Abstract
This prospective, non-randomized study assessed toxicity and potential efficacy of low-dose granulocytemacrophage colony-stimulating factor (GM-CSF), interferon alpha (IFN) and interleukin 2 (IL-2) postoperatively in patients with high-risk renal cell carcinoma (RCC). Eligibility requirements were resected locally advanced (T3b-4 or N1–2) or metastatic (M1) RCC, no prior systemic therapy, and excellent organ function. Patients received treatment during 6 months: GM-CSF, 1 mcg/kg, 3 tiw, s.c., first week of each month; IFN, 10 MIU, 3 tiw, s.c., second week, and IL- 2, 1 MIU, 3 tiw, i.v., third week. Fourth week of each month was free from treatment. The primary end-point was diseasefree survival (DFS). Secondary end-points were progression rate, overall survival (OS), safety, and toxicity. Using the method of Dixon and Simon, the accrual goal was 35 patients. 35 patients were enrolled onto the study (28m/7f; median age = 46, range 21-71; ECOG 0-1; 14 (40%) pts with stage III and 21 (60%) pts with stage IV). Toxicity was minimal characterized by mainly flu-like syndrome and erythema in injection site. Median DFS was 14.1 months (95% CI, 3–20.2 months). At a median follow-up time of 5.1 years, progression rate was 65.7%, and OS was 40%. The median OS was 53.0 months (95% CI, 40.6–65.4 months). 5-years DFS and OS were similar between locally advanced and N2/M1 groups. Although the toxicities seen in this trial were low grade and regimen was well tolerated, low-dose GM-CSF, IFN and IL-2 did not improve DFS in comparison with historical control in patients with resected high-risk RCC.
Highlights
The estimated average 5-year survival rates in renal cell carcinoma (RCC) is 96% for patients presenting with stage I disease, 82% for stage II, 64% for stage III, and 23% for stage IV (DeVita and Rosenberg, 2008)
Randomized trials comparing adjuvant interferon alpha (IFN) or highdose interleukin 2 (IL-2) with observation alone in patients who had locally advanced, completely resected RCC showed that no delay in time to relapse or improvement in survival was associated with adjuvant therapy (Clark et al, 2003; Messing et al, 2003; Trump et al, 1996)
These immune responses are mediated by CD8+ T lymphocytes and the responses may be further amplified by cytokines secreted by CD4+ helper cells, such as IL-2 and IFN
Summary
The estimated average 5-year survival rates in renal cell carcinoma (RCC) is 96% for patients presenting with stage I disease, 82% for stage II, 64% for stage III, and 23% for stage IV (DeVita and Rosenberg, 2008). 20% to 30% of patients with localized tumors experience relapse. Adjuvant treatment after nephrectomy currently has no established role in patients who have undergone a complete resection of their tumor. Randomized trials comparing adjuvant interferon alpha (IFN) or highdose interleukin 2 (IL-2) with observation alone in patients who had locally advanced, completely resected RCC showed that no delay in time to relapse or improvement in survival was associated with adjuvant therapy (Clark et al, 2003; Messing et al, 2003; Trump et al, 1996). We hypothesized that granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN and IL-2 can stimulate large number of T-lymphocytes, antigen-presenting cells and can induct anti-tumor immunity in RCC patients. We performed a prospective, non-randomized trial evaluating toxicity and efficacy of 6-months course of low-dose GM-CSF, IFN and IL-2 postoperatively in patients with high-risk RCC
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