Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon Alfa-2b in advanced renal cell carcinoma

Michael B. Atkins, Joseph A. Sparano, Richard I. Fisher, Geoffrey R. Weiss, Kim A. Margolin, Kenneth I. Fink, Larry Rubinstein, Arthur Louie, James W. Mier, Rasim A. Gucalp, Jeffrey A. Sosman, David H. Boldt, James H. Doroshow, Frederick R. Aronson, Mario Sznol

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

Purpose: To determine better the activity of high-dose interieukin-2 (IL-2) either alone or in combination with interferon alfa-2b (IFN; Schering-Plough, Kenilworth, NJ) in patients with metastatic renal cell carcinoma, the IL-2 Working Group initiated a randomized phase II trial. Patients and Methods: Patients were randomly assigned to receive treatment with either IL-2 (Chiron Corp, Emery ville, CA) 1.33 mg/m2 (∼ 600,000 IU/kg) alone or IL-2 0.8 mg/m2 and IFN 3 × 106 U/m2 administered by bolus intravenous injection every 8 hours, days 1 to 5 and 15 to 19 (maximum, 28 doses). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and normal organ function. After 28 patients were entered onto each arm, the IL-2/IFN arm was closed because of a failure to meet predetermined efficacy criteria. An additional 43 patients (total, 71 ) were assigned to receive IL-2 alone. Results: Toxicities were similar for both study arms. Hypotension requiring pressors was the most frequent dose-limiting toxicity. Only 11 of 99 patients experienced severe toxicity; there were no irreversible side effects or treatment-related deaths. Responses were seen in three of 28 patients (11%) on IL-2/IFN (three partial responses [PRs] lasting 14, 7, and 7 months) and 12 of 71 patients (17%) on IL-2 alone (four complete responses [CRs] and eight PRs). Six of the partial responders on IL-2 and two on IL-2/IFN experienced greater than 90% reduction in tumor mass. Ten of the 12 responders to IL-2 have ongoing responses of 12 + to 26 + months in duration. Conclusion: We conclude that both IL-2 and IL-2/IFN therapy have activity in metastatic renal cell carcinoma. In particular, therapy with high-dose IL-2 alone produces meaningful and durable responses with manageable and reversible toxicity. This study supports the contention that high-dose IL-2 represents the treatment of choice in selected patients with advanced renal cell carcinoma.

Original languageEnglish (US)
Pages (from-to)661-670
Number of pages10
JournalJournal of Clinical Oncology
Volume11
Issue number4
StatePublished - 1993
Externally publishedYes

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interferon alfa-2b
Renal Cell Carcinoma
Interleukin-2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon Alfa-2b in advanced renal cell carcinoma. / Atkins, Michael B.; Sparano, Joseph A.; Fisher, Richard I.; Weiss, Geoffrey R.; Margolin, Kim A.; Fink, Kenneth I.; Rubinstein, Larry; Louie, Arthur; Mier, James W.; Gucalp, Rasim A.; Sosman, Jeffrey A.; Boldt, David H.; Doroshow, James H.; Aronson, Frederick R.; Sznol, Mario.

In: Journal of Clinical Oncology, Vol. 11, No. 4, 1993, p. 661-670.

Research output: Contribution to journalArticle

Atkins, MB, Sparano, JA, Fisher, RI, Weiss, GR, Margolin, KA, Fink, KI, Rubinstein, L, Louie, A, Mier, JW, Gucalp, RA, Sosman, JA, Boldt, DH, Doroshow, JH, Aronson, FR & Sznol, M 1993, 'Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon Alfa-2b in advanced renal cell carcinoma', Journal of Clinical Oncology, vol. 11, no. 4, pp. 661-670.
Atkins, Michael B. ; Sparano, Joseph A. ; Fisher, Richard I. ; Weiss, Geoffrey R. ; Margolin, Kim A. ; Fink, Kenneth I. ; Rubinstein, Larry ; Louie, Arthur ; Mier, James W. ; Gucalp, Rasim A. ; Sosman, Jeffrey A. ; Boldt, David H. ; Doroshow, James H. ; Aronson, Frederick R. ; Sznol, Mario. / Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon Alfa-2b in advanced renal cell carcinoma. In: Journal of Clinical Oncology. 1993 ; Vol. 11, No. 4. pp. 661-670.
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abstract = "Purpose: To determine better the activity of high-dose interieukin-2 (IL-2) either alone or in combination with interferon alfa-2b (IFN; Schering-Plough, Kenilworth, NJ) in patients with metastatic renal cell carcinoma, the IL-2 Working Group initiated a randomized phase II trial. Patients and Methods: Patients were randomly assigned to receive treatment with either IL-2 (Chiron Corp, Emery ville, CA) 1.33 mg/m2 (∼ 600,000 IU/kg) alone or IL-2 0.8 mg/m2 and IFN 3 × 106 U/m2 administered by bolus intravenous injection every 8 hours, days 1 to 5 and 15 to 19 (maximum, 28 doses). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and normal organ function. After 28 patients were entered onto each arm, the IL-2/IFN arm was closed because of a failure to meet predetermined efficacy criteria. An additional 43 patients (total, 71 ) were assigned to receive IL-2 alone. Results: Toxicities were similar for both study arms. Hypotension requiring pressors was the most frequent dose-limiting toxicity. Only 11 of 99 patients experienced severe toxicity; there were no irreversible side effects or treatment-related deaths. Responses were seen in three of 28 patients (11{\%}) on IL-2/IFN (three partial responses [PRs] lasting 14, 7, and 7 months) and 12 of 71 patients (17{\%}) on IL-2 alone (four complete responses [CRs] and eight PRs). Six of the partial responders on IL-2 and two on IL-2/IFN experienced greater than 90{\%} reduction in tumor mass. Ten of the 12 responders to IL-2 have ongoing responses of 12 + to 26 + months in duration. Conclusion: We conclude that both IL-2 and IL-2/IFN therapy have activity in metastatic renal cell carcinoma. In particular, therapy with high-dose IL-2 alone produces meaningful and durable responses with manageable and reversible toxicity. This study supports the contention that high-dose IL-2 represents the treatment of choice in selected patients with advanced renal cell carcinoma.",
author = "Atkins, {Michael B.} and Sparano, {Joseph A.} and Fisher, {Richard I.} and Weiss, {Geoffrey R.} and Margolin, {Kim A.} and Fink, {Kenneth I.} and Larry Rubinstein and Arthur Louie and Mier, {James W.} and Gucalp, {Rasim A.} and Sosman, {Jeffrey A.} and Boldt, {David H.} and Doroshow, {James H.} and Aronson, {Frederick R.} and Mario Sznol",
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T1 - Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon Alfa-2b in advanced renal cell carcinoma

