Skip to main content
Erschienen in: Cancer Chemotherapy and Pharmacology 1/2017

23.12.2016 | Original Article

Clinical outcome of high-dose bolus intravenous interleukin-2 with a modified administration schedule for Asian patients with metastatic renal cell carcinoma

verfasst von: Ji Young Lee, Cheryn Song, Bum Sik Hong, Jun Hyuk Hong, Hanjong Ahn, Jae Lyun Lee

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The standard regimen of high-dose interleukin-2 (HDIL-2) for metastatic renal cell carcinoma (RCC) is two cycles separated by 9 days, which constitutes one course. Each course is separated by an 8–12 weeks. However, the 9-day interval between each HDIL-2 cycle is often not long enough to allow recovery from adverse effects. Therefore, we modified HDIL-2 schedules by increasing the interval between each cycle without changing the total cumulative doses of IL-2.

Methods

Clinical data from 37 patients who were treated with modified HDIL-2 schedule were reviewed. Patients received the first dose of IL-2 on day 1 and took subsequent doses every 8 h for a maximum of 14 doses each cycle. Treatment was repeated every 4 weeks, and a maximum of six cycles were planned.

Results

The overall response rate was 35% including two patients with complete response. With a median follow-up duration of 46.9 months, median progression-free survival was 16.0 months (95% CI 10.2–21.7 months) and median overall survival was 58.9 months (95% CI 49.6–68.3 months) with a 3-year overall survival rate of 77.8%. Toxicity profile was acceptable and comparable to standard HDIL-2 schedule. There were no treatment-related mortalities. The incidence of ≥grade 3 adverse events did not differ between patients who had prior exposure to vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI) and VEGFR TKI-naïve patients.

