Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer

B. L. Gause, M. Sznol, W. C. Kopp, John Edward Janik, II W. Smith, R. G. Steis, W. J. Urba, W. Sharfman, R. G. Fenton, S. P. Creekmore, J. Holmlund, K. C. Conlon, L. A. VanderMolen, D. L. Longo

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Abstract

Purpose: Although high-dose interleukin-2 (IL-2) can produce durable remissions in a subset of responding patients with renal cell carcinoma (RCC), this occurs in the setting of significant toxicity. The purpose of this study is to define the maximum-tolerated dosage (MTD) of IL-2 and interferon alfa-2a (IFNα-2a) that can be administered chronically on an outpatient basis. Patients and Methods: Fifty-three patients with advanced cancer of variable histology with good prognostic features were treated in six cohorts. Patients in cohorts one through five received IL-2 (1.5 or 3.0 x 106 million units (mU)/m2) Monday through Friday and IFNα-2a (1.5 or 3 x 106 mU/m2) daily for a 4-week cycle. In cohort six, IFNα-2a was given three times a week. Immunologic monitoring, including serum levels of soluble IL-2 receptor (sIL-2R) and neopterin, flow cytometry, and natural killer cell (NK) activity, were measured. Patients were evaluated for toxicity, response, and survival. Results: Almost all patients developed grade I/II toxicities commonly associated with cytokine therapy. Symptoms were most severe with the first treatment of each week. Dose-limiting toxicities included grade III fatigue, hypotension, and creatinine elevations. The MTD was 1.5 mU/m2 daily x 5 given subcutaneously repeated weekly for IL-2 and 1.5 mU/m2 daily subcutaneously (dose level 3) for IFN. Six of 25 assessable patients with RCC (24%) achieved a partial response (PR), including four of eight patients who were previously untreated. There were no objective responses in patients with other tumors, including 12 melanoma patients. Conclusion: IL-2 and IFNα-2a can be given with tolerable toxicities on an outpatient basis and shows significant activity in patients with metastatic RCC.

Original languageEnglish (US)
Pages (from-to)2234-2241
Number of pages8
JournalJournal of Clinical Oncology
Volume14
Issue number8
DOIs
StatePublished - Jan 1 1996

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Interleukin-2
Neoplasms
Renal Cell Carcinoma
interferon alfa-2a
Outpatients
Neopterin
Immunologic Monitoring
Interleukin-2 Receptors
Natural Killer Cells
Hypotension
Fatigue
Melanoma
Creatinine
Histology
Flow Cytometry
Cytokines
Survival
Therapeutics
Serum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer. / Gause, B. L.; Sznol, M.; Kopp, W. C.; Janik, John Edward; Smith, II W.; Steis, R. G.; Urba, W. J.; Sharfman, W.; Fenton, R. G.; Creekmore, S. P.; Holmlund, J.; Conlon, K. C.; VanderMolen, L. A.; Longo, D. L.

In: Journal of Clinical Oncology, Vol. 14, No. 8, 01.01.1996, p. 2234-2241.

