Dose-related immunologic effects of levamisole in patients with cancer

John Edward Janik, W. C. Kopp, J. W. Smith, D. L. Longo, W. G. Alvord, W. H. Sharfman, R. G. Fenton, M. Sznol, R. G. Steis, S. P. Creekmore, C. H. Ewel, J. Hursey, W. J. Urba

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Purpose: This phase I study was conducted to determine the maximum- tolerated dose (MTD) and the immunologic properties of levamisole in cancer patients when administered alone and in combination with interferon gamma (IFN-γ). Patients and Methods: Twenty patients with advanced cancer and 36 patients with completely resected melanoma (n = 33) or renal cell cancer (n = 3) received levamisole orally every other day for six doses at 1.0, 2.5, 5.0, or 10.0 mg/kg. Ten days later, patients restarted levamisole and began IFN- γ 0.1 mg/m2 by subcutaneous injection every other day. Blood samples were collected for measurement of neopterin and soluble interleukin-2 receptor (sIL-2R), and for flow-cytometric analysis. Results: The MTD of levamisole was 5 mg/kg, and this was not changed by the addition of IFN-γ. Dose- related increases in serum levels of neopterin and sIL-2R were noted. Multiple doses of ≥ 5 mg/kg of levamisole were required to elicit immune changes, which were more prominent in patients with minimal tumor burdens. Increased expression of CD64 and class I and class II major histocompatibility antigens on monocytes was also observed. The combination of IFN-γ and levamisole did not result in greater immunologic effects than those observed in previous trials of IFN-γ alone. Conclusion: Levamisole induces dose-related immunologic changes in patients with large or minimal tumor burdens. These changes may be involved in the beneficial effects noted in recent adjuvant trials of levamisole. Ongoing clinical trials should correlate immune changes with response, and trials exploring different schedules of administration using higher, more immunologically active, doses of levamisole should be performed.

Original languageEnglish (US)
Pages (from-to)125-135
Number of pages11
JournalJournal of Clinical Oncology
Volume11
Issue number1
DOIs
StatePublished - Jan 1 1993

Fingerprint

Levamisole
Interferon-gamma
Neoplasms
Neopterin
Maximum Tolerated Dose
Interleukin-2 Receptors
Tumor Burden
Histocompatibility Antigens Class II
Subcutaneous Injections
Renal Cell Carcinoma
Monocytes
Melanoma
Appointments and Schedules
Clinical Trials

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Janik, J. E., Kopp, W. C., Smith, J. W., Longo, D. L., Alvord, W. G., Sharfman, W. H., ... Urba, W. J. (1993). Dose-related immunologic effects of levamisole in patients with cancer. Journal of Clinical Oncology, 11(1), 125-135. https://doi.org/10.1200/JCO.1993.11.1.125

Dose-related immunologic effects of levamisole in patients with cancer. / Janik, John Edward; Kopp, W. C.; Smith, J. W.; Longo, D. L.; Alvord, W. G.; Sharfman, W. H.; Fenton, R. G.; Sznol, M.; Steis, R. G.; Creekmore, S. P.; Ewel, C. H.; Hursey, J.; Urba, W. J.

In: Journal of Clinical Oncology, Vol. 11, No. 1, 01.01.1993, p. 125-135.

Research output: Contribution to journalArticle

Janik, JE, Kopp, WC, Smith, JW, Longo, DL, Alvord, WG, Sharfman, WH, Fenton, RG, Sznol, M, Steis, RG, Creekmore, SP, Ewel, CH, Hursey, J & Urba, WJ 1993, 'Dose-related immunologic effects of levamisole in patients with cancer', Journal of Clinical Oncology, vol. 11, no. 1, pp. 125-135. https://doi.org/10.1200/JCO.1993.11.1.125
Janik JE, Kopp WC, Smith JW, Longo DL, Alvord WG, Sharfman WH et al. Dose-related immunologic effects of levamisole in patients with cancer. Journal of Clinical Oncology. 1993 Jan 1;11(1):125-135. https://doi.org/10.1200/JCO.1993.11.1.125
Janik, John Edward ; Kopp, W. C. ; Smith, J. W. ; Longo, D. L. ; Alvord, W. G. ; Sharfman, W. H. ; Fenton, R. G. ; Sznol, M. ; Steis, R. G. ; Creekmore, S. P. ; Ewel, C. H. ; Hursey, J. ; Urba, W. J. / Dose-related immunologic effects of levamisole in patients with cancer. In: Journal of Clinical Oncology. 1993 ; Vol. 11, No. 1. pp. 125-135.
@article{823195c42316402187df2bdc80a13fb5,
title = "Dose-related immunologic effects of levamisole in patients with cancer",
abstract = "Purpose: This phase I study was conducted to determine the maximum- tolerated dose (MTD) and the immunologic properties of levamisole in cancer patients when administered alone and in combination with interferon gamma (IFN-γ). Patients and Methods: Twenty patients with advanced cancer and 36 patients with completely resected melanoma (n = 33) or renal cell cancer (n = 3) received levamisole orally every other day for six doses at 1.0, 2.5, 5.0, or 10.0 mg/kg. Ten days later, patients restarted levamisole and began IFN- γ 0.1 mg/m2 by subcutaneous injection every other day. Blood samples were collected for measurement of neopterin and soluble interleukin-2 receptor (sIL-2R), and for flow-cytometric analysis. Results: The MTD of levamisole was 5 mg/kg, and this was not changed by the addition of IFN-γ. Dose- related increases in serum levels of neopterin and sIL-2R were noted. Multiple doses of ≥ 5 mg/kg of levamisole were required to elicit immune changes, which were more prominent in patients with minimal tumor burdens. Increased expression of CD64 and class I and class II major histocompatibility antigens on monocytes was also observed. The combination of IFN-γ and levamisole did not result in greater immunologic effects than those observed in previous trials of IFN-γ alone. Conclusion: Levamisole induces dose-related immunologic changes in patients with large or minimal tumor burdens. These changes may be involved in the beneficial effects noted in recent adjuvant trials of levamisole. Ongoing clinical trials should correlate immune changes with response, and trials exploring different schedules of administration using higher, more immunologically active, doses of levamisole should be performed.",
author = "Janik, {John Edward} and Kopp, {W. C.} and Smith, {J. W.} and Longo, {D. L.} and Alvord, {W. G.} and Sharfman, {W. H.} and Fenton, {R. G.} and M. Sznol and Steis, {R. G.} and Creekmore, {S. P.} and Ewel, {C. H.} and J. Hursey and Urba, {W. J.}",
year = "1993",
month = "1",
day = "1",
doi = "10.1200/JCO.1993.11.1.125",
language = "English (US)",
volume = "11",
pages = "125--135",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "1",