Conclusion

Modified HDIL-2 schedule seems to be a safe and effective option for selected Asian patients with metastatic RCC, even in patients with prior VEGFR TKI treatment.
Literatur
1.
Zurück zum Zitat Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC (1995) Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 13(3):688–696PubMed Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC (1995) Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 13(3):688–696PubMed
2.
Zurück zum Zitat Schwartzentruber DJ (2001) Guidelines for the safe administration of high-dose interleukin-2. J Immunother 24(4):287–293CrossRefPubMed Schwartzentruber DJ (2001) Guidelines for the safe administration of high-dose interleukin-2. J Immunother 24(4):287–293CrossRefPubMed
4.
Zurück zum Zitat Leibovich BC, Han KR, Bui MH, Pantuck AJ, Dorey FJ, Figlin RA, Belldegrun A (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(12):2566–2575. doi:10.1002/cncr.11851 CrossRefPubMed Leibovich BC, Han KR, Bui MH, Pantuck AJ, Dorey FJ, Figlin RA, Belldegrun A (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(12):2566–2575. doi:10.​1002/​cncr.​11851 CrossRefPubMed
6.
Zurück zum Zitat Royal RE, Steinberg SM, Krouse RS, Heywood G, White DE, Hwu P, Marincola FM, Parkinson DR, Schwartzentruber DJ, Topalian SL, Yang JC, Rosenberg SA (1996) Correlates of response to IL-2 therapy in patients treated for metastatic renal cancer and melanoma. Cancer J Sci Am 2(2):91–98PubMed Royal RE, Steinberg SM, Krouse RS, Heywood G, White DE, Hwu P, Marincola FM, Parkinson DR, Schwartzentruber DJ, Topalian SL, Yang JC, Rosenberg SA (1996) Correlates of response to IL-2 therapy in patients treated for metastatic renal cancer and melanoma. Cancer J Sci Am 2(2):91–98PubMed
8.
Zurück zum Zitat Clark J, Morse MA, Wong MKK, McDermott D, Kaufman H, Daniels GA, Pemitt JC, Hua H, Aung S (2016) Durability of responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2 (HD IL-2). J Clin Oncol 34(suppl 2S):abstr 511 Clark J, Morse MA, Wong MKK, McDermott D, Kaufman H, Daniels GA, Pemitt JC, Hua H, Aung S (2016) Durability of responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2 (HD IL-2). J Clin Oncol 34(suppl 2S):abstr 511
9.
Zurück zum Zitat McDermott DF, Cheng SC, Signoretti S, Margolin KA, Clark JI, Sosman JA, Dutcher JP, Logan TF, Curti BD, Ernstoff MS, Appleman L, Wong MK, Khushalani NI, Oleksowicz L, Vaishampayan UN, Mier JW, Panka DJ, Bhatt RS, Bailey AS, Leibovich BC, Kwon ED, Kabbinavar FF, Belldegrun AS, Figlin RA, Pantuck AJ, Regan MM, Atkins MB (2015) The high-dose aldesleukin “select” trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin Cancer Res 21(3):561–568. doi:10.1158/1078-0432.CCR-14-1520 CrossRefPubMed McDermott DF, Cheng SC, Signoretti S, Margolin KA, Clark JI, Sosman JA, Dutcher JP, Logan TF, Curti BD, Ernstoff MS, Appleman L, Wong MK, Khushalani NI, Oleksowicz L, Vaishampayan UN, Mier JW, Panka DJ, Bhatt RS, Bailey AS, Leibovich BC, Kwon ED, Kabbinavar FF, Belldegrun AS, Figlin RA, Pantuck AJ, Regan MM, Atkins MB (2015) The high-dose aldesleukin “select” trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin Cancer Res 21(3):561–568. doi:10.​1158/​1078-0432.​CCR-14-1520 CrossRefPubMed
10.
Zurück zum Zitat Park I, Cho YM, Lee JL, Ahn JH, Lee DH, Song C, Hong JH, Kim CS, Ahn H (2013) Prognostic factors of metastatic renal cell carcinoma with extensive sarcomatoid component. J Cancer Res Clin Oncol 139(5):817–827. doi:10.1007/s00432-013-1386-4 CrossRefPubMed Park I, Cho YM, Lee JL, Ahn JH, Lee DH, Song C, Hong JH, Kim CS, Ahn H (2013) Prognostic factors of metastatic renal cell carcinoma with extensive sarcomatoid component. J Cancer Res Clin Oncol 139(5):817–827. doi:10.​1007/​s00432-013-1386-4 CrossRefPubMed
11.
