Summary
We investigated the effects of thymostimulin (TST) vs placebo administration in a randomised trial performed in patients with locally advanced non-small-cell lung cancer treated with a combined modality programme that included hyperfractionated split-course thoracic radiation therapy plus chemotherapy.
Grade 3 to 4 neutropenia, severe anaemia, treatment delays due to myelosuppression, and overall infectious event rate were all less frequent in TST-treated patients, but none of these differences reached statistical significance. However, the fungine infection rate was significantly lower in the TST group, and natural killer (NK) cell activity was significantly increased in TST-treated patients.
TST is believed to work mainly as a complex immunomodulator, which acts through stimulation of T cell maturation, T cell-mediated cytotoxicity, lymphokine production by T cells, regulation of lymphoid cell functions, modulation of NK cell activity and, possibly, restoration of depressed monocyte and dendritic cell function. Our study confirms that TST is capable of improving the tolerance to antitumour treatment, and thus improving the outcome of therapy.
Similar content being viewed by others
References
Aiuti F, Fiorilli M, Schirrmacher V. Effect of thymus factor on human precursor T lymphocytes. Clinical and Experimental Immunology 20: 499, 1975
Alba E, Visentin L, Farina C. Prevention of infection and improvement of cenesthesia with thymostimulin during chemotherapy following mastectomy. Minerva Ginecologica 43: 585, 1991
Balleari E, Timitilli S, Musselli C, et al. In vivo hemopoietic activity of thymic extract ‘thymostumulin’ in aged healthy humans. Thymus 19: 59, 1992
Bernengo MG, Fra P, Lisa F, et al. Thymostimulin therapy in melanoma patients. Correlation of immunological effects with clinical course. Clinical Immunology and Immunopathology 28: 311, 1983
Braakman E, Van de Winkel JG, Van Krimpen BA, et al. CD 16 on human gamma delta T lymphocytes: expression, function, and specificity for mouse IgG isotypes. Cell Immunology 143: 97, 1992
Falchetti R, Bergesi G, Eshkol A. Pharmacological and biological properties of a calf thymus extract. Drug Experimental and Clinical Research 3: 39, 1977
Hanna N. In vivo activities of NK cells against primary and meta-static tumors in experimental animals. In Lotzova et al. (Eds) Immunobiology of natural killer cells, CRC Press, Boca Raton, Florida, USA, 1986 Herberman RB. (Ed.) NK and other natural effector cells. Academic Press, New York, 1982
Iaffaioli RV, Frasci G, Tortora G, et al. Effect of thymic extract ‘thymostimulin’ on the incidence of infections and myelotoxicity during adjuvant chemotherapy for breast cancer. Thymus 12: 69, 1988
Jacobs R, Stoll M, Stratmann G, et al. CD 16-CD56+ natural killer cells after bone marrow transplantation. Blood 79: 3239, 1992
Molto’ LM, Carballido JA, Manzano L. Thymostimulin enhances the natural cytotoxic activity of patients with transitional cell carcinoma of the bladder. International Journal of Immunopharmacology 15: 335, 1993
Pistoia V, Ghio R, Roncella S, et al. Production of colony stimulating activity by normal and neoplastic human B lymphocytes. Blood 69: 1340, 1987
Schulof RS. Thymic peptide hormones: basic properties and clinical applications in cancer. CRC Critical Reviews in Oncology and Hematology 3: 309, 1985
Schulof RS, Lloyd MS, Cleary PA, et al. A randomized trial to evaluate the immunorestorative properties of synthetic thymosin alpha 1 in patients with lung cancer. Journal of Biological Response Modifiers 4: 147, 1985
Serrate SA, Schulof RS, Leondaridis L, et al. Modulation of human natural killer cytotoxic activity, lymphokine production, and inter-leukin 2 receptor expression by thymic hormones. Journal of Immunology 139: 2338, 1987
Sztein MB. Mechanisms of action of thymic hormones. In Kouttab (Ed.) Thymic hormones: immunologic mechanisms and therapeutic action, Churchill Livingstone, New York, USA, 1987
Sztein MB, Goldstein AL. Thymic hormones: a clinical update. Springer Seminars in Immunopathology 9: 1, 1986
Sztein MB, Serrate SA, Goldstein AL. Modulation of interleukin 2 receptor expression on normal human lymphocytes by thymic hormones. Proceedings of the National Academy of Sciences of the United States of America 83: 6107, 1986
Tas MPR, Simons PJ, Balm FJM, et al. Depressed monocyte polarisation and clustering of dendritic cells in patients with head and neck cancer: in vitro restoration of this immunosuppression by thymic hormones. Cancer Immunology and Immunotherapy 36: 108, 1993
Zatz MM, Oliver J, Samuels C, et al. Thymosin increases production of T-cell growth factor by normal peripheral blood lymphocytes. Proceedings of the National Academy of Sciences of the United States of America 81: 2882, 1984
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Iaffaioli, R.V., Caponigro, F., Facchini, G. et al. Immunological and Clinical Effects of Thymostimulin in Patients with Locally Advanced Non-Small-Cell Lung Cancer Treated with Combined Chemoradiotherapy. Drug Invest 7, 209–214 (1994). https://doi.org/10.1007/BF03257412
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03257412