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BACKGROUNDBortezomib is a proteasome inhibitor with manageable clinical toxicity and laboratory evidence of anti‐melanoma activity. Therefore, it was considered for clinical testing in patients with metastatic melanoma.METHODSPatients with metastatic melanoma and adequate hematologic, renal, and hepatic function were treated with bortezomib (a 1.5‐mg/m2 intravenous bolus twice weekly for 2 of every 3 weeks). Eligible patients were age ≥ 18 years with an Eastern Cooperative Oncology Group performance status of 0–1. The primary goal of the current study was to evaluate the 18‐week disease progression‐free survival rate and tolerability of bortezomib in these patients.RESULTSThe current study was intended to treat 45 patients. It was closed at the planned interim analysis due to early evidence of insufficient clinical efficacy. Twenty‐seven patients with a median age of 56 years (range, 32–77 years)were accrued. There were no major clinical responses to treatment. Only 6 patients (22%) achieved stable disease. Of these 6 patients, 4 were still stable after 4 cycles of treatment, but were removed from the study due to toxicity. The median time to disease progression was 1.5 months (95% confidence interval [95% CI], 1.4–1.6) with a median overall survival of 14.5 months (95% CI, 9–22). Having failed bortezomib, most patients proceeded to other clinical trials. Twenty‐six patients were evaluable for toxicity. One patient was removed from the study for other reasons and could not return for the cycle evaluation and thus was never evaluated. Of the 26 patients, no Grade 4/5 treatment‐related toxicities (using the National Cancer Institute Common Toxicity Criteria [version 2.0]) were reported. Eleven patients (42%) had Grade 3 toxicities (believed to be at least possibly related to treatment), including sensory neuropathy, thrombocytopenia, constipation, fatigue, ileus, abdominal pain, and infection without neutropenia. The median number of treatment cycles patients received was two (range, one to six treatment cycles). Two patients (7%) had 1 dose delay and 6 patients (22%) had dose reductions during 1 treatment cycle due to adverse events.CONCLUSIONSSingle‐agent bortezomib, administered twice weekly × 2 weeks, every 3 weeks at a dose of 1.5 mg/m2, was not found to be effective in the treatment of patients with metastatic melanoma. Cancer 2005. © 2005 American Cancer Society.

Cholelithiasis is considered an extraintestinal manifestation of Crohn's ileitis but has not been associated with ulcerative colitis. To evaluate if an increased risk of cholelithiasis exists in patients with ulcerative colitis, biliary ultrasonography was performed on 159 patients with inflammatory bowel disease, 114 patients with ulcerative colitis, and 45 patients with Crohn's disease. A control population of 2453 residents of the town near the authors' institute was also studied. An echographic survey of gallstones was performed on the control subjects, who participated in the Multicentrica Italiana Colelitiasi (MICOL). Seventeen patients with inflammatory bowel disease had gallstones (10.7 percent), 11 patients with ulcerative colitis had gallstones (9.6 percent), and 6 patients with Crohn's disease had gallstones (13.3 percent). In the control population, diagnosis of cholelithiasis was made in 239 subjects (9.7 percent). An estimate of the relative risk (odds ratio) of gallstones in ulcerative colitis and Crohn's disease and also in 4 subgroups formed on the basis of the extent of disease (total ulcerative colitis, partial ulcerative colitis, Crohn's disease with ileitis, Crohn's disease without ileitis) with respect to the general population was calculated using logistic regression with gallstones, sex, age, and body mass index as independent variables and inflammatory bowel disease as a dependent variable. The author's findings show an increased risk of gallstones in both patients with Crohn's disease (odds ratio = 3.6; 95 percent confidence limits = 1.2 - 10.4; P = 0.02) and patients with ulcerative colitis (odds ratio = 2.5; 95 percent confidence limits = 1.2 - 5.2; P = 0.01). The risk was highest in patients with Crohn's disease involving the distal ileum (odds ratio = 4.5; 95 percent confidence limits = 1.5 - 14.1; P = 0.009) and in patients with total ulcerative colitis extending to the cecum (odds ratio = 3.3; 95 percent confidence limits = 1.3 - 8.6; P = 0.01). These results confirm that there is an increased risk of gallstones in Crohn's ileitis but they show that there also exists an increased risk in patients with total ulcerative colitis.

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