Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells

A phase II clinical trial

R. I. Fisher, C. A. Coltman, J. H. Doroshow, A. A. Rayner, M. J. Hawkins, J. W. Mier, P. Wiernik, J. D. McMannis, G. R. Weiss, K. A. Margolin, B. T. Gemlo, D. F. Hoth, D. R. Parkinson, Elisabeth M. Paietta

Research output: Contribution to journalArticle

325 Citations (Scopus)

Abstract

Study Objective: To confirm the antitumor efficacy of treatment with interleukin-2 and lymphokine-activated killer cells in patients with metastatic renal cancer. Design: Nonrandomized, phase II clinical trial. Setting: Tertiary care units in university medical centers. Patients: Consecutive trial of 35 patients with metastatic or unresectable renal cell cancer who have bidimensionally measurable disease, performance status 0 or 1, and normal function of all vital organs. Thirty-two patients completed interleukin-2 priming and received at least one lymphokine-activated killer cell infusion. Three patients were removed from the study and did not receive infusion of cells secondary to rapid tumor progression or toxicity. Interventions: Patients initially received recombinant interleukin-2, 100 000 units/kg body weight every 8 hours, on days 1 to 5 in a priming phase to stimulate lymphokine-activated killer cell precursors and effector activity in vivo. Leukapheresis was done on days 8 to 12 and lymphocytes were cultured in vitro with interleukin-2 for 3 to 4 days to amplify lymphokine-activated killer cell activity. Finally, interleukin-2, 100 000 units/kg every 8 hours, was infused with cultured cells on days 12 to 16. All doses of interleukin-2 and lymphokine-activated killer cells were administered in intensive care units. Measurements and Main Results: The mean number of doses of interleukin-2 administered during the priming phase was 12.9 ± 0.4; the mean number of lymphokine-activated killer cells reinfused was 7.0 ± 0.6 x 1010; and the mean number of interleukin-2 doses administered during the last phase was 10.2 ± 0.6. The overall objective response rate was 16%; two patients had complete responses and three patients had partial responses with greater than 50% reduction of all measurable tumor. The complete responders remain disease-free at 12 and 9 months. Two partial responders have not had tumor regrowth at 16 and 15 months. The third partial responder relapsed at 4 months. Toxicity was severe but generally of short duration and manageable. There were no treatment-related deaths. Hypotension, weight gain, anemia, and elevations of serum creatinine levels and liver enzymes were common. Two patients required intubation; one patient had a myocardial infarction. Conclusions: This phase II study confirms the antitumor activity of interleukin-2 and lymphokine-activated killer cell therapy in patients with metastatic or unresectable renal cell cancer. Response rates, especially complete remission rates, are comparable or better than rates achieved with other forms of therapy.

Original languageEnglish (US)
Pages (from-to)518-523
Number of pages6
JournalAnnals of Internal Medicine
Volume108
Issue number4
StatePublished - 1988
Externally publishedYes

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Lymphokine-Activated Killer Cells
Phase II Clinical Trials
Kidney Neoplasms
Interleukin-2
Renal Cell Carcinoma
Leukapheresis
Neoplasms
Interleukin-3
Tertiary Healthcare
Cell- and Tissue-Based Therapy
Intubation
Hypotension
Weight Gain
Intensive Care Units
Anemia
Cultured Cells
Creatinine
Myocardial Infarction
Body Weight

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fisher, R. I., Coltman, C. A., Doroshow, J. H., Rayner, A. A., Hawkins, M. J., Mier, J. W., ... Paietta, E. M. (1988). Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells: A phase II clinical trial. Annals of Internal Medicine, 108(4), 518-523.

Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells : A phase II clinical trial. / Fisher, R. I.; Coltman, C. A.; Doroshow, J. H.; Rayner, A. A.; Hawkins, M. J.; Mier, J. W.; Wiernik, P.; McMannis, J. D.; Weiss, G. R.; Margolin, K. A.; Gemlo, B. T.; Hoth, D. F.; Parkinson, D. R.; Paietta, Elisabeth M.

In: Annals of Internal Medicine, Vol. 108, No. 4, 1988, p. 518-523.

