Abstract
Background
The objective of the current study was to determine the efficacy and safety of very low-dose interleukin-2 (IL-2), interferon (IFN)-α, and tegafur-uracil for patients with unresectable renal cell carcinoma (RCC), metastatic RCC, or both. Clinical prognostic factors were also investigated.
Methods
Fifty consecutive patients underwent a 3-week treatment cycle of IL-2 (0.7 × 106 Japanese reference units [JRU])/person on days 1–3 weekly), IFN-α (3 × 106 international units/person, on days 1–5 weekly), and tegafururacil (300 mg/person daily).
Results
The median follow-up after treatment initiation was 11.3 months. A median of three (range, 1–20) treatment cycles was administered. Of 47 eligible patients, 4 had a treatment response (3 complete responses and 1 partial response; objective response rate, 8.5%). The median progression-free and overall survivals were 8.3 months (95% confidence interval [CI], 5.5–10.9 months) and 38.8 months (95% CI, 27.8–49.7 months), respectively. Only 8 patients had grade III/IV toxicities. Two parameters, i.e., the absence of a previous nephrectomy and a low hemoglobin level, were identified as independent factors predictive of poor survival. Patients with low or intermediate risk (presence of none or one of the two prognostic factors) had a durable median survival exceeding 30 months. High-risk patients with both risk factors had rapid disease progression despite treatment.
Conclusion
While the effectiveness of this immunochemotherapy resulted in a limited antitumor response, low-and intermediate-risk patients with metastatic RCC seemed likely to have a survival benefit. Patient selection is essential to enhance treatment efficiency and avoid useless treatment for high-risk patients.
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References
Atkins MB, Regan M, McDermott D (2004) Update on the role of interleukin 2 and other cytokines in the treatment of patients with stage IV renal carcinoma. Clin Cancer Res 10:6342–6634
Atkins MB, Sparano J, Fisher RI, et al. (1993) Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma. J Clin Oncol 11:661–670
Atzpodien J, Lopez Hanninen E, et al. (1995) Multiinstitutional home-therapy trial of recombinant human interleukin-2 and interferon alfa-2 in progressive metastatic renal cell carcinoma. J Clin Oncol 13:497–501
Negrier S, Escudier B, Lasset C, et al. (1998) Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Francais d’Immunotherapie. N Engl J Med 338:1272–1278
Ravaud A, Delva R, Gomez F, et al. Groupe Francais d’Immunotherapie (2002) Subcutaneous interleukin-2 and interferon alpha in the treatment of patients with metastatic renal cell carcinoma. Less efficacy compared with intravenous interleukin-2 and interferon alpha. Results of a multicenter phase II trial from the Groupe Francais d’Immunotherapie. Cancer 95:2324–2330
Rosenberg SA, Lotze MT, Muul LM, et al. (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316:889–897
Dillman RO, Wiemann MC, Bury MJ, et al. (1997) Hybrid high-dose bolus/continuous infusion interleukin-2 in patients with metastatic renal cell carcinoma: a phase II trial of the National Biotherapy Study Group. Cancer Biother Radiopharm 12:5–11
Ravaud A, Negrier S, Cany L, et al. (1994) Subcutaneous low-dose recombinant interleukin 2 and alpha-interferon in patients with metastatic renal cell carcinoma. Br J Cancer 69:1111–1114
Atzpodien J, Lopez Hanninen E, Kirchner H, et al. (1995) Multi-institutional home-therapy trial of recombinant human interleukin-2 and interferon alfa-2 in progressive metastatic renal cell carcinoma. J Clin Oncol 13:497–501
Buzio C, De Palma G, Passalacqua R, et al. (1997) Effectiveness of very low doses of immunotherapy in advanced renal cell cancer. Br J Cancer 76:541–544
Buzio C, Andrulli S, Santi R, et al. (2001) Long-term immunotherapy with low-dose interleukin-2 and interferon-alpha in the treatment of patients with advanced renal cell carcinoma. Cancer 92:2286–2296
Lopez Hanninen E, Kirchner H, Atzpodien J (1996) Interleukin-2 based home therapy of metastatic renal cell carcinoma: risks and benefits in 215 consecutive single institution patients. J Urol 155:19–25
Atzpodien J, Kirchner H, Illiger HJ, et al. (2001) IL-2 in combination with IFN-alpha and 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial. Br J Cancer 85:1130–1136
Aso Y, Tazaki H, Umeda T, Marumo K (1989) A phase II trial of S-6820 (recombinant interleukin-2) on renal cell carcinoma (in Japanese). Biotherapy 3:999–1007
Makower D, Wadler S, Haynes H, Schwartz EI (1997) Interferon induces thymidine phosphorylase/platelet-derived endothelial cell growth factor expression in vivo. Clin Cancer Res 3:923–929
