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Clinical Drug Investigation

, Volume 9, Issue 2, pp 79–87 | Cite as

Thymostimulin in Association with Chemotherapy in Breast Cancer Patients with Bone Metastases

  • S. Gonnelli
  • R. Petrioli
  • C. Cepollaro
  • R. Palmieri
  • A. Aquino
  • C. Gennari
Original Research Clinical Use

Summary

40 patients with predominantly osteolytic bone metastases from breast cancer, in whom first-line chemotherapy had failed, were randomly allocated to 2 groups: 20 patients received chemotherapy plus thymostimulin (CHT + Th), and 20 patients received chemotherapy alone (CHT). The occurrence of infections, response rate, bone markers and bone pain were evaluated after 3 and 6 months of treatment. The infection rate was lower in the CHT + Th group than in the CHT group (p<0.05). At the 6th month the average administered dose intensity was significantly higher in the CHT + Th group (p<0.05). Pain, as assessed by a visual analogue scale, showed a significant reduction in both groups. The hydroxyproline/creatinine ratio showed a significant reduction (p<0.05) only in CHT + Th treated patients. After 6 months of treatment, a partial response was observed in 6 of 19 evaluable patients in the CHT + Th group and in 4 of 17 evaluable patients in the CHT group. Our findings suggest that the addition of thymostimulin to chemotherapy in breast cancer patients with bone metastases reduces the infection rate and allows for the administration of the planned dose intensity.

