Current status of cytokine therapy in management of patients with metastatic renal cell carcinoma

Abstract

Studies examining the efficacy of immunotherapy have used a variety of end points such as response rate (RR), complete response (CR) or partial response (PR); rate of progression; and progression-free and median survival. However, these studies used different definitions of these end points and none was blinded.5 Further, RR has been reported to be an unreliable surrogate of survival. 5A meta-analysis 7 of 1042 patients found that the overall proportion of responses (CR and PR) to interferon-α was 12%. CRs were quite rare. Favourable characteristics of responders included patients with prior nephrectomy and patients with lung metastases. In this particular patient population, the proportion of objective responses was as high as 44%. 7 The average time from the start of treatment to an objective response was about 3-4 months. Metastases of the central nervous system tended not to respond to interferon, and soft-tissue disease tended to respond more readily than bony metastases. Results of a review of more than 1500 patients 8 suggest that the disease RR is between 12% and 15% for patients receiving interferon-α. CRs occurred in 2%-5% patients, usually in those with pulmonary metastases. The recently published Cochrane collaboration review 5 estimated a gain of 3.8 months and a 1-year risk of mortality reduction by 44% for patients randomized to interferon-α2a, compared with patients randomized to control arms. Toxicity with interferon-α includes fever, malaise, flulike symptoms and night sweats, and is markedly less than that with interleukin-2 (IL-2). S28 REVIEW AbstractCytokine therapy with interferon-α and interleukin-2 has arguably been the standard treatment for patients with metastatic renal cell carcinoma for more than 20 years. In this paper, the current evidence for the use of cytokine therapy in this patient population is discussed, including the significant toxicity associated with these agents. A low overall response rate and a marginal survival advantage are observed with interferon-α and interleukin-2; however, these therapies have significant toxicity and impair quality of life. Unlike the current tyrosine-kinase inhibitors, complete tumour responses may be seen with interleukin-2, but again this therapy has significant morbidity and mortality. Newer anti-angiogenesis agents may be combined with current standard cytokine therapy for patients with metastatic renal cell carcinoma.

Quality of life in patients with advanced renal cell carcinoma given nivolumab versus everolimus in CheckMate 025: a randomised, open-label, phase 3 trial

“…15,16 Newer targeted therapies like temsirolimus, sunitinib, and sorafenib have shown improved HRQoL compared with interferon-α. However, no direct comparisons between these agents have been reported that show an improvement in HRQoL.…”

Antiangiogenic therapy for advanced renal cell carcinoma: Management of treatment-related toxicities

“…These agents are associated with low response rates (<15%) and significant toxicities, which often limit their use and affect patient quality of life (QoL) [7]. …”

Treatment patterns and health outcomes in metastatic renal cell carcinoma patients treated with targeted systemic therapies in the UK

“…Cytokine therapy with interleukin-2 (IL-2) or interferon-alpha (IFN-α) had been the standard approach to treating mRCC patients for over 20 years. However, poor response rates, marginal survival benefit and significant toxicity [3] prompted the development of alternative treatment options for the majority of patients. As the understanding of the molecular biology underlying RCC has increased, specific molecular targets have been identified for potential therapies.…”