Abstract
Thirteen patients with metastatic renal cancer were treated in a phase II trial with interleukin-2, 21.6 million IU/m2 intravenously daily for five days on two consecutive weeks, starting 3 days after the administration of low dose cyclophosphamide 350 mg/m2 intravenously. Treatment cycles were repeated every 21 days. No responses were seen (95% Confidence Interval: 0–22%). The most common toxicities were fever, fatigue, hypotension, nausea/emesis, and myalgia/arthralgia. There were 11 episodes of Grade III toxicity including Grade III hypotension in 7 patients. Because of the significant toxicity and the lack of observed response, the study was discontinued. Cyclophosphamide and interleukin-2 at the dose and schedule used in this study has considerable toxicity and is unlikely to improve on response rates previously seen with other IL-2-based regimens in metastatic renal cancer.
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References
Boring CC, Squires TS, Tong T: Cancer statistics, 1993. CA: a cancer journal for clinicians 43:7–26, 1993
Yagoda A: New cytotoxic single-agent for renal cell carcinoma. In: Johnson DE, Logothetis CJ, von Eschenbach AC, eds. Systemic therapy for genitourinary cancers. Chicago: Year Book, 112–119, 1989
Taylor SA, Goodman P, Crawford ED, Stuckey WJ, Stephens RL, Gaynor ER: Phase II evaluation of didemnin B in advanced adenocarcinomas of the kidney. A Southwest Oncology Group study. Invest N Drugs 10:55–56, 1992
Witte RS, Elson P, Bryan GT, Trump DL: Trimetrexate in advanced renal cell carcinoma. An ECOG phase II study. Invest N Drugs 10:51–54, 1992
Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT, Seipp CA, Simpson CG, Reichert CM: Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313:1485–1492, 1985
Fisher RI, Coltman CA Jr, 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 Int Med 108:518–523 1988
Bukowski RM, Goodman P, Crawford ED, Sergi JS, Redman BG, Whitehead RP: Phase II trial of high-dose interleukin-2 in metastatic renal cell carcinoma: a Southwest Oncology Group study. J Nat Cancer Inst 82:143–146, 1990
Margolin KA, Rayner AA, Hawkins MJ, Atkins MB, Dutcher JP, Fisher RI, Weiss GR, Doroshow JH, Jaffe HS, Roper M, Parkinson DR, Wiernik PH, Creekmore SP, Boldt DH: Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: analysis of toxicity and management guidelines. J Clin Oncol 7:496–498, 1989
Siegel JP, Puri RK: Interleukin-2 toxicity. J Clin Oncol 9:694–704, 1991
Mitchell MS, Kempf RA, Harel W, Shau H, Boswell WD, Lind S, Dean G, Moore J, Bradley EC: Low-dose cyclophosphamide and low-dose interleukin-2 for malignant melanoma. Bull NY Acad Med 65:128–144, 1989
Bernard JT, Ameriso S, Kempf RA, Rosen P, Mitchell MS, Fisher M: Transient focal neurologic deficits complicating interleukin-2 therapy. Neurology 40:154–155, 1990
Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, White DE: A progress report on the treatment of 157 patients with advancer cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316:889–897, 1987
West WH, Tauer KW, Yannelli JR, Marshall GD, Orr DW, Thurman GB, Oldham RK: Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. N Engl J Med 316:898–905, 1987
Eindemann A, Hoffken H, Schmidt RE, Diehl V, Kloke O, Gamm H, Hayungs J, Oster W, Bohm M, Kolitz JE, Franks CR, Herrmann F, Mertelsmann RH: a phase II study of low-dose cyclophosphamide and recombinant human interleukin-2 in metastatic renal cell carcinoma and malignant melanoma. Cancer Immunol Immunother 28:275–281, 1989
Verdi CJ, Taylor CW, Croghan MK, Dalke P, Meyskens FL, Hersh EM: Phase I study of low-dose cyclophosphamide and recombinant interleukin-2 for the treatment of advanced cancer. J Immunother 11:286–291, 1992
Thompson JA, Shulman KL, Benyunes MC, Lindgren CG, Collins C, Lange PH, Bush WH Jr, Benz LA, Fefer A: Prolonged continuous intravenous infusion interleukin-2 and lymphokine-activated killer-cell therapy for metastatic renal cell carcinoma. J Clin Oncol 10: 960–968, 1992
Albertini MR, Sosman JA, Hank JA, Moore KH, Borchert A, Schell K, Kohler PC, Bechhofer R, Storer B, Sondel PM: The influence of autologous lymphokine-activated killer cell infusions on the toxicity and antitumor effect of repetitive cycles of interleukin-2. Cancer 66: 2457–2464, 1990
Budd GT, Murthy S, Finke J, Sergi J, Gibson V, Medendorp S, Barna B, Boyett J, Bukowski RM: Phase I trial of high-dose bolus interleukin-2 and interferon alfa-2a in patients with metastatic malignancy. J Clin Oncol 10: 804–809, 1992
Sznol M, Clark JW, Smith JW II, Steis RG, Urba WJ, Rubenstein LV, VanderMolen LA, Janik J, Sharfman WH, Fenton RG, Creekmore SP, Kremers P, Conlon K, Hursey J, Beveridge J, Longo DL: Pilot study of interleukin-2 and lymphokine-activated killer cells combined with immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a in patients with metastatic melanoma and renal cell carcinoma. J Nat Cancer Inst 84:929–937, 1992
Atzpodien J, Koerfer A, Evers P, Franks CR, Knueveropf J, Lopez-Haenninen E, Fischer M, Mohr H, Dalimann I, Hadam M: Low-dose subcutaneous recombinant interleukin-2 in advanced human malignancy: a phase II outpatient study. Mol Biother 2:18–26, 1990
Atzpodien J, Poliwoda H, Kirchner H: Alpha-interferon and interleukin-2 in renal cell carcinoma: studies in nonhospitalized patients. Semin Oncol 18(suppl 5): 108–112, 1991
Sleijfer DTh, Janssen RAJ, Buter J, de Vries EGE, Willemse PHB, Mulder NH: Phase II study of subcutaneous interleukin-2 in unselected patients with advanced renal cell cancer on an outpatient basis. J Clin Oncol 10:1119–1123, 1992
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Quan, W.D.Y., Dean, G.E., Lieskovsky, G. et al. Phase II study of low dose cyclophosphamide and intravenous interleukin-2 in metastatic renal cancer. Invest New Drugs 12, 35–39 (1994). https://doi.org/10.1007/BF00873233
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DOI: https://doi.org/10.1007/BF00873233