Keywords

Breast Cancer Adis International Limited Bone Metastasis Eastern Cooperative Oncology Group Drug Invest 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Osoba D, Miller JF. Evidence for a humoral thymus factor responsible for the maturation of immunological faculty. Nature 1963; 199: 653PubMedCrossRefGoogle Scholar
  2. 2.
    Goldstein A, Low TLK, Zatz MM. Thymosins. Clin Immunol Allerg 1983; 3: 119Google Scholar
  3. 3.
    Falchetti R, Bergesi G, Eshkol A, et al. Pharmacological and biological properties of a calf thymus extract (Tp1). Drugs Exp Clin Res 1977; 3: 39–47Google Scholar
  4. 4.
    Fiorilli M, Ammirati P, Pandolfi F, et al. Immunological and clinical investigation of a bovine thymic extract. I. In vitro effect on T-cell differentiation in normal and pathological conditions. Annali Sclavo 1979; 21: 494–501PubMedGoogle Scholar
  5. 5.
    Lin CY, Chu CM. In vitro effect of a bovine extract (thymostimulin) on T-cell differentiation in cord blood lymphocytes. Pediatr Pharm 1985; 5: 181–7Google Scholar
  6. 6.
    Liberati AM, Cinieri S, Fizzotti M, et al. Modulation of NK activity by thymic hormones: in vitro effects of thymostimulin. Med Oncol Tumor Pharmacother 1989; 6: 45–52PubMedGoogle Scholar
  7. 7.
    Aiuti F, Ammirati P, Fiorilli M, et al. Immunologic and clinical investigation on a bovine thymic extract. Therapeutic applications in primary immunodeficiencies. Pediatr Res 1979; 13: 797–802PubMedCrossRefGoogle Scholar
  8. 8.
    Aiuti F, Sirianni MC, Fiorilli M, et al. A placebo-controlled trial of thymic hormone treatment of recurrent herpes simplex labialis infection in immunodeficient host: results after a 1-year follow-up. Clin Immunol Immunopathol 1984; 30: 11PubMedCrossRefGoogle Scholar
  9. 9.
    Hobbs JR. Experience in the use of Tp-1 Serono in the treatment of T-lymphocyte deficiencies. In: Hobbs JR, Byron N, editors. Thymic factor therapy. London: Academic Press, 1984Google Scholar
  10. 10.
    Shoham J, Eshel I, Aboud M, et al. Thymic hormonal activity on human peripheral blood lymphocytes, in vitro. II. Enhancement of the production of immune interferon by activated cells. J Immunol 1980; 125: 54–8PubMedGoogle Scholar
  11. 11.
    Lin CY, Low TLK. A comparative study on the immunological effects of bovine and porcine thymic extracts: induction of lymphoproliferative response and enhancement of interleukin-2, gamma interferon and tumor necrotic factor production in vitro on cord blood lymphocytes. Immunopharmacology 1989; 18: 1–10PubMedCrossRefGoogle Scholar
  12. 12.
    Klein AS, Lang R, Eshel I, et al. Modulation of immune response and tumor development in tumor bearing mice treated by the thymic factor thymostimulin. Cancer Res 1987; 47: 3351–5PubMedGoogle Scholar
  13. 13.
    Montoya JA, Martinez EM, Rodriguez M, et al. Immunochemotherapy (thymostimulin-cyclophosphamide) in dogs. Br Vet J 1990; 146: 249–54PubMedCrossRefGoogle Scholar
  14. 14.
    Villanua MA, Szary A, Esquifino AI, et al. Thymostimulin effects on lymphoid organs in Ames Dwarf mice. Acta Endocrinol 1993; 128: 74–80PubMedGoogle Scholar
  15. 15.
    Iaffaioli RW, 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 1988; 12: 69–75PubMedGoogle Scholar
  16. 16.
    Shoham J. The effect of the thymic factor thymostimulin on survival rate, immune function and resistance to infections in experimental and clinical cancer. In: Nagel G, Schioppacassi G, Schuff-Werner P, editors. Thymus hormones in oncology. Serono Symposia Review 1988; 19: 45–57Google Scholar
  17. 17.
    Farris A, Bisail M, Sarobba MG, et al. Thymostimulation in association with chemotherapy in patients with breast cancer. Terapia Moderna 1990; 4: 295–8Google Scholar
  18. 18.
    Brundt SJ, Peters WP, Atwater SK, et al. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on haemopoietic reconstitution after high-dose chemotherapy and autologous bone marrow transplantation. N Engl J Med 1988; 318: 869–76CrossRefGoogle Scholar
  19. 19.
    Dexter TM. Haemopoietic growth factors: their role in the treatment of cancer. Cancer Surv 1990; 9: 1PubMedGoogle Scholar
  20. 20.
    Neidhart JA. Dose intensive treatment of breast cancer supported by granulocyte macrophage colony-stimulating factor. Breast Cancer Res 1991; 20: 515–23Google Scholar
  21. 21.
    Neidhart JA, Mangalik A, Stidley CA, et al. Dosing regimen of granulocyte-macrophage colony-stimulating factor to support dose-intensive chemotherapy. J Clin Oncol 1992; 10: 1460–9PubMedGoogle Scholar
  22. 22.
    Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J Cancer 1987; 55: 61–6PubMedCrossRefGoogle Scholar
  23. 23.
    Sherry MM, Greco FA, Johnson DH, et al. Metastatic breast cancer confined to the skeletal system: an indolent disease. Am J Med 1986; 81: 381–6PubMedCrossRefGoogle Scholar
  24. 24.
    Gowen M, Wood DD, Ihrie EJ, et al. An interleukin-I-like factor stimulates bone resorption in vitro. Nature 1983; 306: 378–80PubMedCrossRefGoogle Scholar
  25. 25.
    Ibbotson KJ, Harrod J, Gowen M, et al. Human recombinant transforming growth factor alpha stimulates bone resorption and inhibits formation in vitro. Proc Natl Acad Sci USA 1986; 83: 2228–32PubMedCrossRefGoogle Scholar
  26. 26.
    Mundy GR. Hypercalcemia of malignancy revisited. J Clin Invest 1988; 82: 1–6PubMedCrossRefGoogle Scholar
  27. 27.
    Canalis E. Interleukin-1 has independent effects on deoxyribonucleic acid and collagen synthesis in cultures of rat calvariae. Endocrinology 1986; 118: 74–81PubMedCrossRefGoogle Scholar
  28. 28.
    Canalis E. Effects of tumor necrosis factor on bone formation in vitro. Endocrinology 1987; 121: 1596–604PubMedCrossRefGoogle Scholar
  29. 29.
    Modrowsky D, Hott M, Buret B, et al. Gn-CSF is an autocrine mitogenic factor for normal human osteoblastic cells isolated from the trabecular bone surface. Bone Miner 1992; 17(Suppl. 1): 69SGoogle Scholar
  30. 30.
    Prockop DJ, Udenfriend S. A specific method for the analysis of hydroxyproline in tissues and urine. Anal Biochem 1969; 1: 228–39CrossRefGoogle Scholar
  31. 31.
    Francini G, Gonnelli S, Petrioli R, et al. Treatment of bone metastases with dichloromethylene bisphosphonate. J Clin Oncol 1993; 10: 591–6Google Scholar
  32. 32.
    Scott J, Huskisson EC. Graphic representation of pain. Pain 1976; 175–84Google Scholar
  33. 33.
    Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: 649–55PubMedCrossRefGoogle Scholar
  34. 34.
    Hayward JL, Carbone PP, Heuson JC, et al. Assessment of response to therapy in advanced breast cancer. Cancer 1977; 39: 1289PubMedCrossRefGoogle Scholar
  35. 35.
    Kaplan EL, Meier P. Non parametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–81CrossRefGoogle Scholar
  36. 36.
    Peto R, Pike MC, Armitage P. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. Br J Cancer 1977; 35: 1–39PubMedCrossRefGoogle Scholar
  37. 37.
    Scheid V, Buzdar AU, Smith TL, et al. Clinical course of breast cancer patients with osseous metastasis treated with combination chemotherapy. Cancer 1986; 58: 2589–93PubMedCrossRefGoogle Scholar
  38. 38.
    Francini G, Petrioli R, Aquino A, et al. Advanced breast cancer treatment with folinic acid, 5-fluorouracil, and mitomycin C. Cancer Chemother Pharmacol 1993; 32: 359–64PubMedCrossRefGoogle Scholar
  39. 39.
    Dodwell DJ, Howell A. The systemic treatment of bone metastases. In: Rubens RD, Fogelman I, editors. Bone metastases: diagnosis and treatment. New York: Springer-Verlag 1991: 121–48Google Scholar
  40. 40.
    Henderson IC. Chemotherapy for advanced disease. In: Harris JR, Henderson IC, Kinne DV, editors. Breast disease. Philadelphia: JB Lippincott 1987: 428–58Google Scholar
  41. 41.
    Coleman RE, Whitaker KD, Moss DW. Biochemical monitoring predicts response in bone metastases to treatment. Br J Cancer 1988; 58: 205–10PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • S. Gonnelli
    • 1
  • R. Petrioli
    • 2
  • C. Cepollaro
    • 1
  • R. Palmieri
    • 1
  • A. Aquino
    • 2
  • C. Gennari
    • 1
  1. 1.Institute of Internal MedicineUniversity of SienaSienaItaly
  2. 2.Division of Medical OncologyUniversity of SienaSienaItaly

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