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Potential of Interferon-α in Solid Tumours

Part 1

  • Therapy Review
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Abstract

Interferon-α (IFNα) is a pleiotropic cytokine with direct and indirect antitumour effects. These include prolongation of the cell cycle time of malignant cells, inhibition of biosynthetic enzymes and apoptosis, interaction with other cytokines, and immunomodulatory and antiangiogenic effects. The first clinical trials in solid tumours used crude preparations of natural IFNα and demonstrated that tumour regressions in solid tumours and haematological malignancies were possible. Since the advent of genetic engineering technology, recombinant (r) IFNα has been widely evaluated in solid tumours. This review discusses the use and potential of rIFNα in solid tumours; the first part focuses on malignant melanoma and metastatic renal cell carcinoma (RCC).

In the adjuvant treatment of malignant melanoma, rIFNα has been tested in randomised trials in more than 6000 patients. High-dosage IFNα (≥10MU) prolongs disease-free survival (DFS) but not overall survival (OS). Low-dosage IFNα (≤3MU) has not been shown to prolong DFS or OS, and current data do not support its use outside clinical trials. The latest United Kingdom Co-ordinating Committee on Cancer Research meta-analysis of ten randomised trials that used adjuvant rIFNα has shown that there is a benefit in DFS but not OS. No conclusions can be reached for intermediate-dosage IFNα (5 to 10MU) until the mature results of the European Organization for Research and Treatment of Cancer (EORTC) study 18952 are available. In RCC, current evidence does not support the use of adjuvant IFNα.

In metastatic malignant melanoma and RCC, reported response rates to rIFNα are approximately 15%. In a minority of responding patients, however, these responses can be long-standing. In metastatic malignant melanoma, IFNα combined with other cytotoxic agents with or without interleukin-2 has achieved high response rates but has not improved survival. In metastatic RCC, intermediate dosages of rIFNα should be used and therapy should probably be prolonged (≥12 months); response depends on prognostic factors such as good performance status, whereas survival is affected by factors such as low tumour burden. Nephrectomy should therefore be considered in patients with good performance status prior to IFNα immunotherapy in advanced RCC, even in patients with metastatic disease.

The toxicity of high-dosage IFNα and the lack of definite benefit on OS with high- or low-dosage IFNα do not support its use outside clinical trials. Data from the ongoing US Intergroup studies, the ongoing EORTC 18991 study (long-term therapy with pegylated IFNα) and mature data from EORTC 18952 (intermediatedosage IFNα) will help establish the role of IFNα as adjuvant therapy in malignant melanoma.

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Acknowledgements

M. Decatris and S. Santhanam contributed equally to this work. No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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  1. Department of Oncology, Leicester Royal Infirmary, Infirmary Square, Leicester, LE1 5WW, UK

    Marios Decatris, Sundar Santhanam & Ken O’Byrne

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  1. Marios Decatris
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  2. Sundar Santhanam
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Correspondence to Marios Decatris.

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Decatris, M., Santhanam, S. & O’Byrne, K. Potential of Interferon-α in Solid Tumours. BioDrugs 16, 261–281 (2002). https://doi.org/10.2165/00063030-200216040-00003

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