}

TY - JOUR

T1 - Dose-related immunologic effects of levamisole in patients with cancer

AU - Janik, John Edward

AU - Kopp, W. C.

AU - Smith, J. W.

AU - Longo, D. L.

AU - Alvord, W. G.

AU - Sharfman, W. H.

AU - Fenton, R. G.

AU - Sznol, M.

AU - Steis, R. G.

AU - Creekmore, S. P.

AU - Ewel, C. H.

AU - Hursey, J.

AU - Urba, W. J.

PY - 1993/1/1

Y1 - 1993/1/1

N2 - Purpose: This phase I study was conducted to determine the maximum- tolerated dose (MTD) and the immunologic properties of levamisole in cancer patients when administered alone and in combination with interferon gamma (IFN-γ). Patients and Methods: Twenty patients with advanced cancer and 36 patients with completely resected melanoma (n = 33) or renal cell cancer (n = 3) received levamisole orally every other day for six doses at 1.0, 2.5, 5.0, or 10.0 mg/kg. Ten days later, patients restarted levamisole and began IFN- γ 0.1 mg/m2 by subcutaneous injection every other day. Blood samples were collected for measurement of neopterin and soluble interleukin-2 receptor (sIL-2R), and for flow-cytometric analysis. Results: The MTD of levamisole was 5 mg/kg, and this was not changed by the addition of IFN-γ. Dose- related increases in serum levels of neopterin and sIL-2R were noted. Multiple doses of ≥ 5 mg/kg of levamisole were required to elicit immune changes, which were more prominent in patients with minimal tumor burdens. Increased expression of CD64 and class I and class II major histocompatibility antigens on monocytes was also observed. The combination of IFN-γ and levamisole did not result in greater immunologic effects than those observed in previous trials of IFN-γ alone. Conclusion: Levamisole induces dose-related immunologic changes in patients with large or minimal tumor burdens. These changes may be involved in the beneficial effects noted in recent adjuvant trials of levamisole. Ongoing clinical trials should correlate immune changes with response, and trials exploring different schedules of administration using higher, more immunologically active, doses of levamisole should be performed.

AB - Purpose: This phase I study was conducted to determine the maximum- tolerated dose (MTD) and the immunologic properties of levamisole in cancer patients when administered alone and in combination with interferon gamma (IFN-γ). Patients and Methods: Twenty patients with advanced cancer and 36 patients with completely resected melanoma (n = 33) or renal cell cancer (n = 3) received levamisole orally every other day for six doses at 1.0, 2.5, 5.0, or 10.0 mg/kg. Ten days later, patients restarted levamisole and began IFN- γ 0.1 mg/m2 by subcutaneous injection every other day. Blood samples were collected for measurement of neopterin and soluble interleukin-2 receptor (sIL-2R), and for flow-cytometric analysis. Results: The MTD of levamisole was 5 mg/kg, and this was not changed by the addition of IFN-γ. Dose- related increases in serum levels of neopterin and sIL-2R were noted. Multiple doses of ≥ 5 mg/kg of levamisole were required to elicit immune changes, which were more prominent in patients with minimal tumor burdens. Increased expression of CD64 and class I and class II major histocompatibility antigens on monocytes was also observed. The combination of IFN-γ and levamisole did not result in greater immunologic effects than those observed in previous trials of IFN-γ alone. Conclusion: Levamisole induces dose-related immunologic changes in patients with large or minimal tumor burdens. These changes may be involved in the beneficial effects noted in recent adjuvant trials of levamisole. Ongoing clinical trials should correlate immune changes with response, and trials exploring different schedules of administration using higher, more immunologically active, doses of levamisole should be performed.

UR - http://www.scopus.com/inward/record.url?scp=0027394684&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027394684&partnerID=8YFLogxK

U2 - 10.1200/JCO.1993.11.1.125

DO - 10.1200/JCO.1993.11.1.125

M3 - Article

C2 - 8418223

AN - SCOPUS:0027394684

VL - 11

SP - 125

EP - 135

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 1

ER -