Zurück zum Zitat Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10):883–892. doi:10.1056/NEJMoa1113205 CrossRefPubMedPubMedCentral Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10):883–892. doi:10.​1056/​NEJMoa1113205 CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Shuch B, Said J, LaRochelle JC, Zhou Y, Li G, Klatte T, Pouliot F, Kabbinavar FF, Belldegrun AS, Pantuck AJ (2010) Histologic evaluation of metastases in renal cell carcinoma with sarcomatoid transformation and its implications for systemic therapy. Cancer 116(3):616–624. doi:10.1002/cncr.24768 CrossRefPubMedPubMedCentral Shuch B, Said J, LaRochelle JC, Zhou Y, Li G, Klatte T, Pouliot F, Kabbinavar FF, Belldegrun AS, Pantuck AJ (2010) Histologic evaluation of metastases in renal cell carcinoma with sarcomatoid transformation and its implications for systemic therapy. Cancer 116(3):616–624. doi:10.​1002/​cncr.​24768 CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat McDermott DF, Sosman JA, Sznol M, Massard C, Gordon MS, Hamid O, Powderly JD, Infante JR, Fasso M, Wang YV, Zou W, Hegde PS, Fine GD, Powles T (2016) Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study. J Clin Oncol 34(8):833–842. doi:10.1200/JCO.2015.63.7421 CrossRefPubMed McDermott DF, Sosman JA, Sznol M, Massard C, Gordon MS, Hamid O, Powderly JD, Infante JR, Fasso M, Wang YV, Zou W, Hegde PS, Fine GD, Powles T (2016) Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study. J Clin Oncol 34(8):833–842. doi:10.​1200/​JCO.​2015.​63.​7421 CrossRefPubMed
14.
Zurück zum Zitat Stinauer MA, Kavanagh BD, Schefter TE, Gonzalez R, Flaig T, Lewis K, Robinson W, Chidel M, Glode M, Raben D (2011) Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control. Radiat Oncol 6:34. doi:10.1186/1748-717X-6-34 CrossRefPubMedPubMedCentral Stinauer MA, Kavanagh BD, Schefter TE, Gonzalez R, Flaig T, Lewis K, Robinson W, Chidel M, Glode M, Raben D (2011) Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control. Radiat Oncol 6:34. doi:10.​1186/​1748-717X-6-34 CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Teh B, Bloch C, Galli-Guevara M, Doh L, Richardson S, Chiang S, Yeh P, Gonzalez M, Lunn W, Marco R, Jac J, Paulino A, Lu H, Butler E, Amato R (2007) The treatment of primary and metastatic renal cell carcinoma (RCC) with image-guided stereotactic body radiation therapy (SBRT). Biomed Imaging Interv J 3(1):e6. doi:10.2349/biij.3.1.e6 PubMedPubMedCentral Teh B, Bloch C, Galli-Guevara M, Doh L, Richardson S, Chiang S, Yeh P, Gonzalez M, Lunn W, Marco R, Jac J, Paulino A, Lu H, Butler E, Amato R (2007) The treatment of primary and metastatic renal cell carcinoma (RCC) with image-guided stereotactic body radiation therapy (SBRT). Biomed Imaging Interv J 3(1):e6. doi:10.​2349/​biij.​3.​1.​e6 PubMedPubMedCentral
16.
Zurück zum Zitat Dybal EJ, Haas GP, Maughan RL, Sud S, Pontes JE, Hillman GG (1992) Synergy of radiation therapy and immunotherapy in murine renal cell carcinoma. J Urol 148(4):1331–1337PubMed Dybal EJ, Haas GP, Maughan RL, Sud S, Pontes JE, Hillman GG (1992) Synergy of radiation therapy and immunotherapy in murine renal cell carcinoma. J Urol 148(4):1331–1337PubMed
17.
Zurück zum Zitat Samlowski WE, Majer M, Boucher KM, Shrieve AF, Dechet C, Jensen RL, Shrieve DC (2008) Multidisciplinary treatment of brain metastases derived from clear cell renal cancer incorporating stereotactic radiosurgery. Cancer 113(9):2539–2548. doi:10.1002/cncr.23857 CrossRefPubMed Samlowski WE, Majer M, Boucher KM, Shrieve AF, Dechet C, Jensen RL, Shrieve DC (2008) Multidisciplinary treatment of brain metastases derived from clear cell renal cancer incorporating stereotactic radiosurgery. Cancer 113(9):2539–2548. doi:10.​1002/​cncr.​23857 CrossRefPubMed
18.
Zurück zum Zitat Seung SK, Curti BD, Crittenden M, Walker E, Coffey T, Siebert JC, Miller W, Payne R, Glenn L, Bageac A, Urba WJ (2012) Phase 1 study of stereotactic body radiotherapy and interleukin-2-tumor and immunological responses. Sci Transl Med 4(137):137ra174. doi:10.1126/scitranslmed.3003649 CrossRef Seung SK, Curti BD, Crittenden M, Walker E, Coffey T, Siebert JC, Miller W, Payne R, Glenn L, Bageac A, Urba WJ (2012) Phase 1 study of stereotactic body radiotherapy and interleukin-2-tumor and immunological responses. Sci Transl Med 4(137):137ra174. doi:10.​1126/​scitranslmed.​3003649 CrossRef
