Multi-modal treatment of primarily using continuous subcutaneous interferon-α injection in combination with surgery and/or radiotherapy

PURPOSE: Thirty-nine renal cell carcinoma patients with bony metastasis were intensively treated, primarily with immunotherapy using natural type interferon-alpha (IFN-alpha) continuous subcutaneous injection in combination with surgical resection and radiation therapy. Long-term survival was achieved, including three patients with complete response. The results of this study are presented. METHODS: The mode of administration of IFN-alpha was as follows: natural-type IFN-alpha (25,000,000 IU) was dissolved in 60 mL of distilled water and administered via continuous subcutaneous injection (0.5 mL/h) as 'one course of the treatment'. Two courses of IFN-alpha therapy were given 2 weeks preoperatively, while 13 courses of IFN-alpha therapy were given postoperatively (one course per week). Thus, 15 courses of IFN-alpha therapy were administered during the trial period. Thereafter, IFN-alpha therapy was repeated either every week or every other week depending on the condition of the patient. Additionally, blood levels of IFN-alpha were monitored for four patients following initiation of IFN-alpha continuous subcutaneous injection therapy. RESULTS: Immediately after injection of IFN-alpha, blood levels of IFN-alpha started to rise, reaching 40.5 IU/mL on average at 24 h after initiation of IFN-alpha therapy. Thereafter, blood levels of IFN-alpha remained high and measurable blood levels of IFN-alpha were maintained for up to 24 h after completion of IFN-alpha injection. As a whole, IFN-alpha was detectable for 6-8 days and Cmax (maximum blood concentration of IFN) was 167 IU/mL. Thirty-nine patients with bony metastases were treated as follows: IFN mono-therapy (19 patients), IFN and radiation therapy (15 patients) and IFN and surgical resection of bony metastases (five patients). Fourteen patients survived and the details of these 14 patients are as follows: complete response in three cases, partial response in two, no change in six and progressive disease in three. Twenty-five patients died of renal cell carcinoma. The overall 5-year survival rate was 35.0%. CONCLUSIONS: These findings indicate that IFN-alpha continuous subcutaneous injection therapy is a useful modality for renal cell carcinoma patients with bony metastasis if administered in combination of radical nephrectomy and radiation therapy.