High dose interleukin-2 (Aldesleukin) - expert consensus on best management practices-2014

Journal for ImmunoTherapy of Cancer

Michael B Atkins⁷  James N Lowder³  Ahmad A Tarhini⁴  Sanjiv S Agarwala¹  Howard L Kaufman⁵  Douglas J Schwartzentruber²  Janice P Dutcher⁶ 

[1] Chief of Medical Oncology and Professor of Medicine, St. Luke¿s Cancer Center, Bethlehem 18015, PA, USA;Associate Director of Clinical Operations, Professor of Surgery, IU Simon Cancer Center, 550 N University Blvd, Indianapolis 46202, IN, USA;Senior Medical Director, Prometheus Laboratories Inc, 9410 Carroll Park Drive, San Diego 92121, CA, USA;Associate Professor of Medicine and Translational Science, University of Pittsburgh Cancer Institute, Suite 555, 5150 Centre Ave, Pittsburgh 15232, PA, USA;Chief Surgical Officer and Associate Director for Clinical Science, Professor of Surgery, Rutgers Cancer Center Institute of New Jersey, 195 Little Albany Street, Room 2007, New Brunswick 08901, NJ, USA;Associate Director, Cancer Research Foundation, Chappaqua, NY, USA;Deputy Director, Professor of Medicine, Georgetown-Lombardi Comprehensive Cancer Center, 3970 Reservoir Rd NW, NRB-E501, Washington 20057, DC, USA

关键词: Treatment guidelines;    Melanoma;    Renal cell carcinoma;    Cytokines;    Clinical management;    Interleukin-2;   

Others  :  1139872
DOI  :  10.1186/s40425-014-0026-0

 received in 2014-04-25, accepted in 2014-07-16,  发布年份 2014

【 摘 要 】

Interleukin-2 (IL-2) was historically one of the few treatments for adults with stage IV solid tumors that could produce complete responses (CRs) that were often durable for decades without further therapy. The majority of complete responders with metastatic renal cell carcinoma (mRCC) and metastatic melanoma (mM) could probably be classified as ¿cures¿. Recent publications have suggested improved efficacy, perhaps due to improved patient selection based on a better understanding of clinical features predicting outcomes. Guidelines for clinical management were established from experience at the National Cancer Institute (NCI) and an affiliation of institutions known as the Cytokine Working Group (CWG), who were among the first to utilize HD IL-2 treatment outside of the NCI. As new centers have opened, further management variations have emerged based upon center-specific experience, to optimize administration of IL-2 and provide high quality care for patients at each individual site. Twenty years of evolution in differing environments has led to a plethora of clinical experience and effective management approaches. The goal of this review is to summarize the spectrum of HD IL-2 treatment approaches, describing various effective strategies that incorporate newer adjunctive treatments for managing the side effects of IL-2 in patients with mRCC and mM. The goal for IL-2 therapy is typically to administer the maximum number of doses of IL-2 without putting the patient at unacceptable risk for severe, irreversible toxicity. This review is based upon a consensus meeting and includes guidelines on pre-treatment screening, criteria for administration and withholding doses, and defines consensus criteria for safe administration and toxicity management. The somewhat heterogeneous best practices of 2014 will be compared and contrasted with the guidelines provided in 2001 and the package inserts from 1992 and 1998.

