Local hyperthermia and systemic chemotherapy for treatment of recurrent melanoma.

Thirty-two patients with recurrent (skin) or metastatic (skin, node, or both) melanoma have been treated with a hyperthermia-cisplatin regimen. The hyperthermic treatment was carried out for 60 minutes at 43 degrees C with the MHS-SMA and the Sapic SVO3 ALENIA devices once a week. When the tumor temperature reached 42 degrees C, cisplatin was administered at a dosage of 50 mg/m2 given by intravenous bolus infusion. The treatment was repeated four times and the tumor response evaluated 4 weeks after the last treatment. Significant systemic or local toxicity was not seen. In terms of results, there were 9 patients with complete responses (28.1%), 13 with partial responses (40.6%), 8 with no change (25.0%), and two with disease progression (6.3%). The objective response rate was 68.7%. The response duration for those with complete responses ranged from 4 to 49 months (median 20 months). The median time to progression for patients with partial responses and those with no change was 6 and 5 months, respectively, with ranges of 1-7 and 1-10 months, respectively. The 4-year actuarial survival rates were 47.6% and 20.3% for the complete and incomplete responders, respectively. These results can be considered satisfactory, taking into account that most patients were pretreated with radiotherapy, chemotherapy or both, confirming the therapeutic potential of the hyperthermia and cisplatin regimen

Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects.

BACKGROUND: The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. METHODS: We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). RESULTS: The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. CONCLUSIONS: Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.