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Updated: Jun 12, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
A phase 1-2 study of imexon plus dacarbazine in patients with unresectable metastatic melanoma
Jeffrey S Weber1, Wolfram E Samlowski, Rene Gonzalez
1Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida 33612, USA. Jeffrey.weber@moffitt.org
Background:
Imexon (Amplimexon) is an aziridine compound that increases reactive oxygen species, disrupts mitochondrial membranes, and induces apoptosis. Preclinical studies showed activity against melanoma cell lines and models in mice, and synergy with dacarbazine. The authors evaluated standard doses of dacarbazine combined with increasing doses of imexon to determine the maximal tolerated dose (MTD), toxicities, pharmacokinetics, and efficacy.
Methods:
Sixty-eight chemotherapy-naive melanoma patients (1 inoperable stage III and 67 stage IV) were treated with dacarbazine (250 mg/m2) and imexon (570-1300 mg/m2), both daily for 5 days every 3 weeks.
Results:
There were 18 patients in the phase 1, and 50 in the phase 2 component of the study. The MTD of imexon with dacarbazine was 1000 mg/m2. Dose-limiting toxicities were pulmonary edema and hepatorenal failure. At the MTD, therapy was well tolerated. The most common toxicities (any grade) were vomiting, diarrhea, anemia, thrombocytopenia, anorexia, fever, and constipation. Among 68 patients, there were 7 treatment-related serious adverse events. Partial response and stable disease rates were 5.9% and 25% for all subjects and 2% and 30% for the phase 2 patients, respectively. Median progression-free and overall survival of all patients were 2.0 and 11.7 months and 2 and 7.5 months for the phase 2 patients, respectively. Overall survival of the 31 patients with normal lactate dehydrogenase levels was >22.5 months. Pharmacokinetics of both drugs were similar to previous reports.
Conclusions:
Imexon plus dacarbazine was well tolerated. The survival data suggest further evaluation in a randomized phase 2 study.
Insights
The combination of imexon and dacarbazine showed promising survival outcomes in melanoma patients. Further randomized trials are recommended to confirm the efficacy of this imexon (Amplimexon) and dacarbazine regimen.
Area of Science:
- Oncology
- Pharmacology
Background:
- Imexon (Amplimexon) is an aziridine compound with demonstrated preclinical activity against melanoma.
- Imexon increases reactive oxygen species, disrupts mitochondrial membranes, and induces apoptosis.
- Preclinical studies indicated synergy between imexon and dacarbazine.
Purpose of the Study:
- To determine the maximal tolerated dose (MTD) of imexon in combination with dacarbazine.
- To evaluate the toxicities, pharmacokinetics, and efficacy of this combination therapy.
- To assess the safety and tolerability of escalating imexon doses.
Main Methods:
- A phase 1/2 study involving 68 chemotherapy-naive melanoma patients (stage III and IV).
- Patients received standard dacarbazine (250 mg/m2) with escalating doses of imexon (570-1300 mg/m2) for 5 days every 3 weeks.
- The MTD was determined, and toxicities, response rates, and survival were assessed.
Main Results:
- The MTD of imexon with dacarbazine was established at 1000 mg/m2.
- Dose-limiting toxicities included pulmonary edema and hepatorenal failure; however, therapy was well tolerated at the MTD.
- Partial response and stable disease rates were observed, with significantly longer overall survival (>22.5 months) in patients with normal lactate dehydrogenase levels.
Conclusions:
- Imexon in combination with dacarbazine was found to be well tolerated in melanoma patients.
- The observed survival data warrant further investigation in a randomized phase 2 study.
- This combination therapy shows potential as a treatment option for advanced melanoma.
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