【 授权许可】

   
2014 Dutcher et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P, Seipp CA, Rogers-Freezer L, Morton KE, White DE, Liewehr DJ, Merino MJ, Rosenberg SA: Randomized study of high-dose and low-dose Interleukin-2 in patients with metastatic renal cell cancer. J Clin Oncol 2003, 21:3127-3132.
• [2]McDermott DF, Regan MM, Clark JI, Flaherty LE, Weiss GR, Logan TF, Kirkwood JM, Gordon MS, Sosman JA, Ernstoff MS, Tretter CPG, Urba WJ, Smith JW, Margolin KA, Mier JW, Gollob JA, Dutcher JP, Atkins MB: Randomized phase III trial of high dose Interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol 2005, 23:133-141.
• [3]Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Wiess G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, Paradise C, Kunkel L, Rosenberg SA: High dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999, 17:2105-2116.
• [4]Atkins MB, Kunkel L, Sznol M, Rosenberg SA: High dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am 2000, 6(Suppl 1):S11-S14.
• [5]Margolin KA, Rayner AA, Hawkins MJ, Atkins MB, Dutcher JP, Fisher RI, Weiss GR, Doroshow JH, Jaffe HS, Roper M: Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: analysis of toxicity and management guidelines. J Clin Oncol 1989, 7:486-498.
• [6]Schwartzentruber DJ: Review: guidelines for the safe administration of high-dose interleukin-2. J Immunotherapy 2001, 24:287-293.
• [7]Kammula US, White DE, Rosenberg SA: Trends in the safety of high dose bolus interleukin-2 administration in patients with metastatic cancer. Cancer 1998, 83:797-805.
• [8]Dutcher J, Atkins MB, Wiess G, Margolin K, Clark J, Sosman J, Logan T, Aronson F, Meir J: Kidney Cancer: The Cytokine Working Group experience (1986¿2001). Part II: Management of IL2- toxicity and studies with other cytokines. Med Oncol 2001, 18:209-2109.
• [9]McDermott DF, Ghebremichael MS, Signoretti S, Margolin KA, Clark J, Sosman JA, Dutcher JP, French M, Regan MM, Atkins MB: The high-dose aldesleukin (HD-IL2) ¿Select¿ trial in patients with metastatic renal cell carcinoma. J Clin Oncol 2011, 29(Suppl 7):abst 321.
• [10]McDermott D, Ghebremichael M, Signoretti S, Margolin KA, Clark J, Sosman JA, Dutcher JP, French M, Regan MM, Atkins MB: The high dose aldesleukin (HD IL-2) ¿Select¿ trial in patients with metastatic renal cell carcinoma. J Immunother 2010, 33:903-904. abstract
• [11]Hawkins R, Galvis V, Shablak A, Spencer-Shaw A, Thistlethwaite F, Shanks J, Dalal N: Selecting patients for high-dose interleukin-2 on the basis of tumour histology. Ann Oncol 2012, 23(Suppl 9):ix267. ESMO abst # 808P
• [12]Acquavella N, Kluger H, Rhee J, Farber L, Tara H, Ariyan S, Narayan D, Kelly W, Sznol M: Toxicity and activity of a twice daily high-dose bolus interleukin-2 regimen in patients with metastatic melanoma and metastatic renal cell cancer. J Immunother 2008, 31:569-576.
• [13]Dandamudi UB, Ghebremichael M, Sosman JA, Clark JI, McDermott DF, Atkins MB, Dutcher JP, Urba WJ, Regan MM, Puzanov I, Crocenzi TS, Curti BD, Vaishampayan UN, Crosby NA, Margolin KA, Ernstoff MS: A phase II study of bevacizumab and high-dose interleukin-2 in patients with metastatic renal cell carcinoma: a cytokine working group study. J Immunother 2013, 36:490-495.
• [14]Dutcher JP: High dose interleukin-2 for the treatment of renal cell carcinoma: managing toxicities for better outcomes. Kidney Cancer J 2010, 8:22-26.
• [15]Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT, Seipp CA, Simpson C, Reichert CM: Observation on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2. N Engl J Med 1985, 313:1485-1488.
• [16]Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson C, White DE: 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 1987, 316:889-905.
• [17]Rosenberg SA, Yang JC, White DE, Steinberg SM: Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2. Ann Surg 1998, 228:307-319.
• [18]Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DH: Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin-2. JAMA 1994, 271:907-913.
• [19]Dutcher JP, Creekmore S, Weiss GR, Margolin K, Markowitz AB, Roper M, Parkinson D, Ciobanu N, Fisher RI, Boldt DH: A phase II study of high dose interleukin-2 (IL2) and lymphokine activated killer (LAK) cells in patients with metastatic malignant melanoma. J Clin Oncol 1989, 7:477-485.
