Treatment of advanced renal cell cancer with recombinant interferon alpha as a single agent and in combination with medroxyprogesterone acetate

Abstract

The response rates in metastatic renal cell cancer (RCC) after chemotherapy, hormonal treatment, or immunotherapy rarely exceed 15%. Recently, interferon alpha (IFN alpha) was used for treatment of this disease in several studies which also demonstrated response rates of 15%. In order to test whether IFN therapy combined with hormones would result in higher response rates we compared single agent IFN therapy with a combined therapy of rIFN alpha 2C plus medroxyprogesterone acetate (MPA) in a randomized multicenter trial. The rIFN alpha 2C (2MU) was given s.c. 5 times per week for 8-12 weeks and subsequently once weekly until week 48. In the combined treatment, 750 mg MPA was given p.o. daily until week 48 in addition to the IFN as described. The overall response rate in 93 evaluable patients was 5.4% corresponding to 2 complete and 3 partial responses. Median survival was 7 months in both treatment groups. These data confirm the ineffectivity of low IFN doses for treatment of RCC. The low response rate is not increased by addition of MPA to IFN. The analysis of other IFN studies suggests that not only IFN doses but also IFN sources may influence response rates in metastatic RCC.

Bevacizumab Plus Interferon Alfa Compared With Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: CALGB 90206

“…Previous attempts in metastatic RCC of combining other agents with immunotherapy have not demonstrated benefit over monotherapy. [4][5][6] It is noteworthy that the mechanism of these two agents may not be entirely independent, as IFN has demonstrated antiangiogenic effects 23 and antibody-mediated VEGF inhibition has antitumor effects through improvement in dendritic cell function.…”

“…[1][2][3] The addition of interleukin-2, hormonal therapy, or antiproliferative agents such as cis-retinoic acid to IFN has not demonstrated significant advantages over IFN monotherapy in randomized trials. [4][5][6] The pathogenesis of RCC has been further elucidated, resulting in identification of relevant therapeutic targets. Von Hippel-Lindau (VHL) syndrome is an autosomal dominant disorder caused by silencing of the VHL tumor suppressor gene and is associated with increased susceptibility to vascular tumors, including the prominent occurrence of clear-cell RCC.…”

Subcutaneous IL-2 and Low-Dose IFN-α2a in the Treatment of Unselected Patients with Advanced Renal Cell Cancer

“…Another reason for the lack of remissions in the present study compared with other studies using IL-2/IFN-a combination therapy for metastatic RCC [23][24][25] may be the low rIFN-a dose used. A dose-response relationship has already been described for single rIFN-a regimens [26,27]. IL-2 can induce peripheral blood mononuclear cells to produce a variety of cytokines.…”

A medical oncologist’s approach to immunotherapy for advanced renal tumors: Is nephrectomy indicated?

“…The overall response rates of patients treated with INFα-2a range from 10% to 20%, with a small subset of patients having a long-term survival [34,35]. In several phase 3 trials, INF-treated patients lived longer than those undergoing progesterone therapy or taking vinblastine [36][37][38]. Thus, INF alone is a standard of care therapy for metastatic renal cancer.…”