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Effect of interferon-alpha 2a on malignant mesothelioma
T I Christmas1, L S Manning, M J Garlepp
1Department of Medicine, University of Western Australia, Nedlands.
Abstract:
Malignant mesothelioma (MM) is a tumor that is resistant to conventional therapy. Interferon-alpha (IFN-alpha) has been used in the treatment of some human tumors, and we have previously demonstrated an in vitro anti-proliferative effect of IFN against MM cell lines. Therefore, the effect of recombinant human IFN-alpha (IFN-alpha 2a) (Roferon-A, Hoffmann-La Roche) on previously untreated patients with MM has been studied. Twenty-five patients (24 male and 1 female), with a mean age of 59 +/- 9.9 years, were treated for 3 months with IFN-alpha 2a. The starting dose was 3 x 10(6) IU daily increasing to a maximum of 18 x 10(6) IU daily or as tolerated. All patients had measurable tumor on thoracic CT prior to commencement. CT scans were performed at 6 and 12 weeks to determine tumor response. Twenty patients completed 3 months of treatment. Five patients were withdrawn because of disease progression. Side effects were predictable and dose related. Dose reductions were necessary in 12 patients for grade 2 toxicity. One patient had a complete response (CR), 2 patients had partial responses (PR) (response rate = 12%), 13 (52%) patients remained stable, 1 of whom exhibited a delayed PR, and 9 (36%) had progressive disease. These data suggest that IFN-alpha 2a is well tolerated in patients with MM and is active against MM in a proportion of patients.
Insights
Recombinant human interferon-alpha 2a (IFN-alpha 2a) showed activity in malignant mesothelioma (MM) patients. This therapy was well-tolerated, with a 12% response rate and 52% stable disease in previously untreated MM.
Area of Science:
- Oncology
- Immunotherapy
Background:
- Malignant mesothelioma (MM) is a challenging cancer resistant to conventional treatments.
- Interferon-alpha (IFN-alpha) has demonstrated anti-proliferative effects against MM cell lines in vitro.
- Recombinant human IFN-alpha 2a (Roferon-A) was investigated for its therapeutic potential in MM.
Purpose of the Study:
- To evaluate the efficacy and safety of IFN-alpha 2a in previously untreated patients with malignant mesothelioma.
- To determine tumor response rates and tolerability of IFN-alpha 2a therapy.
Main Methods:
- A study was conducted on 25 treatment-naive MM patients (24 male, 1 female, mean age 59).
- Patients received IFN-alpha 2a for 3 months, with doses escalating from 3 to 18 million IU daily.
- Tumor response was assessed using thoracic CT scans at 6 and 12 weeks.
Main Results:
- Of 25 patients, 20 completed 3 months of treatment; 5 were withdrawn due to disease progression.
- One complete response (CR) and 2 partial responses (PR) were observed, yielding a 12% overall response rate.
- Thirteen patients (52%) had stable disease, with one showing a delayed PR, and 9 (36%) experienced progressive disease.
- Side effects were dose-related, necessitating dose reductions in 12 patients for grade 2 toxicity.
Conclusions:
- IFN-alpha 2a is a well-tolerated treatment option for malignant mesothelioma.
- The therapy demonstrated clinical activity in a subset of MM patients, including responses and stable disease.
- Further investigation into IFN-alpha 2a's role in MM treatment is warranted.