19.
Zurück zum Zitat Klapper JA, Downey SG, Smith FO, Yang JC, Hughes MS, Kammula US, Sherry RM, Royal RE, Steinberg SM, Rosenberg S (2008) High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma: a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer 113(2):293–301. doi:10.1002/cncr.23552 CrossRefPubMedPubMedCentral Klapper JA, Downey SG, Smith FO, Yang JC, Hughes MS, Kammula US, Sherry RM, Royal RE, Steinberg SM, Rosenberg S (2008) High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma: a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer 113(2):293–301. doi:10.​1002/​cncr.​23552 CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Negrier S, Gomez F, Douillard JY, Ravaud A, Chevreau C, Buclon M, Perol D, Lasset C, Escudier B, Groupe Francais dI (2005) Prognostic factors of response or failure of treatment in patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d’Immunotherapie. World J Urol 23(3):161–165. doi:10.1007/s00345-004-0467-z CrossRefPubMed Negrier S, Gomez F, Douillard JY, Ravaud A, Chevreau C, Buclon M, Perol D, Lasset C, Escudier B, Groupe Francais dI (2005) Prognostic factors of response or failure of treatment in patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d’Immunotherapie. World J Urol 23(3):161–165. doi:10.​1007/​s00345-004-0467-z CrossRefPubMed
21.
Zurück zum Zitat Lentsch AB, Miller FN, Edwards MJ (1999) Mechanisms of leukocyte-mediated tissue injury induced by interleukin-2. Cancer Immunol Immunother 47(5):243–248CrossRefPubMed Lentsch AB, Miller FN, Edwards MJ (1999) Mechanisms of leukocyte-mediated tissue injury induced by interleukin-2. Cancer Immunol Immunother 47(5):243–248CrossRefPubMed
23.
Zurück zum Zitat Lam ET, Wong MK, Agarwal N, Redman BG, Logan T, Gao D, Flaig TW, Lewis K, Poust J, Monk P, Jarkowski A, Sendilnathan A, Bolden M, Kuzel TM, Olencki T (2014) Retrospective analysis of the safety and efficacy of high-dose interleukin-2 after prior tyrosine kinase inhibitor therapy in patients with advanced renal cell carcinoma. J Immunother 37(7):360–365. doi:10.1097/CJI.0000000000000044 CrossRefPubMedPubMedCentral Lam ET, Wong MK, Agarwal N, Redman BG, Logan T, Gao D, Flaig TW, Lewis K, Poust J, Monk P, Jarkowski A, Sendilnathan A, Bolden M, Kuzel TM, Olencki T (2014) Retrospective analysis of the safety and efficacy of high-dose interleukin-2 after prior tyrosine kinase inhibitor therapy in patients with advanced renal cell carcinoma. J Immunother 37(7):360–365. doi:10.​1097/​CJI.​0000000000000044​ CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Cho DC, Puzanov I, Regan MM, Schwarzberg T, Seery V, Lee MY, Liu V, Bhatt R, Koon H, Mier JW, Sosman JA, Atkins MB, McDermott DF (2009) Retrospective analysis of the safety and efficacy of interleukin-2 after prior VEGF-targeted therapy in patients with advanced renal cell carcinoma. J Immunother 32(2):181–185. doi:10.1097/CJI.0b013e3181952b1d CrossRefPubMed Cho DC, Puzanov I, Regan MM, Schwarzberg T, Seery V, Lee MY, Liu V, Bhatt R, Koon H, Mier JW, Sosman JA, Atkins MB, McDermott DF (2009) Retrospective analysis of the safety and efficacy of interleukin-2 after prior VEGF-targeted therapy in patients with advanced renal cell carcinoma. J Immunother 32(2):181–185. doi:10.​1097/​CJI.​0b013e3181952b1d​ CrossRefPubMed
Metadaten
Titel
Clinical outcome of high-dose bolus intravenous interleukin-2 with a modified administration schedule for Asian patients with metastatic renal cell carcinoma
verfasst von
Ji Young Lee
Cheryn Song
Bum Sik Hong
Jun Hyuk Hong
Hanjong Ahn
Jae Lyun Lee
Publikationsdatum
23.12.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 1/2017
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-016-3222-4

Weitere Artikel der Ausgabe 1/2017

Cancer Chemotherapy and Pharmacology 1/2017 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.