Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine-activated killer cells

M. H. Bar, M. Sznol, M. B. Atkins, N. Ciobanu, K. C. Micetich, D. H. Boldt, K. A. Margolin, F. R. Aronson, A. A. Rayner, M. J. Hawkins, J. W. Mier, Elisabeth M. Paietta, R. I. Fisher, G. R. Weiss, J. H. Doroshow

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Abstract

Fifty patients with advanced melanoma received high-dose bolus and continuous infusion interleukin-2 (IL-2) with lymphokine-activated killer (LAK) cells in an attempt to improve the therapeutic index of this active but toxic therapy. Treatment began with up to nine bolus doses of IL-2 administered over 3 days. After 1 day of rest, patients underwent daily leukapheresis for 4 days, and the leukocytes were cultured with IL-2 in vitro to prepare LAK cells. Continuous infusion IL-2 was begun 1 day after the last leukapheresis and continued for up to 148 hours; LAK cells were administered on days 1, 2, and 4 of the infusion. Responding patients were eligible to receive up to two additional cycles of therapy at 3-month intervals. Most patients completed each cycle without dose reduction. One patient had complete response and six patients had partial responses (14% response rate). The complete responder and three of the partial responders (8%) remain free from disease progression with follow-up of 21 to 24 months. Of these four patients with durable remissions, one had extensive liver and lymph node metastases, one had lymph node, pleural, and parenchymal lung metastases, and two had disease limited to lymph nodes or subcutaneous tissues. Seventeen patients (34%) required pressors for hypotension, three patients (6%) developed hemodynamically significant arrhythmias, and six patients (12%) developed dyspnea at rest, but none required intubation and there were no treatment-related deaths. Unacceptable toxicity developed in two patients during bolus IL-2 administration and therapy was aborted; both returned to baseline status within 4 days of discontinuing IL-2. Fever, oliguria, and elevated creatinine or transaminase levels occurred frequently but were also transient. Despite less frequent severe toxicity with this modified regimen, these results confirm the ability of IL-2 and LAK cell therapy to induce durable remissions in some patients with advanced melanoma.

Original languageEnglish (US)
Pages (from-to)1138-1147
Number of pages10
JournalJournal of Clinical Oncology
Volume8
Issue number7
StatePublished - 1990
Externally publishedYes

Fingerprint

Lymphokine-Activated Killer Cells
Interleukin-2
Melanoma
Leukapheresis
Lymph Nodes
Therapeutics
Neoplasm Metastasis
Oliguria
Poisons
Subcutaneous Tissue
Cell- and Tissue-Based Therapy
Transaminases
Intubation
Dyspnea
Hypotension
Disease Progression
Cardiac Arrhythmias
Creatinine
Leukocytes
Fever

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bar, M. H., Sznol, M., Atkins, M. B., Ciobanu, N., Micetich, K. C., Boldt, D. H., ... Doroshow, J. H. (1990). Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine-activated killer cells. Journal of Clinical Oncology, 8(7), 1138-1147.

Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine-activated killer cells. / Bar, M. H.; Sznol, M.; Atkins, M. B.; Ciobanu, N.; Micetich, K. C.; Boldt, D. H.; Margolin, K. A.; Aronson, F. R.; Rayner, A. A.; Hawkins, M. J.; Mier, J. W.; Paietta, Elisabeth M.; Fisher, R. I.; Weiss, G. R.; Doroshow, J. H.

In: Journal of Clinical Oncology, Vol. 8, No. 7, 1990, p. 1138-1147.

