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Hepatobiliary

Serum -Fetoprotein Response as a Surrogate for Clinical Outcome in Patients Receiving Systemic Therapy for Advanced Hepatocellular Carcinoma

^aDepartment of Medicine, ^bBiostatistics Center, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts, USA; ^cDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA; ^dDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA

Key Words. Carcinoma • Hepatocellular • -fetoprotein • Drug response biomarkers • Clinical trial

Correspondence: Andrew X. Zhu, M.D., Ph.D., Tucker Gosnell Center for Gastrointestinal Cancers, Massachusetts General Hospital Cancer Center, Lawrence House/POB 232, 55 Fruit Street, Boston, Massachusetts 02114, USA. Telephone: 617-643-3415; Fax: 617-724-3166; e-mail: azhu{at}partners.org

Received February 28, 2009; accepted for publication June 2, 2009; first published online in THE ONCOLOGIST Express on July 6, 2009.

Disclosures: Sadhna R. Vora: None; Hui Zheng: None; Zsofia K. Stadler: None; Charles S. Fuchs: None; Andrew X. Zhu: Consultant/advisory role: Bayer, Genentech.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Background. The role of serum -fetoprotein (AFP) as a marker for treatment response in patients with hepatocellular carcinoma (HCC) receiving systemic therapy is poorly defined.

Methods. A retrospective study was performed on patients with advanced HCC enrolled in five phase II clinical trials. Serum AFP was prospectively collected at baseline and at different time points through treatment in parallel with radiologic response and clinical outcome. Patients were separated into three groups based on a 50% change in serum AFP from baseline. Overall survival (OS), progression-free survival (PFS), and radiologic responses were compared between groups using log-rank and Wilcoxon tests.

Results. Of 144 patients, 107 met the eligibility criteria. Eighteen patients experienced a >50% AFP decline, 57 patients had a >50% AFP increase, and 32 patients had a <50% change in serum AFP in either direction. Compared with patients with a <50% change in serum AFP (median PFS, 5.6 months), patients with a >50% AFP decrease had a longer PFS time (median, 16.9 months; p = .029), whereas those with a >50% increase had a shorter PFS time (median, 2.3 months; p = .038). Patients with a >50% rise in AFP had a shorter OS time than those with a <50% change (median, 6.3 months versus 11.1 months, respectively; p = .004), whereas a >50% AFP decrease was not associated with a significant difference in OS (median, 13.0 months; p = .87). AFP changes were significantly associated with radiologic response.

Conclusions. Our study suggests that serum AFP change during treatment may serve as a useful surrogate marker for clinical outcome in patients with advanced HCC receiving systemic therapy.