Phase I study of cancer therapy with recombinant interleukin-2 administered by intravenous bolus injection

Evan M Hersh, J. Lee Murray, Waun Ki Hong, Michael G. Rosenblum, James M. Reuben, Robert Weilbaecher, Amar N. Sarwal, Edward C. Bradley, Michael Konrad, Frank C. Arnett

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Sixty-six patients with disseminated malignancy were treated with recombinant interleukin-2 (IL-2) on a three times a week (M, W, F) IV-bolus injection schedule. Doses ranged from 0.001 to 14.0 × 106 units/M2 body surface area. Consecutive groups of 3-5 patients were placed on each dose level and were maintained on that level except for dosage de-escalation for toxicity. Toxicity to all major organ systems were noted with major toxicity including fever and chills, anorexia, fatigue and malaise, arthralgias and arthritis as well as hepatic and renal toxicity. All toxicity reversed within one week of drug cessation. Renal toxicity manifested by azotemia, arthritis and fatigue were the common dose limiting toxicities and the maximally tolerated dose was 12 × 106 units/M2. Pharmacokinetic studies indicated a short half-life (T 1/2 α = 7-23 minutes). At doses over 0.5 × 106 units/M2 increases in absolute lymphocytes and eosinophil counts were noted. All T lymphocyte subsets increased. Maximal increases were seen at 4-8 × 106 units/M2 with a lesser increase at 10-14 × 106 units/M2 dosage level. Circulating NK cells also increased while circulating LAK cells were detected during therapy. Partial responses were noted in 3 patients with melanoma. These lasted 4, 6 and 16 months and involved pulmonary, pulmonary plus mesenteric and retro-orbital plus hepatic metastases respectively in these patients.

Original languageEnglish (US)
Pages (from-to)215-226
Number of pages12
JournalBiotherapy
Volume1
Issue number3
DOIs
StatePublished - Sep 1989
Externally publishedYes

Fingerprint

Intravenous Injections
Interleukin-2
Arthritis
Fatigue
Neoplasms
Azotemia
Kidney
Lymphokine-Activated Killer Cells
Chills
Lung
Maximum Tolerated Dose
Body Surface Area
Liver
Arthralgia
Lymphocyte Count
Anorexia
T-Lymphocyte Subsets
Therapeutics
Eosinophils
Natural Killer Cells

ASJC Scopus subject areas

  • Pharmacology

Cite this

Hersh, E. M., Lee Murray, J., Ki Hong, W., Rosenblum, M. G., Reuben, J. M., Weilbaecher, R., ... Arnett, F. C. (1989). Phase I study of cancer therapy with recombinant interleukin-2 administered by intravenous bolus injection. Biotherapy, 1(3), 215-226. https://doi.org/10.1007/BF02170890

Phase I study of cancer therapy with recombinant interleukin-2 administered by intravenous bolus injection. / Hersh, Evan M; Lee Murray, J.; Ki Hong, Waun; Rosenblum, Michael G.; Reuben, James M.; Weilbaecher, Robert; Sarwal, Amar N.; Bradley, Edward C.; Konrad, Michael; Arnett, Frank C.

In: Biotherapy, Vol. 1, No. 3, 09.1989, p. 215-226.

Research output: Contribution to journalArticle

Hersh, EM, Lee Murray, J, Ki Hong, W, Rosenblum, MG, Reuben, JM, Weilbaecher, R, Sarwal, AN, Bradley, EC, Konrad, M & Arnett, FC 1989, 'Phase I study of cancer therapy with recombinant interleukin-2 administered by intravenous bolus injection', Biotherapy, vol. 1, no. 3, pp. 215-226. https://doi.org/10.1007/BF02170890
Hersh, Evan M ; Lee Murray, J. ; Ki Hong, Waun ; Rosenblum, Michael G. ; Reuben, James M. ; Weilbaecher, Robert ; Sarwal, Amar N. ; Bradley, Edward C. ; Konrad, Michael ; Arnett, Frank C. / Phase I study of cancer therapy with recombinant interleukin-2 administered by intravenous bolus injection. In: Biotherapy. 1989 ; Vol. 1, No. 3. pp. 215-226.
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