Clinical outcome of combined immunotherapy with low-dose interleukin-2 and interferon-α for Japanese patients with metastatic renal cell carcinoma who had undergone radical nephrectomy: a preliminary report

Abstract

Our preliminary experience suggests that long-term, repeated treatment with IFN-alpha and low-dose IL-2 is feasible in Japanese patients with metastatic RCC who have undergone radical nephrectomy. Although it will be necessary to accumulate data from a larger number of patients with a longer follow-up period, the combined immunotherapy tested in this study may become the preferred therapy for Japanese patients with metastatic RCC.

Prediction of response to combined immunotherapy with interferon‐α and low‐dose interleukin‐2 in metastatic renal cell carcinoma: Expression patterns of potential molecular markers in radical nephrectomy specimens

“…Although among various kinds of immunotherapy, high‐dose bolus IL‐2 is the only agent approved by the US Food and Drug Administration for the treatment of advanced RCC, 15 we have chosen to perform combined immunotherapy with IFN‐α and low‐dose IL‐2 as a primary treatment for patients with metastatic RCC in order to maintain the clinical efficacy of high‐dose IL‐2 while avoiding its extremely severe toxicity 6 . However, several problems associated with this combined regimen have also been identified, such as an unfavorable response rate, high incidence of adverse events and expensive medical cost.…”

“…Although among various kinds of immunotherapy, high-dose bolus IL-2 is the only agent approved by the US Food and Drug Administration for the treatment of advanced RCC, 15 we have chosen to perform combined immunotherapy with IFN-a and low-dose IL-2 as a primary treatment for patients with metastatic RCC in order to maintain the clinical efficacy of high-dose IL-2 while avoiding its extremely severe toxicity. 6 However, several problems associated with this combined regimen have also been identified , such as an unfavorable response rate, high incidence of adverse events and expensive medical cost. Considering these findings, it should be performed only in selected patients who will be likely to have therapeutic benefits from this combined therapy; therefore, in the present study, we evaluated the association of several conventional clinicopathological factors as well as multiple potential molecular markers in primary clear cell RCC specimens with response to this regimen for the development of a useful system predicting clinical outcomes in patients with metastatic RCC treated with this combined therapy.…”

“…Furthermore, in Japan, molecular‐targeted agents for RCC were not approved by the National Health Insurance until April 2008. Accordingly, we have performed combined immunotherapy with interferon‐α (IFN‐α) and low‐dose interleukin‐2 (IL‐2) as a primary treatment for patients with metastatic RCC, and we have preliminarily reported favorable outcomes of this combined therapy 6 …”

“…Accordingly, we have performed combined immunotherapy with interferon-a (IFN-a) and low-dose interleukin-2 (IL-2) as a primary treatment for patients with metastatic RCC, and we have preliminarily reported favorable outcomes of this combined therapy. 6 It would be necessary to establish a system for predicting the efficacy of immunotherapy in patients with advanced RCC, as the response rate to immunotherapy against RCC is not satisfactorily high and severe adverse effects occasionally accompany this treatment. 7 To date, several factors have been identified as predictors of susceptibility to immunotherapy for advanced RCC, such as performance status, histological subtype and metastatic site; [8][9][10] however, it remains largely unknown whether adding the assessment of molecular markers in RCC to the conventional clinical parameters can contribute to enhanced accuracy in predicting responses to immunotherapy.…”