Research output: Contribution to journalArticle

Bar, MH, Sznol, M, Atkins, MB, Ciobanu, N, Micetich, KC, Boldt, DH, Margolin, KA, Aronson, FR, Rayner, AA, Hawkins, MJ, Mier, JW, Paietta, EM, Fisher, RI, Weiss, GR & Doroshow, JH 1990, 'Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine-activated killer cells', Journal of Clinical Oncology, vol. 8, no. 7, pp. 1138-1147.
Bar, M. H. ; Sznol, M. ; Atkins, M. B. ; Ciobanu, N. ; Micetich, K. C. ; Boldt, D. H. ; Margolin, K. A. ; Aronson, F. R. ; Rayner, A. A. ; Hawkins, M. J. ; Mier, J. W. ; Paietta, Elisabeth M. ; Fisher, R. I. ; Weiss, G. R. ; Doroshow, J. H. / Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine-activated killer cells. In: Journal of Clinical Oncology. 1990 ; Vol. 8, No. 7. pp. 1138-1147.
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title = "Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine-activated killer cells",
abstract = "Fifty patients with advanced melanoma received high-dose bolus and continuous infusion interleukin-2 (IL-2) with lymphokine-activated killer (LAK) cells in an attempt to improve the therapeutic index of this active but toxic therapy. Treatment began with up to nine bolus doses of IL-2 administered over 3 days. After 1 day of rest, patients underwent daily leukapheresis for 4 days, and the leukocytes were cultured with IL-2 in vitro to prepare LAK cells. Continuous infusion IL-2 was begun 1 day after the last leukapheresis and continued for up to 148 hours; LAK cells were administered on days 1, 2, and 4 of the infusion. Responding patients were eligible to receive up to two additional cycles of therapy at 3-month intervals. Most patients completed each cycle without dose reduction. One patient had complete response and six patients had partial responses (14{\%} response rate). The complete responder and three of the partial responders (8{\%}) remain free from disease progression with follow-up of 21 to 24 months. Of these four patients with durable remissions, one had extensive liver and lymph node metastases, one had lymph node, pleural, and parenchymal lung metastases, and two had disease limited to lymph nodes or subcutaneous tissues. Seventeen patients (34{\%}) required pressors for hypotension, three patients (6{\%}) developed hemodynamically significant arrhythmias, and six patients (12{\%}) developed dyspnea at rest, but none required intubation and there were no treatment-related deaths. Unacceptable toxicity developed in two patients during bolus IL-2 administration and therapy was aborted; both returned to baseline status within 4 days of discontinuing IL-2. Fever, oliguria, and elevated creatinine or transaminase levels occurred frequently but were also transient. Despite less frequent severe toxicity with this modified regimen, these results confirm the ability of IL-2 and LAK cell therapy to induce durable remissions in some patients with advanced melanoma.",
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T1 - Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine-activated killer cells

AU - Bar, M. H.

AU - Sznol, M.

AU - Atkins, M. B.

AU - Ciobanu, N.

AU - Micetich, K. C.

AU - Boldt, D. H.

AU - Margolin, K. A.

AU - Aronson, F. R.

AU - Rayner, A. A.

AU - Hawkins, M. J.

AU - Mier, J. W.

AU - Paietta, Elisabeth M.

AU - Fisher, R. I.

AU - Weiss, G. R.

AU - Doroshow, J. H.

PY - 1990

Y1 - 1990

N2 - Fifty patients with advanced melanoma received high-dose bolus and continuous infusion interleukin-2 (IL-2) with lymphokine-activated killer (LAK) cells in an attempt to improve the therapeutic index of this active but toxic therapy. Treatment began with up to nine bolus doses of IL-2 administered over 3 days. After 1 day of rest, patients underwent daily leukapheresis for 4 days, and the leukocytes were cultured with IL-2 in vitro to prepare LAK cells. Continuous infusion IL-2 was begun 1 day after the last leukapheresis and continued for up to 148 hours; LAK cells were administered on days 1, 2, and 4 of the infusion. Responding patients were eligible to receive up to two additional cycles of therapy at 3-month intervals. Most patients completed each cycle without dose reduction. One patient had complete response and six patients had partial responses (14% response rate). The complete responder and three of the partial responders (8%) remain free from disease progression with follow-up of 21 to 24 months. Of these four patients with durable remissions, one had extensive liver and lymph node metastases, one had lymph node, pleural, and parenchymal lung metastases, and two had disease limited to lymph nodes or subcutaneous tissues. Seventeen patients (34%) required pressors for hypotension, three patients (6%) developed hemodynamically significant arrhythmias, and six patients (12%) developed dyspnea at rest, but none required intubation and there were no treatment-related deaths. Unacceptable toxicity developed in two patients during bolus IL-2 administration and therapy was aborted; both returned to baseline status within 4 days of discontinuing IL-2. Fever, oliguria, and elevated creatinine or transaminase levels occurred frequently but were also transient. Despite less frequent severe toxicity with this modified regimen, these results confirm the ability of IL-2 and LAK cell therapy to induce durable remissions in some patients with advanced melanoma.

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