Phase II studies of recombinant human interleukin-4 in advanced renal cancer and malignant melanoma

Kim Margolin, Frederick R. Aronson, Mario Sznol, Michael B. Atkins, Rasim A. Gucalp, Richard I. Fisher, Margaret Sunderland, James H. Doroshow, Mary Lou Ernest, James W. Mier, Janice P. Dutcher, Ellen R. Gaynor, Geoffrey R. Weiss

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Interleukin (IL)-4 is a pluripotent cytokine that stimulates proliferation of activated T-cells and has antineoplastic activity against human renal tumors in animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20 µg/kg, with dose-limiting toxicities consisting of fever, fluid retention, nasal congestion, and mucositis. We report the results of two separate Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19 patients with advanced renal cancer. IL-4 was administered intravenously every 8 h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27 patients were treated at a dose of 800 µg/m<sup>2</sup>, but after three of these patients developed cardiac toxicities, the dose was decreased to 600 µg/m<sup>2</sup>. One complete response occurred in a patient with metastatic melanoma (duration >30 months). No responses were seen among the patients with renal cancer. The most frequent side effects were fever, nausea, malaise, nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were also common. Hypotension was infrequent, but transient weight gain due to fluid retention was common. The major life-threatening toxicities were cardiac and gastrointestinal. Suspected cardiac ischemia was observed in two patients, pericarditis in one, and arrhythmias in two. Three patients had major upper gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4, when given as a single agent on this schedule at maximum tolerated dose, does not possess meaningful activity in renal cancer or melanoma.

Original languageEnglish (US)
Pages (from-to)147-153
Number of pages7
JournalJournal of Immunotherapy
Volume15
Issue number2
StatePublished - 1994

Fingerprint

Kidney Neoplasms
Interleukin-4
Melanoma
Nose
Fever
Kidney
Mucositis
Pericarditis
Maximum Tolerated Dose
Human Activities
Antineoplastic Agents
Hypotension
Nausea
Weight Gain
Cardiac Arrhythmias
Diarrhea
Neoplasms
Appointments and Schedules
Ischemia
Hemorrhage

Keywords

  • Cytokines
  • Immunotherapy
  • Interleukin-4
  • Malignant melanoma
  • Renal cancer

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

Margolin, K., Aronson, F. R., Sznol, M., Atkins, M. B., Gucalp, R. A., Fisher, R. I., ... Weiss, G. R. (1994). Phase II studies of recombinant human interleukin-4 in advanced renal cancer and malignant melanoma. Journal of Immunotherapy, 15(2), 147-153.

Phase II studies of recombinant human interleukin-4 in advanced renal cancer and malignant melanoma. / Margolin, Kim; Aronson, Frederick R.; Sznol, Mario; Atkins, Michael B.; Gucalp, Rasim A.; Fisher, Richard I.; Sunderland, Margaret; Doroshow, James H.; Ernest, Mary Lou; Mier, James W.; Dutcher, Janice P.; Gaynor, Ellen R.; Weiss, Geoffrey R.

In: Journal of Immunotherapy, Vol. 15, No. 2, 1994, p. 147-153.

