[Advanced renal cell carcinoma showing a different response to two types of interferon-alpha]

Interferon (IFN)-alpha has been widely used in systemic therapy for advanced renal cell carcinoma (RCC). IFN-alpha is represented by a large family of structurally related genes expressing at least 14 subtypes, each of which shows quantitatively distinct patterns of biological activities. Although those distinct patterns of biological activities of IFN-alpha subtypes against renal cancer cell lines have been demonstrated, there is no report that demonstrates the difference in each subtype-induced antitumor activity in patients with RCC. Herein, we present a unique case of advanced RCC that is resistant to interleukin-2 and IFN-alpha administration, and we describe its response to another IFN-alpha administration. The difference between the two IFN-alpha types lies in the distribution of the subtypes: this case, therefore, suggests that the difference in the subtype distribution may cause the different response of the RCC. A 47 year-old male was diagnosed as left RCC with multiple lung metastases and underwent radical nephrectomy. The histological diagnosis was pT3b G2 clear cell carcinoma. He received intramuscular administration of 6 x 10(6) units of natural human IFN-alpha (Sumiferon) three times a week following the operation. However, the lung metastases showed progression. Thereafter, he received intravenous administration of 1.4 x 10(6) units of human interleukin-2 everyday. However, the lung metastases showed further progression and the hemoptysis, dyspnea, and chest pain deteriorated. Finally, he was given intramuscular administration of 5 x 10(6) units of another natural human IFN-alpha (OIF) three times a week. After the OIF administration, his complaints subsided and a chest CT scan revealed reduced lung metastases and diminished pleural effusion. He had not received any anti-tumor agents other than IFN-alpha or interleukin-2 since the operation. However, although he remained free of hemoptysis, dyspnea, and chest pain after OIF administration, the lung metastases increased again and multiple brain metastases were also observed five months after the first OIF administration. He died of metastatic RCC one year after the operation.