{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T07:26:21Z","timestamp":1763105181669,"version":"build-2065373602"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,1,18]],"date-time":"2008-01-18T00:00:00Z","timestamp":1200614400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND.<\/jats:title><jats:p>Arsenic trioxide (ATO) cytotoxicity and apoptosis induction has been demonstrated with numerous cancer cell lines, including human melanoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS.<\/jats:title><jats:p>A second\u2010line, phase 2, single\u2010arm study of ATO was conducted in patients with inoperable American Joint Committee on Cancer (AJCC) stage IV melanoma. One cycle consisted of a loading dose of 0.32 mg\/kg\/day for 4 days in Week 1, followed by 0.25 mg\/kg\/day twice per week for 6 weeks, followed by 1 week of rest, at which time response assessment was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS.<\/jats:title><jats:p>Twenty\u2010one patients (median age, 63.8 years) were accrued. All had stage IV melanoma including M1a (2 patients), M1b (6 patients), and M1c (13 patients) disease. One patient had metastatic choroidal melanoma and 20 patients had cutaneous melanoma. Twenty patients had received prior therapy. Possible treatment\u2010related grade 3 of 4 toxicities (using the National Cancer Institute Common Toxicity Criteria) included 1 case of idiopathic thrombocytopenic purpura and 1 case of elevated lactate dehydrogenase. Four patients did not complete the first cycle of therapy and were not evaluable for response. Among 17 evaluable patients, 1 patient (6%; 95% confidence interval [95% CI], 0\u201329%) achieved a partial response lasting 7 months, and 10 patients (59%) had disease stabilization after at least 1 cycle, but all eventually developed disease progression. The median time to disease progression was 17 weeks (95% CI, 11\u201338 weeks) and the median survival was 13 months (95% CI, 12\u201326 months).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS.<\/jats:title><jats:p>ATO as tested in the current trial was found to be well tolerated and had limited activity in patients with metastatic melanoma. The application of this agent in combination with either chemotherapy or agents that target recognized critical signaling and antiapoptotic pathways of melanoma has not yet been performed. 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