TY - JOUR
T1 - Pilot study of interleukin-2 and lymphokine-activated killer cells combined with immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a in patients with metastatic melanoma and renal cell carcinoma
AU - Sznol, Mario
AU - Clark, Jeffrey W.
AU - Smith, John W.
AU - Steis, Ronald G.
AU - Urba, Walter J.
AU - Rubinstein, Lawrence V.
AU - Vandermolen, Louis A.
AU - Janik, John Edward
AU - Sharfman, William H.
AU - Fenton, Robert G.
AU - Creekmore, Stephen P.
AU - Kremers, Peter
AU - Conlon, Kevin
AU - Hersey, Jean
AU - Beveridge, Joy
AU - Longo, Dan L.
N1 - Funding Information:
Received November 21, 1991; revised February 21, 1992; accepted March 3, 1992. Supported in part by Public Health Service contract NOI-CO-74102 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. M. Sznol, Clinical Research Branch, Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute (NCI), NCI-Frederick Cancer Research and Development Center, Frederick, Md.; and Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment, NCI, Bethesda, Md. J. W. Clark, J. W. Smith II, R. G. Steis, L. A. VanderMolen, J. Janik, W. H. Sharfman, R. G. Fenton, S. P. Creekmore, K. Conlon, D. L. Longo, Clinical Research Branch, Biological Response Modifiers Program, Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center. W. J. Urba, J. Beveridge, Program Resources Inc./DynCorp, NCI-Frederick Cancer Research and Development Center. L. V. Rubinstein, Biometric Research Branch, Cancer Therapy EvaJuation Program, Division of Cancer Treatment, NCI, Bethesda. P. Kremers, J. Hersey, Frederick Memorial Hospital. We thank the Biological Response Modifiers Program nursing staff for providing excellent care to the patients and Terry Phillips for her outstanding work as editorial assistant. Correspondence to: Mario Sznol, M.D., Executive Plaza North, Rm. 715, National Institutes of Health, Bethesda, MD 20892.
PY - 1992/6/17
Y1 - 1992/6/17
N2 - Background: Experiments in animal tumor models suggest that the antitumor effects of interleukin-2 (IL-2) or IL-2 in combination with lymphokine-activated killer (LAK) cells can be enhanced by chemotherapy agents such as cyclo-phosphamide or doxorubicin or by the biologic agent interferon α. Purpose: We determined the toxicity and clinical response rate of an IL-2-LAK cell regimen modified by the addition of moderate, immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a (IFN α-2a) in patients with metastatic melanoma and renal cell carcinoma. Methods: IL-2(3-6 million units/m2 per day) was administered by continuous infusion on days 0-5 and days 11-16. LAK cells were infused on days 11 and 12 or on days 11, 12, and 14. Low doses of cyclophosphamide (300 mg/ m2) and doxorubicin (25 mg/m2) were given on day 9 before the LAK cell infusions. Following the IL-2-LAK cell infusion, IFN α-2a (12 million units/m2) was administered for a total of nine doses to complete a cycle of treatment. A total of 89 patients were enrolled in the study. Results: For each histology, there were eight partial responses in 40 assessable patients, for an overall response rate of 20% (90% confidence interval = 10%-33%). The median response duration was 5 months, although two patients with renal cell carcinoma and one patient with metastatic melanoma had almost complete disappearance of tumor and are still responding after 26+, 22+, and 26+ months, respectively. Toxic effects were severe in patients receiving the highest dose of IL-2 administered in this study and similar to those reported with other high-dose IL-2-LAK cell regimens. Although toxic effects were completely reversible in most patients, there were four treatment-related deaths. Conclusions: This regimen is active in patients with metastatic melanoma and renal cell carcinoma and produces meaningful responses in a small percentage of these patients; however, it is not clear whether cyclophosphamide, doxorubicin, and IFN a-2α as used in this protocol appreciably augmented the antitumor activity of the IL-2-LAK cell regimen.
AB - Background: Experiments in animal tumor models suggest that the antitumor effects of interleukin-2 (IL-2) or IL-2 in combination with lymphokine-activated killer (LAK) cells can be enhanced by chemotherapy agents such as cyclo-phosphamide or doxorubicin or by the biologic agent interferon α. Purpose: We determined the toxicity and clinical response rate of an IL-2-LAK cell regimen modified by the addition of moderate, immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a (IFN α-2a) in patients with metastatic melanoma and renal cell carcinoma. Methods: IL-2(3-6 million units/m2 per day) was administered by continuous infusion on days 0-5 and days 11-16. LAK cells were infused on days 11 and 12 or on days 11, 12, and 14. Low doses of cyclophosphamide (300 mg/ m2) and doxorubicin (25 mg/m2) were given on day 9 before the LAK cell infusions. Following the IL-2-LAK cell infusion, IFN α-2a (12 million units/m2) was administered for a total of nine doses to complete a cycle of treatment. A total of 89 patients were enrolled in the study. Results: For each histology, there were eight partial responses in 40 assessable patients, for an overall response rate of 20% (90% confidence interval = 10%-33%). The median response duration was 5 months, although two patients with renal cell carcinoma and one patient with metastatic melanoma had almost complete disappearance of tumor and are still responding after 26+, 22+, and 26+ months, respectively. Toxic effects were severe in patients receiving the highest dose of IL-2 administered in this study and similar to those reported with other high-dose IL-2-LAK cell regimens. Although toxic effects were completely reversible in most patients, there were four treatment-related deaths. Conclusions: This regimen is active in patients with metastatic melanoma and renal cell carcinoma and produces meaningful responses in a small percentage of these patients; however, it is not clear whether cyclophosphamide, doxorubicin, and IFN a-2α as used in this protocol appreciably augmented the antitumor activity of the IL-2-LAK cell regimen.
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U2 - 10.1093/jnci/84.12.929
DO - 10.1093/jnci/84.12.929
M3 - Article
C2 - 1629914
AN - SCOPUS:0026638797
SN - 0027-8874
VL - 84
SP - 929
EP - 937
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 12
ER -