Research output: Contribution to journalArticle

Fisher, RI, Coltman, CA, Doroshow, JH, Rayner, AA, Hawkins, MJ, Mier, JW, Wiernik, P, McMannis, JD, Weiss, GR, Margolin, KA, Gemlo, BT, Hoth, DF, Parkinson, DR & Paietta, EM 1988, 'Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells: A phase II clinical trial', Annals of Internal Medicine, vol. 108, no. 4, pp. 518-523.
Fisher RI, Coltman CA, Doroshow JH, Rayner AA, Hawkins MJ, Mier JW et al. Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells: A phase II clinical trial. Annals of Internal Medicine. 1988;108(4):518-523.
Fisher, R. I. ; Coltman, C. A. ; Doroshow, J. H. ; Rayner, A. A. ; Hawkins, M. J. ; Mier, J. W. ; Wiernik, P. ; McMannis, J. D. ; Weiss, G. R. ; Margolin, K. A. ; Gemlo, B. T. ; Hoth, D. F. ; Parkinson, D. R. ; Paietta, Elisabeth M. / Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells : A phase II clinical trial. In: Annals of Internal Medicine. 1988 ; Vol. 108, No. 4. pp. 518-523.
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title = "Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells: A phase II clinical trial",
abstract = "Study Objective: To confirm the antitumor efficacy of treatment with interleukin-2 and lymphokine-activated killer cells in patients with metastatic renal cancer. Design: Nonrandomized, phase II clinical trial. Setting: Tertiary care units in university medical centers. Patients: Consecutive trial of 35 patients with metastatic or unresectable renal cell cancer who have bidimensionally measurable disease, performance status 0 or 1, and normal function of all vital organs. Thirty-two patients completed interleukin-2 priming and received at least one lymphokine-activated killer cell infusion. Three patients were removed from the study and did not receive infusion of cells secondary to rapid tumor progression or toxicity. Interventions: Patients initially received recombinant interleukin-2, 100 000 units/kg body weight every 8 hours, on days 1 to 5 in a priming phase to stimulate lymphokine-activated killer cell precursors and effector activity in vivo. Leukapheresis was done on days 8 to 12 and lymphocytes were cultured in vitro with interleukin-2 for 3 to 4 days to amplify lymphokine-activated killer cell activity. Finally, interleukin-2, 100 000 units/kg every 8 hours, was infused with cultured cells on days 12 to 16. All doses of interleukin-2 and lymphokine-activated killer cells were administered in intensive care units. Measurements and Main Results: The mean number of doses of interleukin-2 administered during the priming phase was 12.9 ± 0.4; the mean number of lymphokine-activated killer cells reinfused was 7.0 ± 0.6 x 1010; and the mean number of interleukin-2 doses administered during the last phase was 10.2 ± 0.6. The overall objective response rate was 16{\%}; two patients had complete responses and three patients had partial responses with greater than 50{\%} reduction of all measurable tumor. The complete responders remain disease-free at 12 and 9 months. Two partial responders have not had tumor regrowth at 16 and 15 months. The third partial responder relapsed at 4 months. Toxicity was severe but generally of short duration and manageable. There were no treatment-related deaths. Hypotension, weight gain, anemia, and elevations of serum creatinine levels and liver enzymes were common. Two patients required intubation; one patient had a myocardial infarction. Conclusions: This phase II study confirms the antitumor activity of interleukin-2 and lymphokine-activated killer cell therapy in patients with metastatic or unresectable renal cell cancer. Response rates, especially complete remission rates, are comparable or better than rates achieved with other forms of therapy.",
author = "Fisher, {R. I.} and Coltman, {C. A.} and Doroshow, {J. H.} and Rayner, {A. A.} and Hawkins, {M. J.} and Mier, {J. W.} and P. Wiernik and McMannis, {J. D.} and Weiss, {G. R.} and Margolin, {K. A.} and Gemlo, {B. T.} and Hoth, {D. F.} and Parkinson, {D. R.} and Paietta, {Elisabeth M.}",
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TY - JOUR

T1 - Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells

T2 - A phase II clinical trial

AU - Fisher, R. I.

AU - Coltman, C. A.

AU - Doroshow, J. H.

AU - Rayner, A. A.

AU - Hawkins, M. J.

AU - Mier, J. W.

AU - Wiernik, P.

AU - McMannis, J. D.

AU - Weiss, G. R.

AU - Margolin, K. A.

AU - Gemlo, B. T.

AU - Hoth, D. F.

AU - Parkinson, D. R.

AU - Paietta, Elisabeth M.

