Single-agent pemetrexed in patients with advanced and metastatic hepatoma

Abstract

14064 Background: The incidence of hepatoma is rising in the United States, primarily due to the increase in the prevalence of hepatitis C. Surgical treatments are rarely an option for patients with advanced hepatoma, and while chemotherapy, particularly with doxorubicin-based regimens, has marginally prolonged survival, response rates have been poor with the burden of high toxicity. Pemetrexed, a folate antimetabolite, has demonstrated activity in hepatoma cell lines with a manageable toxicity profile, making it a potentially useful agent in hepatocellular carcinoma. Methods: A multicenter, Phase II study was conducted to assess the response rate and evaluate the toxicity profile of single-agent pemetrexed (ALIMTA) in first-line patients with advanced or metastatic hepatoma. Pemetrexed 600 mg/m2 IV was administered on Day 1 of each 21-day cycle until disease progression (PD). Patients were premedicated with dexamethasone 4 mg PO BID and received daily folic acid 350–1000 μg PO and Vitamin B12 1000 μg IM every 9 weeks. Results: This nonrandomized study employed Simon’s 2-stage design. There were 21 eligible patients enrolled in the first stage, and all 21 patients were enrolled within 4 months of trial opening. Median age was 72 years (range, 44–88), and most patients were white (62%) and male (81%). Ten percent (10%) had an ECOG PS of 2, 48% Stage IV disease, 52% prior surgery, and 33% tumors of unknown histological grade. The plan was to stop accrual if ≤2 responders were observed among the 21 patients. Of the 21 patients, 3 had SD, 2 had early toxicities (renal/liver failure, sepsis), 15 progressed, and 1 was noncompliant. The trial was closed due to lack of response. The most common Grade 3 hematological toxicities were neutropenia 6/21 (28.6%) and thrombocytopenia 3/21 (14.3%). One patient experienced both Grade 3 nausea and vomiting. There were no Grade 4 toxicities. There were 10 on-study deaths: 9 PD and 1 liver failure. None of the deaths were drug-related. The median actual survival was 2.5 months (range, <1–8). Conclusions: While pemetrexed was well tolerated in this patient population, it was not active. Most adverse events were related to disease state, not study treatment. Supported by Eli Lilly and Company, Indianapolis, IN [Table: see text]