Practical Effect of Sorafenib Monotherapy on Advanced Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis

BACKGROUND/AIMS: We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting. METHODS: In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. RESULTS: All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. CONCLUSIONS: A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.

Anorexic effect of (R)-sibutramine: comparison with (RS)-sibutramine [corrected] and (S)-sibutramine.

Sibutramine is one of the very few drugs that are approved for long-term treatment of obesity. Sibutramine is a racemic mixture (RS) containing two equal forms of the R(+) and S(-) enantiomers. In this paper, we have investigated comparative anorexic effect of sibutramine enantiomers and their recemate form in rats. After obtaining two days of baseline results, rats were administered orally either with (RS)-sibutramine or its enantiomers (R)- or (S)-sibutramine at dose levels of 5, 10, 20 mg/kg each for 4 days and body weight, food intake and water intake were measured daily. Locomotor activity score of each rat was also recorded on each day. R-Sibutramine and (RS)-sibutramine produced dose dependant decrease in the body weight and food intake. On the other hand, (S)-sibutramine was shown to increase in these parameters. Neither sibutramine nor it's enantiomers showed any consistent effects on spontaneous motor activity (SMA) scores. In conclusion, (R)-sibutramine is better anorexic than or (RS)-sibutramine or it's (S)-enantiomers.

Efficacy of sulphasalazine plus methotrexate in rheumatoid arthritis.

Early intervention with slow acting anti-rheumatic drugs (SAARDs) has led to improvement in substantial proportion of rheumatoid arthritis (RA) patients. The present open, controlled study was designed to assess whether a combination of SAARDs offer any added benefit. Fifty-four adult RA patients were randomly allocated to methotrexate (MTX) (n = 27) and MTX plus sulphasalazine (SSZ) (n = 27) groups. The subjects were followed-up fortnightly for four weeks then monthly for six months. The disease activity was assessed with the help of 10 clinical and four laboratory indices. The improvement was graded as: minor, mild decreases in indices, non-steroidal anti-inflammatory drugs (NSAIDs) continued, physician's global assessment (PGA) decreased by one; marked, acceptable decreases in indices, NSAIDs being taken sparingly, PGA decreased by at least 2, and complete, all indices normalised and patients discontinued NSAIDs completely. The improvement was considered clinically important when marked or complete improvement occurred. Adverse drug reactions resulted in withdrawal of 4 subjects from the MTX + SSZ group and 1 from the control groups. Four and three subjects in the combined and MTX groups respectively were lost to follow-up. Subjects in both groups showed significant decline in all indices except hemoglobin and neutrophil count. The differences between the two groups in the pre-treatment and post-treatment values were insignificant. Complete, marked, minor and no improvement occurred in 4 (21%), 12 (63%), 3 (16%) & 0 in the MTX and in 11 (48%), 7 (30%), 4 (17%) & 1 (4%) in MTX + SSZ groups respectively. The differences in the rates of complete and clinically important improvement between the two groups were insignificant (P 0.1398 and 0.7092). The incidence of side effects was insignificantly higher in the MTX + SSZ group. Most of them were mild and transient. The combination of SAARDs offered little added advantage in RA. However, the higher rate of complete improvement in the combination group justifies trials including larger samples.

Ascorbic acid delays the development of tolerance to amphetamine induced anorexia but does not affect the reverse tolerance which develops to the locomotor activity.

Ascorbic acid (1 g/kg) accentuated anorectic and locomotor effects of amphetamine (5 mg/kg) and delayed development of tolerance to anorectic effect. On the contrary, it did not alter the pattern of reverse tolerance to increased locomotor activity. The results suggest that modulation of dopamine receptor sensitivity by ascorbic acid may be the reason for the delay in development of tolerance to amphetamine induced anorexia.

Effect of lead on anorexia and body weight in albino rats.

Rats exposed to lead (lead acetate) in doses of 0.2 and 0.5 mg/ml in drinking water for a period of 90 days showed mild to moderate changes in food consumption compared to control group. Drug interactions in lead exposed rats with metoclopramide, atropine sulphate, propranolol, cyproheptadine and mepyramine maleate when administered intraperitoneally caused -30 to +30 percentage variation in food intake indicating the influence of adrenergic, serotonergic and cholinergic neurotransmitters with no change in mean body weight of lead treated rats.

Influence of prior information of drug toxicity on patient compliance.

Sixty patients with pulmonary tuberculosis, who had not received any chemotherapy in the past, were divided into two groups. All the patients were put on isoniazid, rifampicin and pyrazinamide for 8 weeks followed by isoniazid and rifampicin for another 18 weeks. Group A patients were informed of the likely occurrence of anorexia and/or vomiting but Group B patients were not. Routine and default retrieval home visits were given to ensure maximal drug compliance. Drug toxicity related early defaults were significantly less common in Group A patients (1 of 30) as compared to Group B (6 of 30).