• [20]Fisher RI, Coltman CA, Doroshow JH, Rayner AA, Hawkins MJ, Mier JW, Wiernik P, McMannis JD, Weiss GR, Margolin KA, Gemlo BT, Hoth DF, Parkinson DR, Paietta E: Metastatic renal cancer treated with Interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 1988, 4:518-523.
• [21]Lotze MT, Matory YL, Rayner AA, Ettinghausen SE, Vetto JT, Seipp CA, Rosenberg SA: Clinical effects and toxicity of interleukin-2 in patients with cancer. Cancer 1986, 58:2764-2772.
• [22]Rosenstein M, Ettinghausen SE, Rosenberg SA: Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin-2. J Immunol 1986, 137:1735-1742.
• [23]Mier JW, Aronson FR, Numerof RP, Vachino G, Atkins MB: Toxicity of immunotherapy with Interleukin-2 and lymphokine-activated killer cells. Pathol Immunopathol Res 1988, 7:459-476.
• [24]Ognibene FP, Rosenberg SA, Lotze M, Skibber J, Parker MM, Shelhamer JH, Parrillo JE: Interleukin-2 administration causes reversible hemodynamic changes and left ventricular dysfunction similar to those seen in septic shock. Chest 1988, 94:750-754.
• [25]Lee RE, Lotze MT, Skibber JM, Tucker E, Bonow RO, Ognibene FP, Carrasquillo JA, Shelhamer JH, Parrillo JE, Rosenberg SA: Cardiorespiratory effects of immunotherapy with interleukin-2. J Clin Oncol 1989, 7:7-20.
• [26]Gaynor E, Vitek L, Sticklin L, Creekmore SP, Ferraro ME, Thomas JX Jr, Fisher SG, Fisher RI: The hemodynamic effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 1988, 109:953-958.
• [27]Mier JW, Vachino G, van der Meer JW, Numerof RP, Adams S, Cannon JG, Bernheim HA, Atkins MB, Parkinson DR, Dinarello CA: Induction of circulating tumor necrosis factor as a mechanism for the febrile response to IL-2 in cancer patients. J Clin Immunol 1988, 8:426-436.
• [28]Baumgart DC, Lowder JN, Targan SR, Sandborn WJ, Frankel MB: Transient Cytokine-Induced Liver Injury Following Administration of the Humanized Anti-CD3 Antibody Visilizumab (HuM291) in Crohn¿s Disease. Am J Gastroenter 2009, 104:868-876.
• [29]Wan L, Bellomo R, Di Giantomasso D, Ronco C: The pathogenesis of septic acute renal failure. Curr Opin Crit Care 2003, 9:496-502.
• [30]Guleria AS, Yang JC, Topalian SL, Weber JS, Parkinson DR, MacFarlane MP, White RL, Steinberg SM, White DE, Einhorn JH: Renal dysfunction associated with the administration of high-dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal cell carcinoma. J Clin Oncol 1994, 12:2714-2722.
• [31]Shalmi CI, Dutcher JP, Feinfeld DA, Chun KJ, Saleemi KR, Freeman LM, Lynn RI, Wiernik PH: Acute renal dysfunction during interleukin-2 treatment: suggestion of an intrinsic renal lesion. J Clin Oncol 1990, 8:1839-1846.
• [32]Kozeny GA, Nicholas JD, Creekmore S, Sticklin L, Hano JE, Fisher RI: Effects of interleukin-2 immunotherapy on renal function. J Clin Oncol 1988, 6:1170-1176.
• [33]Klemper MS, Noring R, Mier JW, Atkins MB: An acquired chemotactic defect in neutrophils from patients receiving interleukin-2 immunotherapy. N Engl J Med 1990, 322:959-965.
• [34]Pockaj BA, Topalian S, Steinberg SM, White DE, Rosenberg SA: Infectious complications associated with interleukin-2 administration: a retrospective review of 935 treatment courses. J Clin Oncol 1993, 11:136-147.
• [35]Royal RE, Steinberg SM, Krouse RS, Heywood G, White DE, Hwu P, Marincola FM, Parkinson DR, Schwartzentruber DJ, Topalian SL, Yang JC, Rosenberg SA: Correlates of response to IL-2 therapy in patients treated for metastatic renal cancer and melanoma. Cancer J Sci Am 1996, 2:91-98.
• [36]Upton MP, Parker RA, Youmans A, McDermott DF, Atkins MB: Histologic predictors of renal cell carcinoma response to interleukin-2-based therapy. J Immunother 2005, 28:488-495.
• [37]Hawn MT, Graham LA, Richman JS, Itani KMF, Henderson WG, Maddox TM: Risk of major adverse cardiac events following noncardiac surgery in patients with coronary stents. JAMA 2013, 310:1462-1472.
• [38]Brilakis E, Banerjee S: Patient with coronary stents needs surgery: What to do? JAMA 2013, 310:1451-1452.
• [39]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: Retrospective analysis of the safety and efficacy of interleukin-2 after prior VEGF-targeted therapy in patients with advanced renal cell carcinoma. J Immunother 2009, 32:181-185.
• [40]Guirguis LM, Yang JC, White DE, Steinberg SE, Liewehr DJ, Rosenberg SA, Schwartzentruber DJ: Safety and efficacy of HD IL-2 therapy in patients with brain metastases. J Immunother 2002, 25:82-87.
