Key points are not available for this paper at this time.
4120 Background: Patients with unresectable hepatocellular carcinoma (HCC) have a grave prognosis. HCC is a highly vascular tumor with increased levels of angiogenic factors including vascular endothelial growth factors (VEGF). Given the reported activity of gemcitabine (GEM) and oxaliplatin (OX) in HCC and the potential benefits of targeting the VEGF pathway with bevacizumab (B), we performed a phase II study of GEMOX-B in HCC. Methods: Eligibility criteria include unresectable or metastatic measurable HCC, up to two prior chemotherapy regimens, performance status ≤ 1, CLIP score ≤ 3, adequate organ functions, and no clinically significant cardiovascular disease or history of active bleeding. For cycle 1, B is given alone at 10 mg/kg on day 1 (14 day cycle). For cycle 2 and subsequent cycles (28 day cycles), B is given at 10 mg/kg on days 1 and 15, GEM is delivered at 1000 mg/m2 as dose rate infusion at 10 mg/m2/minute followed by OX at 85 mg/m2 on days 2 and 16. CT perfusion scan and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed to assess changes in blood flow and volume. Circulating endothelial cells (CECs) were assayed as a surrogate angiogenesis marker. Results: 27 patients were enrolled: median age = 64 (28–79), M/F = 17/10, ECOG 0/1 = 8/19, CLIP 0/1/2/3=3/8/13/3. The treatment was generally well tolerated. Treatment related grade 3–4 toxicities included (number of patients): transient elevation of transaminases (8), neutropenia (6), nausea/vomiting (2), epistaxis (1), hypertension (1), and thrombocytopenia (1). Two patients had minor responses, five patients had stable disease, and thirteen patients currently remain on study. Twelve patients had more than 50% decrease in the AFP levels during treatment. Decreased blood flow and volume as well as changes in CECs were seen following the B administration alone. Conclusions: GEMOX-B can be safely given with close monitoring in HCC patients with some evidence of antitumor activity. Changes in angiogenic parameters were observed following B administration. Updated information on toxicity, efficacy, and changes in CECs and tumor blood flow correlated with clinical data will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Sanofi
Zhu et al. (Wed,) studied this question.