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A phase II study of pemetrexed in patients with advanced hepatocellular carcinoma

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Pemetrexed has demonstrated activity in hepatocellular carcinoma (HCC) cell lines, and has a manageable toxicity profile in clinical trials, suggesting its potential as a treatment for HCC patients. A multicenter, Phase II community-based study was conducted to assess the response rate and toxicity profile of single-agent pemetrexed in first-line patients with advanced or metastatic HCC. Patients premedicated with folic acid, vitamin B12, and dexamethasone were administered pemetrexed 600 mg/m2 IV on day 1 of each 21-day cycle until disease progression. This nonrandomized study employed Simon’s 2-stage design, enrolling 21 eligible patients in the first stage, stopping accrual if ≤2 responders were observed. Responses were four stable disease, 14 progressive disease, and three not evaluable: two had early toxicities (renal/liver failure, sepsis) and one was noncompliant. The most common grade 3 hematological toxicities were neutropenia 6 of 21 (29%) and thrombocytopenia 3 of 21 (14%); with no grade 4 toxicities. Thirteen patients died on-study: 12 PD and one liver failure; none were drug-related. The median survival was 5.2 months (range, <1–12.2). The planned second stage was cancelled, and the trial was closed owing to lack of response. While pemetrexed was tolerated in this patient population, it was not active.

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We thank the patients who shared their experiences with US Oncology physicians (see Appendix), the site coordinators in the field, project manager Kristy Hyman, and data reviewer Tamara Young who ensured the accuracy and integrity of the data. We thank Jean Kochis, MBA, and Maren K. Levin, MS, for help in writing this manuscript and for their editorial support.

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Correspondence to Allen L. Cohn.

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Research support provided by Eli Lilly and Company, Indianapolis, IN.



The following medical oncologists from the USON network institutions also participated in this study: Carlos A. Alemany, Orlando, FL; Stephen Boswank, Mesquite, TX; Jay G. Courtright, Dallas, TX; Juan Herrada, El Paso, TX; Heidi A. Jordan, Arlington, TX; John F. Kessler, Newport News, VA; Pankaj Khandelwal, Odessa, TX; Darren Kocs, Austin, TX; Kathryn Kolibaba, Vancouver, WA; Henry K. Lee, Phoenix, AZ; Andrew D. McCollum, Dallas, TX; Michael Roberts, Phoenix, AZ; John Sandbach, Austin, TX.

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Cohn, A.L., Myers, J.W., Mamus, S. et al. A phase II study of pemetrexed in patients with advanced hepatocellular carcinoma. Invest New Drugs 26, 381–386 (2008).

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