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Evaluation of amonafide in disseminated malignant melanoma. A Southwest Oncology Group study
M Slavik1, K J Kopecky, V Sondak
1University of Kansas School of Medicine, Wichita.
Abstract:
Amonafide (AMF), NSC 308847 is an investigational anticancer drug acting as a DNA intercalating agent. This paper presents results of a phase II clinical study of AMF in disseminated malignant melanoma. Twenty patients, eleven males and nine females, with biopsy proven malignant melanoma, performance status 0-2; median age 59 (range 29-74), and no previous chemotherapy, were treated with AMF 300 mg/m2/day by 60 min i.v. infusion for five days repeated every three weeks. Fifteen patients had lung (9 patients) and/or liver (8 patients) involvement. None had known brain metastasis at entry. All 20 patients were evaluated for response and toxicity. Six patients had stable disease and fourteen had increasing disease. With 0/20 responses, the upper 95% confidence limit for the response rate was 14%. The median survival time was 5.7 months. Hematologic toxicity was dose limiting with the incidence of leucopenia 45% and thrombocytopenia 20%. The nonhematologic toxicities included nausea and vomiting (60%), alopecia (20%), headaches (15%), diarrhea (10%), and phlebitis (10%). We conclude that AMF administered at this dose and schedule is not active in the treatment of patients with malignant melanoma, previously untreated with chemotherapy.
Insights
Amonafide (AMF) did not show efficacy in a Phase II trial for advanced melanoma. The investigational DNA intercalating agent demonstrated significant toxicity without achieving treatment responses.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Amonafide (AMF) is an investigational anticancer drug.
- AMF functions as a DNA intercalating agent.
- Malignant melanoma is a significant public health concern.
Purpose of the Study:
- To evaluate the efficacy and toxicity of Amonafide (AMF) in patients with disseminated malignant melanoma.
- To determine the response rate and survival time in this patient population.
Main Methods:
- A Phase II clinical study was conducted.
- Twenty patients with biopsy-proven malignant melanoma received AMF (300 mg/m2/day for five days every three weeks).
- Patients had no prior chemotherapy and performance status 0-2; 15 had lung and/or liver involvement.
Main Results:
- No objective responses were observed in 20 patients (upper 95% confidence limit for response rate was 14%).
- Six patients achieved stable disease; fourteen had progressive disease.
- Median survival time was 5.7 months. Dose-limiting hematologic toxicities included leucopenia (45%) and thrombocytopenia (20%).
Conclusions:
- Amonafide (AMF) at the tested dose and schedule is not active in treating chemotherapy-naive patients with malignant melanoma.
- Significant hematologic and non-hematologic toxicities were observed.
- Further investigation of AMF in this indication is not warranted based on these findings.