PY - 1988

Y1 - 1988

N2 - Study Objective: To confirm the antitumor efficacy of treatment with interleukin-2 and lymphokine-activated killer cells in patients with metastatic renal cancer. Design: Nonrandomized, phase II clinical trial. Setting: Tertiary care units in university medical centers. Patients: Consecutive trial of 35 patients with metastatic or unresectable renal cell cancer who have bidimensionally measurable disease, performance status 0 or 1, and normal function of all vital organs. Thirty-two patients completed interleukin-2 priming and received at least one lymphokine-activated killer cell infusion. Three patients were removed from the study and did not receive infusion of cells secondary to rapid tumor progression or toxicity. Interventions: Patients initially received recombinant interleukin-2, 100 000 units/kg body weight every 8 hours, on days 1 to 5 in a priming phase to stimulate lymphokine-activated killer cell precursors and effector activity in vivo. Leukapheresis was done on days 8 to 12 and lymphocytes were cultured in vitro with interleukin-2 for 3 to 4 days to amplify lymphokine-activated killer cell activity. Finally, interleukin-2, 100 000 units/kg every 8 hours, was infused with cultured cells on days 12 to 16. All doses of interleukin-2 and lymphokine-activated killer cells were administered in intensive care units. Measurements and Main Results: The mean number of doses of interleukin-2 administered during the priming phase was 12.9 ± 0.4; the mean number of lymphokine-activated killer cells reinfused was 7.0 ± 0.6 x 1010; and the mean number of interleukin-2 doses administered during the last phase was 10.2 ± 0.6. The overall objective response rate was 16%; two patients had complete responses and three patients had partial responses with greater than 50% reduction of all measurable tumor. The complete responders remain disease-free at 12 and 9 months. Two partial responders have not had tumor regrowth at 16 and 15 months. The third partial responder relapsed at 4 months. Toxicity was severe but generally of short duration and manageable. There were no treatment-related deaths. Hypotension, weight gain, anemia, and elevations of serum creatinine levels and liver enzymes were common. Two patients required intubation; one patient had a myocardial infarction. Conclusions: This phase II study confirms the antitumor activity of interleukin-2 and lymphokine-activated killer cell therapy in patients with metastatic or unresectable renal cell cancer. Response rates, especially complete remission rates, are comparable or better than rates achieved with other forms of therapy.

AB - Study Objective: To confirm the antitumor efficacy of treatment with interleukin-2 and lymphokine-activated killer cells in patients with metastatic renal cancer. Design: Nonrandomized, phase II clinical trial. Setting: Tertiary care units in university medical centers. Patients: Consecutive trial of 35 patients with metastatic or unresectable renal cell cancer who have bidimensionally measurable disease, performance status 0 or 1, and normal function of all vital organs. Thirty-two patients completed interleukin-2 priming and received at least one lymphokine-activated killer cell infusion. Three patients were removed from the study and did not receive infusion of cells secondary to rapid tumor progression or toxicity. Interventions: Patients initially received recombinant interleukin-2, 100 000 units/kg body weight every 8 hours, on days 1 to 5 in a priming phase to stimulate lymphokine-activated killer cell precursors and effector activity in vivo. Leukapheresis was done on days 8 to 12 and lymphocytes were cultured in vitro with interleukin-2 for 3 to 4 days to amplify lymphokine-activated killer cell activity. Finally, interleukin-2, 100 000 units/kg every 8 hours, was infused with cultured cells on days 12 to 16. All doses of interleukin-2 and lymphokine-activated killer cells were administered in intensive care units. Measurements and Main Results: The mean number of doses of interleukin-2 administered during the priming phase was 12.9 ± 0.4; the mean number of lymphokine-activated killer cells reinfused was 7.0 ± 0.6 x 1010; and the mean number of interleukin-2 doses administered during the last phase was 10.2 ± 0.6. The overall objective response rate was 16%; two patients had complete responses and three patients had partial responses with greater than 50% reduction of all measurable tumor. The complete responders remain disease-free at 12 and 9 months. Two partial responders have not had tumor regrowth at 16 and 15 months. The third partial responder relapsed at 4 months. Toxicity was severe but generally of short duration and manageable. There were no treatment-related deaths. Hypotension, weight gain, anemia, and elevations of serum creatinine levels and liver enzymes were common. Two patients required intubation; one patient had a myocardial infarction. Conclusions: This phase II study confirms the antitumor activity of interleukin-2 and lymphokine-activated killer cell therapy in patients with metastatic or unresectable renal cell cancer. Response rates, especially complete remission rates, are comparable or better than rates achieved with other forms of therapy.

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