The mean total bilirubin for the entire group did not change from www.selleckchem.com/epigenetic-reader-domain.html baseline (0.68 mg/dl) to 1 month (0.68 mg/dl). However, at 3 and 6 months after TARE, the mean bilirubin of the group was higher at 0.95 mg/dl and 1.05 mg/dl, respectively. A clinically significant increase defined as a rise above 1.2 mg/dl was only seen in two patients at 3 and 6 months. In these patients, the rise in bilirubin was associated with

an increased burden of disease. Absolute neutrophil or lymphocyte count did not substantially change from baseline to 1 month or 3 months after treatment. No patient developed neutropenia defined as a neutrophil count of less than 1500 per microliter. Clinically, two patients developed worsening ascites following treatment requiring hospitalization and/or intervention. It is unclear if their ascites were directly related to treatment or tumor progression. No variceal bleeding or encephalopathy was seen following treatment. One patient developed a duodenal ulcer months after TARE which

was attributed to antiangiogenic therapy. For all patients, median survival from the time of gemcitabine plus TARE was 12.3 months, and the time to local failure, defined as progression in the region targeted by TARE, was 7.1 months. In the five patients with liver-confined HCC there were one complete response, three partial responses, one patient with stable disease, and one patient with no response/progressive disease after treatment (Figure 4). Median time to local failure was 9.9 months and overall survival was 12.5 months Z VAD FMK for the patients with HCC. The eight patients treated for liver metastases had a median Sucrase survival of 9.2 months and time to local failure of 6.4 months (Table 2). Overall, these findings suggest

that radiosensitizing doses of gemcitabine can be combined with 90Y microspheres in patients with HCC and liver metastases. Despite the proven benefit of adding chemotherapy to radiation in most GI malignancies, combining chemotherapy with 90Y microspheres for HCC has not been previously studied. In the current study, we found that gemcitabine and 5-FU were effective radiosensitizing agents at noncytotoxic and clinically achievable concentrations in HCC cell lines treated with LDR (0.07–0.26 Gy/h). Interestingly, the level of radiosensitization with LDR was greater than what was observed in cells treated with SDR (2 Gy/min) under otherwise similar conditions. Sorafenib produced radiosensitization when administered after LDR; however, the doses required to radiosensitize were above a concentration which is achievable in patients. Given these results, gemcitabine and 5-FU are promising agents to combine with 90Y microspheres, whereas sorafenib may not produce more than an additive effect at clinically relevant concentrations. Gemcitabine and 5-FU are antimetabolites with different mechanisms of action.