Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma

Joseph A. Sparano, Richard I. Fisher, Margaret Sunderland, Kim Margolin, Mary Lou Ernest, Mario Sznol, Michael B. Atkins, Janice P. Dutcher, Kenneth C. Micetich, Geoffrey R. Weiss, James H. Doroshow, Frederick R. Aronson, Lawrence V. Rubinstein, James W. Mier

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Abstract

Purpose: To compare the response rate, survival, and toxicity of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus interferon alfa-2a (IFN-α) with high-dose IL-2 alone in patients with advanced melanoma in a randomized phase III trial design. Patients and Methods: Eighty-five patients with advanced melanoma were randomly assigned to receive IL-2 6 × 106 U/m2 per dose every 8 hours as tolerated for a maximum of 14 doses on days 1 through 5 and 15 through 19, or IL-2 4.5 × 106 U/m2 per dose, plus IFN-α 3 × 106 U/m2 using an identical schedule. A planned interim analysis was performed after 85 patients were entered, which forms the basis for this report. Results: Partial response (PR) occurred in two of 44 patients (5%; 95% confidence interval, 1% to 15%) receiving IL-2 alone, compared with four of 41 patients (10%; 95% confidence interval, 3% to 23%) receiving IL-2/IFN-α (P = .30). There were no complete responses (CRs). The median duration of response was 11.5 months (range, 2.0 to 15.7+). There was no significant difference in the median survival duration for patients receiving IL-2 alone (10.2 months) compared with patients receiving IL-2/IFN-α (9.7 months). The median and mean number of doses of IL-2 were equivalent in both groups, as was toxicity. There were three treatment-related deaths, two in the IL-2-alone arm and one in the IL-2/IFN-α arm. The trial was terminated after the first interim analysis based on predefined early-stopping rules, which included termination if the response rate in the IL-2/IFN-α arm was less than 25%. Conclusion: Using the preparation, dose, and schedule of IL-2 in our trial, IFN-α failed to enhance significantly the response rate to high-dose IL-2 in the treatment of patients with advanced melanoma.

Original languageEnglish (US)
Pages (from-to)1969-1977
Number of pages9
JournalJournal of Clinical Oncology
Volume11
Issue number10
StatePublished - 1993

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Interleukin-2
Melanoma
Therapeutics
interferon alfa-2a
Appointments and Schedules
Confidence Intervals
Interleukin-6
Survival Rate

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma. / Sparano, Joseph A.; Fisher, Richard I.; Sunderland, Margaret; Margolin, Kim; Ernest, Mary Lou; Sznol, Mario; Atkins, Michael B.; Dutcher, Janice P.; Micetich, Kenneth C.; Weiss, Geoffrey R.; Doroshow, James H.; Aronson, Frederick R.; Rubinstein, Lawrence V.; Mier, James W.

In: Journal of Clinical Oncology, Vol. 11, No. 10, 1993, p. 1969-1977.

Research output: Contribution to journalArticle

Sparano, JA, Fisher, RI, Sunderland, M, Margolin, K, Ernest, ML, Sznol, M, Atkins, MB, Dutcher, JP, Micetich, KC, Weiss, GR, Doroshow, JH, Aronson, FR, Rubinstein, LV & Mier, JW 1993, 'Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma', Journal of Clinical Oncology, vol. 11, no. 10, pp. 1969-1977.
Sparano, Joseph A. ; Fisher, Richard I. ; Sunderland, Margaret ; Margolin, Kim ; Ernest, Mary Lou ; Sznol, Mario ; Atkins, Michael B. ; Dutcher, Janice P. ; Micetich, Kenneth C. ; Weiss, Geoffrey R. ; Doroshow, James H. ; Aronson, Frederick R. ; Rubinstein, Lawrence V. ; Mier, James W. / Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma. In: Journal of Clinical Oncology. 1993 ; Vol. 11, No. 10. pp. 1969-1977.
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title = "Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma",
abstract = "Purpose: To compare the response rate, survival, and toxicity of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus interferon alfa-2a (IFN-α) with high-dose IL-2 alone in patients with advanced melanoma in a randomized phase III trial design. Patients and Methods: Eighty-five patients with advanced melanoma were randomly assigned to receive IL-2 6 × 106 U/m2 per dose every 8 hours as tolerated for a maximum of 14 doses on days 1 through 5 and 15 through 19, or IL-2 4.5 × 106 U/m2 per dose, plus IFN-α 3 × 106 U/m2 using an identical schedule. A planned interim analysis was performed after 85 patients were entered, which forms the basis for this report. Results: Partial response (PR) occurred in two of 44 patients (5{\%}; 95{\%} confidence interval, 1{\%} to 15{\%}) receiving IL-2 alone, compared with four of 41 patients (10{\%}; 95{\%} confidence interval, 3{\%} to 23{\%}) receiving IL-2/IFN-α (P = .30). There were no complete responses (CRs). The median duration of response was 11.5 months (range, 2.0 to 15.7+). There was no significant difference in the median survival duration for patients receiving IL-2 alone (10.2 months) compared with patients receiving IL-2/IFN-α (9.7 months). The median and mean number of doses of IL-2 were equivalent in both groups, as was toxicity. There were three treatment-related deaths, two in the IL-2-alone arm and one in the IL-2/IFN-α arm. The trial was terminated after the first interim analysis based on predefined early-stopping rules, which included termination if the response rate in the IL-2/IFN-α arm was less than 25{\%}. Conclusion: Using the preparation, dose, and schedule of IL-2 in our trial, IFN-α failed to enhance significantly the response rate to high-dose IL-2 in the treatment of patients with advanced melanoma.",
author = "Sparano, {Joseph A.} and Fisher, {Richard I.} and Margaret Sunderland and Kim Margolin and Ernest, {Mary Lou} and Mario Sznol and Atkins, {Michael B.} and Dutcher, {Janice P.} and Micetich, {Kenneth C.} and Weiss, {Geoffrey R.} and Doroshow, {James H.} and Aronson, {Frederick R.} and Rubinstein, {Lawrence V.} and Mier, {James W.}",
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T1 - Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma

