in advanced hepatocellular carcinoma
Llovet, J. M., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Blanc, J.-F., de Oliveira, A. C., Santoro, A., Raoul, J.-L., Forner, A., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0708857 · Cited by 13,097
Self-citationEASL Clinical Practice Guidelines: Management of hepatocellular carcinoma
Galle, P. R., Forner, A., Llovet, J. M., Mazzaferro, V., Piscaglia, F., Raoul, J.-L., Schirmacher, P., & Vilgrain, V. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.03.019 · Cited by 11,406
Self-citationEASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma
European Association for the Study of the Liver, & European Organisation for Research and Treatment of Cancer (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2011.12.001 · Cited by 5,218
“In this regard, the seminal classification reported in 1999 [148] was updated with the incorporation of stage 0 (very early HCC) and chemoembolization for intermediate HCC in 2003 [99], and further modified in 2008 to incorporate sorafenib as first-line treatment option in advanced tumors [149].”
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Self-citationGene expression in fixed tissues and outcome in hepatocellular carcinoma
Hoshida, Y., Villanueva, A., Kobayashi, M., Peix, J., Chiang, D. Y., Camargo, A., Gupta, S., Moore, J., Wrobel, M. J., Lerner, J., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804525 · Cited by 1,286
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Metadata
- Authors
- Llovet, J. M., Di Bisceglie, A. M., Bruix, J., Kramer, B. S., Lencioni, R., Zhu, A. X., Sherman, M., Schwartz, M., Lotze, M., Talwalkar, J., Gores, G. J., & Trials, F. T. P. O. E. I. H.-D. C.
- Venue
- JNCI: Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-05-21
- Volume
- 100
- Issue
- 10
- Pages
- 698-711
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2153935627
- Cited by
- 1,653
- References
- 8
- FWCI
- 81.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Llovet, J. M., Di Bisceglie, A. M., Bruix, J., Kramer, B. S., Lencioni, R., Zhu, A. X., Sherman, M., Schwartz, M., Lotze, M., Talwalkar, J., Gores, G. J., & Trials, F. T. P. O. E. I. H.-D. C. (2008). Design and Endpoints of Clinical Trials in Hepatocellular Carcinoma. JNCI: Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/djn134
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