Research output: Contribution to journalArticle

Gause, BL, Sznol, M, Kopp, WC, Janik, JE, Smith, IIW, Steis, RG, Urba, WJ, Sharfman, W, Fenton, RG, Creekmore, SP, Holmlund, J, Conlon, KC, VanderMolen, LA & Longo, DL 1996, 'Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer', Journal of Clinical Oncology, vol. 14, no. 8, pp. 2234-2241. https://doi.org/10.1200/JCO.1996.14.8.2234
Gause, B. L. ; Sznol, M. ; Kopp, W. C. ; Janik, John Edward ; Smith, II W. ; Steis, R. G. ; Urba, W. J. ; Sharfman, W. ; Fenton, R. G. ; Creekmore, S. P. ; Holmlund, J. ; Conlon, K. C. ; VanderMolen, L. A. ; Longo, D. L. / Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer. In: Journal of Clinical Oncology. 1996 ; Vol. 14, No. 8. pp. 2234-2241.
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abstract = "Purpose: Although high-dose interleukin-2 (IL-2) can produce durable remissions in a subset of responding patients with renal cell carcinoma (RCC), this occurs in the setting of significant toxicity. The purpose of this study is to define the maximum-tolerated dosage (MTD) of IL-2 and interferon alfa-2a (IFNα-2a) that can be administered chronically on an outpatient basis. Patients and Methods: Fifty-three patients with advanced cancer of variable histology with good prognostic features were treated in six cohorts. Patients in cohorts one through five received IL-2 (1.5 or 3.0 x 106 million units (mU)/m2) Monday through Friday and IFNα-2a (1.5 or 3 x 106 mU/m2) daily for a 4-week cycle. In cohort six, IFNα-2a was given three times a week. Immunologic monitoring, including serum levels of soluble IL-2 receptor (sIL-2R) and neopterin, flow cytometry, and natural killer cell (NK) activity, were measured. Patients were evaluated for toxicity, response, and survival. Results: Almost all patients developed grade I/II toxicities commonly associated with cytokine therapy. Symptoms were most severe with the first treatment of each week. Dose-limiting toxicities included grade III fatigue, hypotension, and creatinine elevations. The MTD was 1.5 mU/m2 daily x 5 given subcutaneously repeated weekly for IL-2 and 1.5 mU/m2 daily subcutaneously (dose level 3) for IFN. Six of 25 assessable patients with RCC (24{\%}) achieved a partial response (PR), including four of eight patients who were previously untreated. There were no objective responses in patients with other tumors, including 12 melanoma patients. Conclusion: IL-2 and IFNα-2a can be given with tolerable toxicities on an outpatient basis and shows significant activity in patients with metastatic RCC.",
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T1 - Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer

AU - Gause, B. L.

AU - Sznol, M.

AU - Kopp, W. C.

AU - Janik, John Edward

AU - Smith, II W.

AU - Steis, R. G.

AU - Urba, W. J.

AU - Sharfman, W.

AU - Fenton, R. G.

AU - Creekmore, S. P.

AU - Holmlund, J.

AU - Conlon, K. C.

AU - VanderMolen, L. A.

AU - Longo, D. L.

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Y1 - 1996/1/1

N2 - Purpose: Although high-dose interleukin-2 (IL-2) can produce durable remissions in a subset of responding patients with renal cell carcinoma (RCC), this occurs in the setting of significant toxicity. The purpose of this study is to define the maximum-tolerated dosage (MTD) of IL-2 and interferon alfa-2a (IFNα-2a) that can be administered chronically on an outpatient basis. Patients and Methods: Fifty-three patients with advanced cancer of variable histology with good prognostic features were treated in six cohorts. Patients in cohorts one through five received IL-2 (1.5 or 3.0 x 106 million units (mU)/m2) Monday through Friday and IFNα-2a (1.5 or 3 x 106 mU/m2) daily for a 4-week cycle. In cohort six, IFNα-2a was given three times a week. Immunologic monitoring, including serum levels of soluble IL-2 receptor (sIL-2R) and neopterin, flow cytometry, and natural killer cell (NK) activity, were measured. Patients were evaluated for toxicity, response, and survival. Results: Almost all patients developed grade I/II toxicities commonly associated with cytokine therapy. Symptoms were most severe with the first treatment of each week. Dose-limiting toxicities included grade III fatigue, hypotension, and creatinine elevations. The MTD was 1.5 mU/m2 daily x 5 given subcutaneously repeated weekly for IL-2 and 1.5 mU/m2 daily subcutaneously (dose level 3) for IFN. Six of 25 assessable patients with RCC (24%) achieved a partial response (PR), including four of eight patients who were previously untreated. There were no objective responses in patients with other tumors, including 12 melanoma patients. Conclusion: IL-2 and IFNα-2a can be given with tolerable toxicities on an outpatient basis and shows significant activity in patients with metastatic RCC.

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