ABSTRACT
BACKGROUND: SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC) via administration into the hepatic artery as a sustained-release suspension in iodized oil. We conducted a multicenter phase II trial in patients with HCC to evaluate the efficacy and safety of SM-11355, using a Zinostatin stimalamer suspension in iodized oil as a reference. METHODS: Patients with unresectable HCC were randomized 2:1 to receive administration of the SM-11355 or Zinostatin stimalamer suspension into the hepatic artery. A second injection was given 4-12 weeks later. Efficacy was evaluated by CT 3 months after treatment and categorized as therapeutic effect (TE) V to I, where TE V was defined as disappearance or 100% necrosis of all treated tumors. RESULTS: A total of 122 patients were evaluated for efficacy and toxicity (SM-11355, n = 83; Zinostatin stimalamer, n = 39). Baseline characteristics were similar in the two groups. The TE V rates were 26.5% (22/83) and 17.9% (7/39) in the SM-11355 and Zinostatin stimalamer groups, respectively. In the SM-11355 group,the most frequent drug-related adverse events (AEs) of ≥ grade 3 were elevated AST, elevated ALT, thrombocytopenia, and hyperbilirubinemia. The AEs with the largest difference between the two groups (SM-11355 vs. Zinostatin stimalamer) were hepatic vascular injury (0 vs. 48.4%) and eosinophilia (84.3 vs. 41.0%). The 2-year and 3-year survival rates were 75.9% vs. 70.3% and 58.4% vs. 48.7%, respectively. CONCLUSIONS: The results suggest that SM-11355 in iodized oil has similar efficacy to Zinostatin stimalamer and that repeated dosing of SM-11355 is possible without hepatic vascular injury in cases of relapse.
Subject(s)
Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Organoplatinum Compounds/administration & dosage , Aged , Carcinoma, Hepatocellular/metabolism , Drug Administration Schedule , Female , Hepatic Artery , Humans , Infusions, Intra-Arterial/methods , Liver Neoplasms/metabolism , Male , Middle Aged , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/pharmacokinetics , Survival RateABSTRACT
BACKGROUND/AIMS: We evaluated patients with nonalcoholic fatty liver disease (NAFLD) and compared the clinical and pathological features to identify the risk factors for NAFLD with severe fibrosis. METHODS: One hundred and eighty-two patients with biopsy-confirmed NAFLD from various medical centres were recruited into this study. RESULTS: The variables that were significantly associated with severe steatosis were male gender (mild:severe=36%:53%, P=0.02), younger age (mild:severe=57%:82%, P>0.001) and absence of type 2 diabetes (mild:severe=43%:71%, P>0.001). There was no significant difference in the degree of inflammation among the clinical groups. The variables that were significantly associated with severe fibrosis were female gender (mild:severe=54%:84%, P=0.002), older age (> or = 60 years old) (mild:severe=29%:53%, P=0.020), type 2 diabetes (mild:severe=42%:71%, P=0.020) and hypertension (mild:severe=24%:53%, P=0.002). Although there were more obese patients in the group with severe fibrosis, the association was not statistically significant (mild:severe=67%:78%, P=0.229). The prevalence of high serum triglyceride levels was similar between the two groups. The N (Nippon) score (total number of risk factor) could significantly predict severe fibrosis in NAFLD patients (1.48 +/- 1.14 vs. 2.66 +/- 0.94, P<0.001). CONCLUSIONS: The N score can be used to predict severe fibrosis in cases of NAFLD.
Subject(s)
Fatty Liver/epidemiology , Fatty Liver/pathology , Liver Cirrhosis/epidemiology , Liver Cirrhosis/pathology , Age Distribution , Aged , Alanine Transaminase/blood , Biopsy, Needle , Disease Progression , Fatty Liver/physiopathology , Female , Humans , Immunohistochemistry , Incidence , Japan/epidemiology , Liver Cirrhosis/physiopathology , Liver Function Tests , Male , Middle Aged , Predictive Value of Tests , Probability , Prognosis , ROC Curve , Retrospective Studies , Risk Assessment , Severity of Illness Index , Sex DistributionABSTRACT
The present study was designed to determine the frequency of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with hepatocellular carcinoma (HCC) in Nagasaki Prefecture, Japan. We examined the clinical features of 1019 patients with HCC who visited our hospitals between January and December 1999. The ratio of men to women was 709 : 310, and the peak incidence of HCC was in the seventh decade of life in both men and women. In the majority of the patients, HCC showed association with HCV infection (74%) compared with HBV infection (17%). HBV-associated HCC was more common in young patients, while HCV-associated HCC was more common in patients with a history as a "daily drinker", or with a history of blood transfusion, liver cirrhosis, and persistently high serum transaminases before the diagnosis of HCC. HCC was initially suspected by ultrasonography or computed tomography in 776 of the 874 patients for whom there was a history of mode of detection of HCC (89%). Tumor size at the time of diagnosis of HCC in patients who had been regularly followed up for liver diseases at our hospitals was significantly smaller than that in patients who were not followed up regularly before the diagnosis ( P < 0.01). Our results indicate that the proportions of patients with HBV or with HCV infection among HCC patients in Nagasaki Prefecture are similar to those found in a nationwide survey in Japan, and there are some differences between the clinical manifestations of HBV- and HCV-associated HCC. Our results emphasize the importance of close follow-up for the high-risk group (i.e. those with HBV- or HCV-associated chronic liver diseases) for the early detection of HCC.
