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Background The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. Patients and methods Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. Results Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2–34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2–30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89–9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62–9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74–1.36). The response rates were 49.1% (95% CI 39.7–58.6) and 45.9% (95% CI 36.4–55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%). Conclusion No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity. Clinical Trial Number NCT00851084, www.clinicaltrials.gov , EudraCT 2008-004178-41.

PURPOSE Analysis of the course of disease in patients with histologically proven HCC before and after orthotopic liver transplantation (LTx) who received transarterial chemoembolization (TACE). MATERIAL AND METHODS Thirty-five of a total collective of 363 patients with histologically proven HCC underwent LTx. Before LTx, all patients were treated with sequential TACE. According to treatment pattern, TACE should be performed every 6 weeks, using a suspension consisting of max. 10 mg Mitomycin C as well as 10 - 30 ml iodized oil (Lipiodol). Patients were classified according to the Milano criteria. Criteria were called exceeded if the tumor size was > 5 cm and/or > 3 tumors larger than 3 cm were found. Therapy success and liver function were examined by means of spiral CT and laboratory controls. Investigation parameters included the number of tumor knots as well as the maximum tumor size. Additionally, the Lipiodol accumulation, the patency of the portal vein and the occurrence of complications were checked. RESULTS Altogether, 184 TACE procedures were accomplished (5.3 +/- 3.3, range 1 - 14). The waiting period up to the transplantation amounted to 366 +/- 255 days (range 44 - 1137). The average number of tumor knots for each patient was 3.1 +/- 2.2 before and 2.9 +/- 2.2 after TACE (p = 0.887). The average tumor size was 4.2 +/- 2.5 before and 2.8 +/- 1.4 after TACE. The Milano criteria to LTx crossed 17/35 patients. Patients with exceeded Milan criteria showed a highly significant size reduction of the tumor after TACE (p = 0.001); in 9/17 cases the transplantation criteria were secondarily fulfilled through downstaging. A successful LTx was accomplished in 35/35 cases. Follow up after LTx was 769 +/- 509 days. The tumor recurrence in patients with exceeded vs. fulfilled transplantation criteria was 11.1 % vs. 11.8 % (p = 0.99). The recurrence free survival was 93.3 %, 82.5 % and 82.5 % at 1, 3 and 5 years, respectively. There were no relevant differences between patients with exceeded vs. fulfilled transplantation criteria (p = 0.99). CONCLUSION The sequential TACE is an effective method for the therapy of the HCC before LTx in selected patients. A relevant downsizing could be achieved by TACE in patients with advanced HCC. Patients with larger tumors showed a significantly stronger size reduction after TACE. The recurrence rate and the survival rate for patients with advanced or small tumors do not differ.

More than 90% of patients with genetic hemochromatosis carry a characteristic mutation in the HFE-gene (C282Y). HFE modulates the iron uptake by the transferrin receptor. Duodenal crypt cells of HFE-knockout mice show low intracellular iron concentrations which lead to an upregulation of the divalent metal transporter and enhanced iron uptake by duodenal enterocytes. Heterozygosity for the C282Y mutation appears to alter the course of other liver diseases like porphyria cutanea tarda and nonalcoholic steatohepatitis.