• [41]Pockaj BA, Yang JC, Lotze MT, Lange JR, Spencer WF, Steinberg SM, Topalian SL, Schwartzentruber DJ, White DE, Rosenberg SA: A prospective randomized trial evaluating colloid versus crystalloid resuscitation in the treatment of the vascular leak syndrome associated with interleukin-2 therapy. J Immunother 1994, 15:22-28.
• [42]Lindsey KR, Rosenberg SA, Sherry RM: Impact of the number of treatment courses on the clinical response of patients who receive high-dose bolus interleukin-2. J Clin Oncol 2000, 18:1954-1959.
• [43]Logan TF, Dutcher JP, Flaherty LE, Sosman JA, Ernstoff MS, Clark JI, Atkins MB: A Cytokine Working Group (CWG) phase II study of intermediate dose bolus interleukin-2 (IL-2) for renal cell carcinoma patients ineligible to receive high dose IL-2 due to inadequate organ function. Proc Am Soc Clin Oncol 2002, 21:15a. abst #57
• [44]Finkelstein S, Carey T, Fricke I, Yu D, Goetz D, Gratz M, Dunn M, Urbas P, Daud A, DeConti R, Antonia S, Gabrilovich D, Fishman M: Changes in dendritic cell phenotype after a new high-dose weekly schedule of interleukin-2 therapy for kidney cancer and melanoma. J Immunother 2010, 33:817-827.
• [45]Annane D, Siami S, Jaber S, Martin C, Elatrous S, Deciere AD, Preiser JC, Outin H, Troche G, Charpentier C, Trouillet JL, Kimmoun A, Forceville X, Darmon M, Lesur O, Reignier J, Abroug F, Berger P, Clec¿h C, Cousson J, Thibault L, Chevret S: Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA 2013, 310:1809-1817.
• [46]Myburgh JA, Mythen MG: Resuscitation fluids. N Eng J Med 2013, 369:1243-1251.
• [47]Cormier JN, Hurst R, Vasselli J, Lee D, Kim CJ, McKee M, Venzon D, White D, Marincola FM, Rosenberg SA: A prospective randomized evaluation of the prophylactic use of low-dose dopamine in cancer patients receiving interleukin-2. J Immunother 1997, 20:292-300.
• [48]Sikora SS, Samsonov ME, Dookeran KA, Edgington H, Lotze MT: Peripheral nerve entrapment: an unusual adverse event with high-dose interleukin-2 therapy. Ann Oncol 1996, 7:535. Letter to the editor
• [49]Lee SH, Baig M, Rusciano V, Dutcher JP: Novel management of pruritus in patients treated with IL-2 for metastatic renal cell carcinoma and malignant melanoma. J Immunother 2010, 33:1010-1013.
• [50]Oleksowicz L, Strack M, Dutcher JP, Sussman I, Caliendo G, Joseph Sparano J, Wiernik PH: A distinct coagulopathy associated with interleukin-2 therapy. Br J Haematol 1994, 88:892-894.
• [51]Nakagawa K, Miller FN, Sims DE, Lentsch AB, Miyazaki M, Edwards MJ: Mechanisms of Interleukin-2-induced hepatic toxicity. Cancer Res 1996, 56:507-510.
• [52]Mier JW, Dinarello CA, Atkins MB, Punsal PI, Perlmutter DJ: Regulation of hepatic acute phase protein synthesis by products of interleukin 2 (IL-2)-stimulated human peripheral blood mononuclear cells. J Immunol 1971, 139:1268-1272.
• [53]Atkins MB, Mier JW, Parkinson DR, Gould JA, Berkman EM, Kaplan MM: Hypothyroidism after treatment with interleukin-2 and lymphokine activated killer cells. N Engl J Med 1988, 318:1557-1563.
• [54]Weijl NI, van der Harst D, Brand A, Kooy Y, Van Luxemburg S, Schroder J, Lentjes E, Van Rood JJ, Cleton FJ, Osanto S: Hypothyroidism during immunotherapy with interleukin-2 is associated with antithyroid antibodies and response to treatment. J Clin Oncol 1993, 11:376-383.
• [55]Krouse RS, Royal RE, Heywood G, Heywood G, Weintraub BD, White DE, Steinberg SM, Rosenberg SA, Schwartzentruber DJ: Thyroid dysfunction in 281 patients with metastatic melanoma or renal carcinoma treated with interleukin-2 alone. J Immunother Emphasis Tumor Immunol 1995, 18(4):272-278.
• [56]Choyke PL, Miller DL, Lotze MT, Whiteis JM, Ebbitt B, Rosenberg SA: Delayed reactions to contrast media after interleukin-2 immunotherapy. Radiology 1992, 183:111-114.
• [57]Lee DS, White DE, Hurst R, Rosenberg SA, Yang JC: Patterns of relapse and response to retreatment in patients with metastatic melanoma or renal cell carcinoma who responded to interleukin-2-based immunotherapy. Cancer J Sci Am 1998, 4:86-93.
• [58]Mavroukakis SA, Muehlbauer PM, White RL Jr, Schwartzentruber DJ: Clinical pathways for managing patients receiving interleukin 2. Clin J Oncol Nurs 2001, 5:207-216.
• [59]Coventry BJ, Ashdown ML: The 20th anniversary of interleukin-2 therapy: bimodal role explaining longstanding random induction of complete clinical responses. Cancer Manag Res 2012, 4:215-221.