AU - Sparano, Joseph A.

AU - Fisher, Richard I.

AU - Sunderland, Margaret

AU - Margolin, Kim

AU - Ernest, Mary Lou

AU - Sznol, Mario

AU - Atkins, Michael B.

AU - Dutcher, Janice P.

AU - Micetich, Kenneth C.

AU - Weiss, Geoffrey R.

AU - Doroshow, James H.

AU - Aronson, Frederick R.

AU - Rubinstein, Lawrence V.

AU - Mier, James W.

PY - 1993

Y1 - 1993

N2 - Purpose: To compare the response rate, survival, and toxicity of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus interferon alfa-2a (IFN-α) with high-dose IL-2 alone in patients with advanced melanoma in a randomized phase III trial design. Patients and Methods: Eighty-five patients with advanced melanoma were randomly assigned to receive IL-2 6 × 106 U/m2 per dose every 8 hours as tolerated for a maximum of 14 doses on days 1 through 5 and 15 through 19, or IL-2 4.5 × 106 U/m2 per dose, plus IFN-α 3 × 106 U/m2 using an identical schedule. A planned interim analysis was performed after 85 patients were entered, which forms the basis for this report. Results: Partial response (PR) occurred in two of 44 patients (5%; 95% confidence interval, 1% to 15%) receiving IL-2 alone, compared with four of 41 patients (10%; 95% confidence interval, 3% to 23%) receiving IL-2/IFN-α (P = .30). There were no complete responses (CRs). The median duration of response was 11.5 months (range, 2.0 to 15.7+). There was no significant difference in the median survival duration for patients receiving IL-2 alone (10.2 months) compared with patients receiving IL-2/IFN-α (9.7 months). The median and mean number of doses of IL-2 were equivalent in both groups, as was toxicity. There were three treatment-related deaths, two in the IL-2-alone arm and one in the IL-2/IFN-α arm. The trial was terminated after the first interim analysis based on predefined early-stopping rules, which included termination if the response rate in the IL-2/IFN-α arm was less than 25%. Conclusion: Using the preparation, dose, and schedule of IL-2 in our trial, IFN-α failed to enhance significantly the response rate to high-dose IL-2 in the treatment of patients with advanced melanoma.

AB - Purpose: To compare the response rate, survival, and toxicity of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus interferon alfa-2a (IFN-α) with high-dose IL-2 alone in patients with advanced melanoma in a randomized phase III trial design. Patients and Methods: Eighty-five patients with advanced melanoma were randomly assigned to receive IL-2 6 × 106 U/m2 per dose every 8 hours as tolerated for a maximum of 14 doses on days 1 through 5 and 15 through 19, or IL-2 4.5 × 106 U/m2 per dose, plus IFN-α 3 × 106 U/m2 using an identical schedule. A planned interim analysis was performed after 85 patients were entered, which forms the basis for this report. Results: Partial response (PR) occurred in two of 44 patients (5%; 95% confidence interval, 1% to 15%) receiving IL-2 alone, compared with four of 41 patients (10%; 95% confidence interval, 3% to 23%) receiving IL-2/IFN-α (P = .30). There were no complete responses (CRs). The median duration of response was 11.5 months (range, 2.0 to 15.7+). There was no significant difference in the median survival duration for patients receiving IL-2 alone (10.2 months) compared with patients receiving IL-2/IFN-α (9.7 months). The median and mean number of doses of IL-2 were equivalent in both groups, as was toxicity. There were three treatment-related deaths, two in the IL-2-alone arm and one in the IL-2/IFN-α arm. The trial was terminated after the first interim analysis based on predefined early-stopping rules, which included termination if the response rate in the IL-2/IFN-α arm was less than 25%. Conclusion: Using the preparation, dose, and schedule of IL-2 in our trial, IFN-α failed to enhance significantly the response rate to high-dose IL-2 in the treatment of patients with advanced melanoma.

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