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Published on: January 25, 2015
Safety and efficacy of arsenic trioxide for patients with advanced metastatic melanoma
Ahmad A Tarhini1, John M Kirkwood, Hussein Tawbi
1Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Background:
Arsenic trioxide (ATO) cytotoxicity and apoptosis induction has been demonstrated with numerous cancer cell lines, including human melanoma.
Methods:
A second-line, phase 2, single-arm 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.
Results:
Twenty-one 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-related 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], 0-29%) 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, 11-38 weeks) and the median survival was 13 months (95% CI, 12-26 months).
Conclusions:
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.
Insights
Arsenic trioxide (ATO) showed limited activity in patients with stage IV melanoma, with one partial response and disease stabilization in 59%. While well-tolerated, further research combining ATO with other therapies is needed.
Area of Science:
- Oncology
- Melanoma Research
- Cancer Therapeutics
Background:
- Arsenic trioxide (ATO) is known to induce cytotoxicity and apoptosis in various cancer cell lines, including human melanoma.
- Metastatic melanoma remains a significant challenge, necessitating exploration of novel therapeutic agents.
Purpose of the Study:
- To evaluate the efficacy and safety of arsenic trioxide (ATO) as a second-line treatment for patients with inoperable stage IV melanoma.
- To determine the response rate, disease stabilization, time to progression, and overall survival in this patient cohort.
Main Methods:
- A phase 2, single-arm study involving patients with inoperable American Joint Committee on Cancer (AJCC) stage IV melanoma.
- Patients received a specific dosing regimen of ATO over multiple weeks, followed by response assessment.
Main Results:
- Twenty-one patients with stage IV melanoma were enrolled; 17 were evaluable for response.
- One patient (6%) achieved a partial response, and 10 patients (59%) had disease stabilization, though all eventually progressed.
- Median time to progression was 17 weeks, and median survival was 13 months. Toxicities were generally manageable.
Conclusions:
- Arsenic trioxide (ATO) was well-tolerated but demonstrated limited activity as a single agent in patients with metastatic melanoma.
- Combination therapy with chemotherapy or targeted agents warrants investigation to enhance efficacy in melanoma treatment.
