A phase I study of high-dose interleukin-2 in combination with interferon-α<inf>2b</inf>

Mario Sznol, James W. Mier, Joseph A. Sparano, Ellen R. Gaynor, Geoffrey R. Weiss, Kim A. Margolin, Michael H. Bar, Michael J. Hawkins, Michael B. Atkins, Janice P. Dutcher, Richard I. Fisher, David H. Boldt, James H. Doroshow, Arthur Louie, Frederick R. Aronson

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Our group and others have conducted phase II trials of high-dose interleukin-2 (IL-2) or IL-2 with the adoptive transfer of in vitro activated lymphocytes in patients with advanced malignancies. Although durable complete and partial responses were seen in patients with renal cell carcinoma and metastatic melanoma, overall response rates were low and toxicity was substantial. In preclinical models, the combination of IL-2 and interferon-α has synergistic antitumor activity. Based on these data, and our prior experience with high-dose IL-2 (Cetus), we conducted a trial to determine the maximum tolerated dose of IL-2 (0.4, 0.8, and 1.2 mg/m<sup>2</sup>) administered together with a fixed dose of interferon-α<inf>2b</inf> (3 × 10<sup>6</sup> u/m<sup>2</sup>) intravenously every 8 h on days 1-5 and 15-19. Patients were monitored in the intensive care unit and given pressor support for hypotension as needed. Twenty-four patients were entered (6, 10, and 8 at each IL-2 dose, respectively; 14 renal cell carcinoma, 7 melanoma, 2 colon, and 1 hepatoma). The median age was 56 years, the male to female ratio was 19:5, and performance status was 0 or 1 (Eastern Cooperative Oncology Group) in all patients. Toxicity was similar at all dose levels, but the onset was earlier in the treatment course as the dose of IL-2 was escalated in successive cohorts; therefore, more doses were withheld at the higher dose levels. The major toxicities resulting in the interruption or stopping of treatment were hypotension requiring pressors, dyspnea, and neurotoxicity. Grade 1 or 2 fever, nausea and vomiting, fatigue, and cutaneous reactions were common at all dose levels. Reversible grade 3 or 4 transaminase elevations were also seen in most patients, but were not considered dose limiting. Three objective responses were noted in patients with renal cell carcinoma: one at dose level 2 and two at dose level 3. Dose level 2 was chosen for further phase II evaluation.

Original languageEnglish (US)
Pages (from-to)529-537
Number of pages9
JournalJournal of Biological Response Modifiers
Volume9
Issue number6
StatePublished - 1990

Fingerprint

Interferons
Interleukin-2
Renal Cell Carcinoma
Hypotension
Melanoma
Maximum Tolerated Dose
Adoptive Transfer
Transaminases
Dyspnea
Nausea
Vomiting
Fatigue
Intensive Care Units
Hepatocellular Carcinoma
Colon
Fever
Lymphocytes
Skin
Therapeutics
Neoplasms

Keywords

  • Advanced malignancies
  • Interferon-α<inf>2b</inf>
  • Interleukin-2
  • Phase I trial

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Pharmacology

Cite this

Sznol, M., Mier, J. W., Sparano, J. A., Gaynor, E. R., Weiss, G. R., Margolin, K. A., ... Aronson, F. R. (1990). A phase I study of high-dose interleukin-2 in combination with interferon-α<inf>2b</inf> . Journal of Biological Response Modifiers, 9(6), 529-537.

A phase I study of high-dose interleukin-2 in combination with interferon-α<inf>2b</inf> . / Sznol, Mario; Mier, James W.; Sparano, Joseph A.; Gaynor, Ellen R.; Weiss, Geoffrey R.; Margolin, Kim A.; Bar, Michael H.; Hawkins, Michael J.; Atkins, Michael B.; Dutcher, Janice P.; Fisher, Richard I.; Boldt, David H.; Doroshow, James H.; Louie, Arthur; Aronson, Frederick R.

In: Journal of Biological Response Modifiers, Vol. 9, No. 6, 1990, p. 529-537.

Research output: Contribution to journalArticle

Sznol, M, Mier, JW, Sparano, JA, Gaynor, ER, Weiss, GR, Margolin, KA, Bar, MH, Hawkins, MJ, Atkins, MB, Dutcher, JP, Fisher, RI, Boldt, DH, Doroshow, JH, Louie, A & Aronson, FR 1990, 'A phase I study of high-dose interleukin-2 in combination with interferon-α<inf>2b</inf> ', Journal of Biological Response Modifiers, vol. 9, no. 6, pp. 529-537.
Sznol, Mario ; Mier, James W. ; Sparano, Joseph A. ; Gaynor, Ellen R. ; Weiss, Geoffrey R. ; Margolin, Kim A. ; Bar, Michael H. ; Hawkins, Michael J. ; Atkins, Michael B. ; Dutcher, Janice P. ; Fisher, Richard I. ; Boldt, David H. ; Doroshow, James H. ; Louie, Arthur ; Aronson, Frederick R. / A phase I study of high-dose interleukin-2 in combination with interferon-α<inf>2b</inf> . In: Journal of Biological Response Modifiers. 1990 ; Vol. 9, No. 6. pp. 529-537.
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AU - Mier, James W.

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AU - Weiss, Geoffrey R.

AU - Margolin, Kim A.

AU - Bar, Michael H.

AU - Hawkins, Michael J.

AU - Atkins, Michael B.

AU - Dutcher, Janice P.

AU - Fisher, Richard I.

AU - Boldt, David H.

AU - Doroshow, James H.

AU - Louie, Arthur

AU - Aronson, Frederick R.

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