Interferon-alpha 2a does not improve response or survival when combined with dacarbazine in metastatic malignant melanoma: results of a multi-institutional Australian randomized trial
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D B Thomson1, M Adena, G R McLeod
1Melanoma Clinic, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
Abstract:
Following extensive phase II trials of the combination of dacarbazine and interferon-alpha 2a we performed a prospective, randomized, controlled trial of this combination versus dacarbazine alone as systemic therapy for symptomatic, measurable metastatic malignant melanoma. The two treatment arms were well matched for age, sex, performance, status, relapse-free survival, prior therapy and sites of disease. Therapy consisted of dacarbazine given in combination in escalating doses of 200 mg/m2, 400 mg/m2 and 800 mg/m2 i.v. every 3 weeks, or alone at 800 mg/m2 i.v. every 3 weeks. Interferon was administered subcutaneously starting at 3 mU daily on days 1-3, 9 mU daily on days 4-70, then 9 mU three times per week. Therapy was continued for at least 6 months unless overt progressive disease was observed. Eighty seven patients were randomized to the combination and 83 patients to dacarbazine alone. Response rates were respectively, complete 7% and 2%, and partial 14% and 15%, for a total response rate of 21% (95% confidence limits 13-31%) and 17% (95% confidence limits 10-27%). Median duration of response was 258 and 286 days, and survival of the whole groups 229 and 269 days respectively. Toxicity was worse in the combination arm, with more patients experiencing fatigue, nausea and anorexia, flu-like symptoms and neutropenia. However quality of life was not significantly different in either group, except that fatigue, as measured at week 12 by LASA scales, and activity, as measured by the functional living index, were both improved in the combination.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study found that combining dacarbazine with interferon-alpha 2a for metastatic melanoma showed a slightly higher response rate but increased toxicity compared to dacarbazine alone.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Metastatic malignant melanoma requires effective systemic therapies.
- Combination chemotherapy and immunotherapy are being explored for improved treatment outcomes.
Purpose of the Study:
- To compare the efficacy and toxicity of dacarbazine in combination with interferon-alpha 2a versus dacarbazine alone for metastatic melanoma.
Main Methods:
- A prospective, randomized, controlled trial involving 170 patients with metastatic melanoma.
- Patients received either escalating doses of dacarbazine plus interferon-alpha 2a or dacarbazine alone.
- Treatment continued for at least 6 months or until disease progression.
Main Results:
- Total response rates were 21% for the combination arm and 17% for the dacarbazine-alone arm.
- Median survival was 229 days for the combination arm and 269 days for the dacarbazine-alone arm.
- The combination arm experienced significantly higher toxicity, including fatigue, nausea, anorexia, flu-like symptoms, and neutropenia.
Conclusions:
- While the combination therapy showed a numerically higher response rate, it was associated with increased toxicity.
- Quality of life was not significantly different between the groups, with some improvements noted in activity and fatigue in the combination arm.