AU - Atkins, Michael B.

AU - Sparano, Joseph A.

AU - Fisher, Richard I.

AU - Weiss, Geoffrey R.

AU - Margolin, Kim A.

AU - Fink, Kenneth I.

AU - Rubinstein, Larry

AU - Louie, Arthur

AU - Mier, James W.

AU - Gucalp, Rasim A.

AU - Sosman, Jeffrey A.

AU - Boldt, David H.

AU - Doroshow, James H.

AU - Aronson, Frederick R.

AU - Sznol, Mario

PY - 1993

Y1 - 1993

N2 - Purpose: To determine better the activity of high-dose interieukin-2 (IL-2) either alone or in combination with interferon alfa-2b (IFN; Schering-Plough, Kenilworth, NJ) in patients with metastatic renal cell carcinoma, the IL-2 Working Group initiated a randomized phase II trial. Patients and Methods: Patients were randomly assigned to receive treatment with either IL-2 (Chiron Corp, Emery ville, CA) 1.33 mg/m2 (∼ 600,000 IU/kg) alone or IL-2 0.8 mg/m2 and IFN 3 × 106 U/m2 administered by bolus intravenous injection every 8 hours, days 1 to 5 and 15 to 19 (maximum, 28 doses). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and normal organ function. After 28 patients were entered onto each arm, the IL-2/IFN arm was closed because of a failure to meet predetermined efficacy criteria. An additional 43 patients (total, 71 ) were assigned to receive IL-2 alone. Results: Toxicities were similar for both study arms. Hypotension requiring pressors was the most frequent dose-limiting toxicity. Only 11 of 99 patients experienced severe toxicity; there were no irreversible side effects or treatment-related deaths. Responses were seen in three of 28 patients (11%) on IL-2/IFN (three partial responses [PRs] lasting 14, 7, and 7 months) and 12 of 71 patients (17%) on IL-2 alone (four complete responses [CRs] and eight PRs). Six of the partial responders on IL-2 and two on IL-2/IFN experienced greater than 90% reduction in tumor mass. Ten of the 12 responders to IL-2 have ongoing responses of 12 + to 26 + months in duration. Conclusion: We conclude that both IL-2 and IL-2/IFN therapy have activity in metastatic renal cell carcinoma. In particular, therapy with high-dose IL-2 alone produces meaningful and durable responses with manageable and reversible toxicity. This study supports the contention that high-dose IL-2 represents the treatment of choice in selected patients with advanced renal cell carcinoma.

AB - Purpose: To determine better the activity of high-dose interieukin-2 (IL-2) either alone or in combination with interferon alfa-2b (IFN; Schering-Plough, Kenilworth, NJ) in patients with metastatic renal cell carcinoma, the IL-2 Working Group initiated a randomized phase II trial. Patients and Methods: Patients were randomly assigned to receive treatment with either IL-2 (Chiron Corp, Emery ville, CA) 1.33 mg/m2 (∼ 600,000 IU/kg) alone or IL-2 0.8 mg/m2 and IFN 3 × 106 U/m2 administered by bolus intravenous injection every 8 hours, days 1 to 5 and 15 to 19 (maximum, 28 doses). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and normal organ function. After 28 patients were entered onto each arm, the IL-2/IFN arm was closed because of a failure to meet predetermined efficacy criteria. An additional 43 patients (total, 71 ) were assigned to receive IL-2 alone. Results: Toxicities were similar for both study arms. Hypotension requiring pressors was the most frequent dose-limiting toxicity. Only 11 of 99 patients experienced severe toxicity; there were no irreversible side effects or treatment-related deaths. Responses were seen in three of 28 patients (11%) on IL-2/IFN (three partial responses [PRs] lasting 14, 7, and 7 months) and 12 of 71 patients (17%) on IL-2 alone (four complete responses [CRs] and eight PRs). Six of the partial responders on IL-2 and two on IL-2/IFN experienced greater than 90% reduction in tumor mass. Ten of the 12 responders to IL-2 have ongoing responses of 12 + to 26 + months in duration. Conclusion: We conclude that both IL-2 and IL-2/IFN therapy have activity in metastatic renal cell carcinoma. In particular, therapy with high-dose IL-2 alone produces meaningful and durable responses with manageable and reversible toxicity. This study supports the contention that high-dose IL-2 represents the treatment of choice in selected patients with advanced renal cell carcinoma.

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