Research output: Contribution to journalArticle

Margolin, K, Aronson, FR, Sznol, M, Atkins, MB, Gucalp, RA, Fisher, RI, Sunderland, M, Doroshow, JH, Ernest, ML, Mier, JW, Dutcher, JP, Gaynor, ER & Weiss, GR 1994, 'Phase II studies of recombinant human interleukin-4 in advanced renal cancer and malignant melanoma', Journal of Immunotherapy, vol. 15, no. 2, pp. 147-153.
Margolin, Kim ; Aronson, Frederick R. ; Sznol, Mario ; Atkins, Michael B. ; Gucalp, Rasim A. ; Fisher, Richard I. ; Sunderland, Margaret ; Doroshow, James H. ; Ernest, Mary Lou ; Mier, James W. ; Dutcher, Janice P. ; Gaynor, Ellen R. ; Weiss, Geoffrey R. / Phase II studies of recombinant human interleukin-4 in advanced renal cancer and malignant melanoma. In: Journal of Immunotherapy. 1994 ; Vol. 15, No. 2. pp. 147-153.
@article{38533d9a11e64cf687212fd3a7705ee0,
title = "Phase II studies of recombinant human interleukin-4 in advanced renal cancer and malignant melanoma",
abstract = "Interleukin (IL)-4 is a pluripotent cytokine that stimulates proliferation of activated T-cells and has antineoplastic activity against human renal tumors in animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20 µg/kg, with dose-limiting toxicities consisting of fever, fluid retention, nasal congestion, and mucositis. We report the results of two separate Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19 patients with advanced renal cancer. IL-4 was administered intravenously every 8 h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27 patients were treated at a dose of 800 µg/m2, but after three of these patients developed cardiac toxicities, the dose was decreased to 600 µg/m2. One complete response occurred in a patient with metastatic melanoma (duration >30 months). No responses were seen among the patients with renal cancer. The most frequent side effects were fever, nausea, malaise, nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were also common. Hypotension was infrequent, but transient weight gain due to fluid retention was common. The major life-threatening toxicities were cardiac and gastrointestinal. Suspected cardiac ischemia was observed in two patients, pericarditis in one, and arrhythmias in two. Three patients had major upper gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4, when given as a single agent on this schedule at maximum tolerated dose, does not possess meaningful activity in renal cancer or melanoma.",
keywords = "Cytokines, Immunotherapy, Interleukin-4, Malignant melanoma, Renal cancer",
author = "Kim Margolin and Aronson, {Frederick R.} and Mario Sznol and Atkins, {Michael B.} and Gucalp, {Rasim A.} and Fisher, {Richard I.} and Margaret Sunderland and Doroshow, {James H.} and Ernest, {Mary Lou} and Mier, {James W.} and Dutcher, {Janice P.} and Gaynor, {Ellen R.} and Weiss, {Geoffrey R.}",
year = "1994",
language = "English (US)",
volume = "15",
pages = "147--153",
journal = "Journal of Immunotherapy",
issn = "1053-8550",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Phase II studies of recombinant human interleukin-4 in advanced renal cancer and malignant melanoma

AU - Margolin, Kim

AU - Aronson, Frederick R.

AU - Sznol, Mario

AU - Atkins, Michael B.

AU - Gucalp, Rasim A.

AU - Fisher, Richard I.

AU - Sunderland, Margaret

AU - Doroshow, James H.

AU - Ernest, Mary Lou

AU - Mier, James W.

AU - Dutcher, Janice P.

AU - Gaynor, Ellen R.

AU - Weiss, Geoffrey R.

PY - 1994

Y1 - 1994

N2 - Interleukin (IL)-4 is a pluripotent cytokine that stimulates proliferation of activated T-cells and has antineoplastic activity against human renal tumors in animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20 µg/kg, with dose-limiting toxicities consisting of fever, fluid retention, nasal congestion, and mucositis. We report the results of two separate Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19 patients with advanced renal cancer. IL-4 was administered intravenously every 8 h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27 patients were treated at a dose of 800 µg/m2, but after three of these patients developed cardiac toxicities, the dose was decreased to 600 µg/m2. One complete response occurred in a patient with metastatic melanoma (duration >30 months). No responses were seen among the patients with renal cancer. The most frequent side effects were fever, nausea, malaise, nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were also common. Hypotension was infrequent, but transient weight gain due to fluid retention was common. The major life-threatening toxicities were cardiac and gastrointestinal. Suspected cardiac ischemia was observed in two patients, pericarditis in one, and arrhythmias in two. Three patients had major upper gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4, when given as a single agent on this schedule at maximum tolerated dose, does not possess meaningful activity in renal cancer or melanoma.

AB - Interleukin (IL)-4 is a pluripotent cytokine that stimulates proliferation of activated T-cells and has antineoplastic activity against human renal tumors in animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20 µg/kg, with dose-limiting toxicities consisting of fever, fluid retention, nasal congestion, and mucositis. We report the results of two separate Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19 patients with advanced renal cancer. IL-4 was administered intravenously every 8 h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27 patients were treated at a dose of 800 µg/m2, but after three of these patients developed cardiac toxicities, the dose was decreased to 600 µg/m2. One complete response occurred in a patient with metastatic melanoma (duration >30 months). No responses were seen among the patients with renal cancer. The most frequent side effects were fever, nausea, malaise, nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were also common. Hypotension was infrequent, but transient weight gain due to fluid retention was common. The major life-threatening toxicities were cardiac and gastrointestinal. Suspected cardiac ischemia was observed in two patients, pericarditis in one, and arrhythmias in two. Three patients had major upper gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4, when given as a single agent on this schedule at maximum tolerated dose, does not possess meaningful activity in renal cancer or melanoma.

KW - Cytokines

KW - Immunotherapy

KW - Interleukin-4

KW - Malignant melanoma

KW - Renal cancer

UR - http://www.scopus.com/inward/record.url?scp=0028014562&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028014562&partnerID=8YFLogxK

M3 - Article

C2 - 8136948

AN - SCOPUS:0028014562

VL - 15

SP - 147

EP - 153

JO - Journal of Immunotherapy

JF - Journal of Immunotherapy

SN - 1053-8550

IS - 2

ER -