Morita T, Tokue A (1999) Biomodulation of 5-fluorouracil by interferon-alpha in human renal carcinoma cells: relationship to the expression of thymidine phosphorylase. Cancer Chemother Pharmacol 44:91–96
WHO handbook for reporting results of cancer treatment (1979) WHO offset publication No. 48. World Health Organization, Geneva
Atzpodien J, Hoffmann R, Franzke M, et al. (2002) Thirteen-year, long-term efficacy of interferon 2 alpha and interleukin 2-based home therapy in patients with advanced renal cell carcinoma. Cancer 95:1045–1050
Atzpodien J, Kirchner H, Jonas U, et al. (2004) Interleukin-2 and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a prospectively randomized trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). J Clin Oncol 22:1188–1194
Hutson TE, Quinn DI (2005) Cytokine therapy: a standard of care for metastatic renal cell carcinoma? Clin Genitourin Cancer 4:181–186
Négrier S, Caty A, Lesimple T, et al. (2000) Treatment of patients with metastatic renal carcinoma with a combination of subcutaneous interleukin-2 and interferon alfa with or without fluorouracil. Groupe Français d’Immunothérapie, Fédération Nationale des Centres de Lutte Contre le Cancer. J Clin Oncol 18:4009–4015
Suzuki K, Nukui A, Kobayashi M, et al. (1999) A case of pulmonary metastasis from renal cell carcinoma with complete response to interferon-α and tegafur/uracil but possibly UFT-induced liver dysfunction and leukoencephalopathy-like symptoms (in Japanese). Acta Urol Jpn 45:621–624
Akaza H, Tsukamoto T, Onishi T, et al. (2006) A low-dose combination therapy of interleukin-2 and interferon-alpha is effective for lung metastasis of renal cell carcinoma: a multicenter open study. Int J Clin Oncol 11:434–440
McDermott DF, Atkins MB (2004) Application of IL-2 and other cytokines in renal cancer. Expert Opin Biol Ther 4:455–468
Baaten G, Voogd AC, Wagstaff J (2004) A systematic review of the relation between interleukin-2 schedule and outcome in patients with metastatic renal cell cancer. Eur J Cancer 40: 1127–1144
Motzer RJ, Mazumdar M, Bacik J, et al. (1999) Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma J Clin Oncol 17:2530–2540
Negrier S, Gomez F, Douillard JY, et al. Groupe Francais d’Immunotherapie (2005) Prognostic factors of response of failure of treatment in patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d’Immunotherapie. World J Urol 23:161–165
Palmer PA, Vinke J, Philip T, et al. (1992) Prognostic factors for survival in patients with advanced renal cell carcinoma treated with recombinant interleukin-2. Ann Oncol 3:475–480
Fossa SD, Kramar A, Droz JP (1994) Prognostic factors and survival in patients with metastatic renal cell carcinoma treated with chemotherapy or interferon-alpha. Eur J Cancer 30A:1310–1314
Negrier S, Escudier B, Gomez F, et al. (2002) Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d’Immunotherapie. Ann Oncol 13:1460–1468
Leibovich BC, Han KR, Bui MH, et al. (2003) Scoring algorithm to predict survival after nephrectomy and immunotherapy in patients with metastatic renal cell carcinoma: a stratification tool for prospective clinical trials. Cancer 98:2566–2575
Atzpodien J, Royston P, Wandert T, et al. DGCIN — German Cooperative Renal Carcinoma Chemo-Immunotherapy Trials Group (2003) Metastatic renal carcinoma comprehensive prognostic system. Br J Cancer 88:348–353
Motzer RJ, Bacik J, Schwartz LH, et al. (2004) Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 22:454–463
Patel NP, Lavengood RW (1978) Renal cell carcinoma: natural history and results of treatment. J Urol 119:722–726
Yang JC, Haworth L, Sherry RM, et al. (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427–434
Motzer RJ, Hutson TE, Tomczak P, et al. (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124
Escudier B, Eisen T, Stadler WM, et al. (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134
Ryan CW, Goldman BH, Lara PN Jr, et al. (2007) Sorafenib with interferon alfa-2b as first-line treatment of advanced renal carcinoma: a phase II study of the Southwest Oncology Group. J Clin Oncol 25:3296–3301
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Kobayashi, M., Ikeda, H., Nukui, A. et al. Clinical outcome and prognostic survival factors in patients with advanced renal cell carcinoma treated with very low-dose interleukin-2, interferon-α, and tegafur-uracil: a single-institution experience. Int J Clin Oncol 13, 257–262 (2008). https://doi.org/10.1007/s10147-007-0752-0
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DOI: https://doi.org/10.1007/s10147-007-0752-0