TY - JOUR
T1 - A phase II study of bortezomib in the treatment of metastatic malignant melanoma
AU - Markovic, Svetomir N.
AU - Geyer, Susan M.
AU - Dawkins, Fitzroy
AU - Sharfman, William
AU - Albertini, Mark
AU - Maples, William
AU - Fracasso, Paula M.
AU - Fitch, Tom
AU - LoRusso, Patricia
AU - Adjei, Alex A.
AU - Erlichman, Charles
PY - 2005/6/15
Y1 - 2005/6/15
N2 - BACKGROUND. Bortezomib 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. METHODS. Patients 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 a 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. RESULTS. The 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 1:0 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. CONCLUSIONS. Single-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.
AB - BACKGROUND. Bortezomib 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. METHODS. Patients 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 a 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. RESULTS. The 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 1:0 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. CONCLUSIONS. Single-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.
KW - Bortezomib
KW - General
KW - Metastatic malignant melanoma
KW - Proteosome inhibitor
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U2 - 10.1002/cncr.21108
DO - 10.1002/cncr.21108
M3 - Article
C2 - 15887220
AN - SCOPUS:20444364475
SN - 0008-543X
VL - 103
SP - 2584
EP - 2589
JO - Cancer
JF - Cancer
IS - 12
ER -