Advertisement

Investigational New Drugs

, Volume 22, Issue 1, pp 75–81 | Cite as

Phase II Study of Interferon Gamma in Malignant Carcinoid Tumors (E9292): A Trial of the Eastern Cooperative Oncology Group

  • Keith Stuart
  • Donna E. Levy
  • Tom Anderson
  • Constantine A. Axiotis
  • Janice P. Dutcher
  • Andrew Eisenberg
  • John K. Erban
  • Al Bowen BensonIII
Article

Abstract

Purpose: To determine the safety and efficacy of treatment with gamma interferon (IFNγ) in patients with metastatic carcinoid tumor. Patients and methods: 51 patients were enrolled on this Phase II Eastern Cooperative Oncology Group (ECOG) study. Seventy five percent of them had hormonally active tumors. Treatment consisted of IFNγ subcutaneously at a daily dose of 0.1 mg/m2. Patents were evaluated for toxicity weekly for the first month and monthly thereafter; response was determined radiologically every 8 weeks. Results: Patients received treatment with IFNγ for a median of 17.9 weeks (range 2–175). Toxicity was generally mild and expected: 61% experienced noninfected fever and 21% developed granulocytopenia. Three patients (6%) had a partial response; there were no complete responses. Median time to progression was 5.5 months (95% confidence interval 3.9–11.1). The 1-year progression free rate was 28% (13.4–43.4%). Median survival was 42 months, with a 1-year survival rate of 67% (53.3–80%). Discussion: This Phase II study demonstrated that therapy with IFNγ in patients with metastatic carcinoid tumor was well-tolerated, but did not produce significant antitumor effects. The overall results were somewhat comparable to those previously seen with alpha interferons as well as cytotoxic drugs.

carcinoid interferon 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Modlin IM, Sandor A: An analysis of 8305 cases of carcinoid tumors. Cancer 79(4): 813–829, 1997Google Scholar
  2. 2.
    Creutzfeldt W, Stockmann F: Carcinoids and carcinoid syndrome. Am J Med 82(5B): 4–16, 1987Google Scholar
  3. 3.
    Kulke MH, Mayer RJ: Carcinoid tumors. N Engl J Med 340(11): 858–868, 1999Google Scholar
  4. 4.
    Moertel CG: Kamofsky memorial lecture. An odyssey in the land of small tumors. J Clin Oncol 5(10): 1502–1522Google Scholar
  5. 5.
    Creutzfeldt W: Historical background and natural history of carcinoids. Digestion 55(3): 3–10, 1994Google Scholar
  6. 6.
    Perry LJ et al.: Hepatic arterial chemoembolization for metastatic neuroendocrine tumors. Surgery 116(6): 1111–1116; discussion 1116–1117, 1994Google Scholar
  7. 7.
    Oberg K et al.: Treatment of malignant carcinoid tumors with human leukocyte interferon: Long-term results. Cancer Treat Rep 70(11): 1297–1304, 1986Google Scholar
  8. 8.
    Carlin JM et al.: Biologic-response-modifier-induced indoleamine 2,3-dioxygenase activity in human peripheral blood mononuclear cell cultures. J Immunol 139(7): 2414–2418, 1987Google Scholar
  9. 9.
    Markman M: Models for the antitumor action of interferon against human ovarian cancer. Annual Meeting of the International Society for Interferon Research, 1991Google Scholar
  10. 10.
    Ozaki Y, Edelstein MP, Duch DS: Induction of indoleamine 2,3-dioxygenase: A mechanism of the antitumor activity of interferon gamma. Proc Natl Acad Sci USA 85(4): 1242–1246, 1988Google Scholar
  11. 11.
    de la Maza LM, Peterson EM: Dependence of the in vitro antiproliferative activity of recombinant human gamma-interferon on the concentration of tryptophan in culture media. Cancer Res 48(2): 346–350, 1988Google Scholar
  12. 12.
    Takikawa O et al.: Mechanism of interferon-gamma action. Characterization of indoleamine 2,3-dioxygenase in cultured human cells induced by interferon-gamma and evaluation of the enzyme-mediated tryptophan degradation in its anticellular activity. J Biol Chem 263(4): 2041–2048, 1988Google Scholar
  13. 13.
    WHO Handbook for Reporting Results of Cancer Treatment. Geneva (Switzerland): World Health Organization Offset Publication No. 48; 1979Google Scholar
  14. 14.
    Kaplan EL: Nonparametric estimation of incomplete observations. J Amer Statist Assoc 53: 457–481, 1958Google Scholar
  15. 15.
    Oberg K, Eriksson B: The role of interferons in the management of carcinoid tumours. Br J Haematol 79(1): 74–77, 1991Google Scholar
  16. 16.
    Oberg K: Carcinoid tumors: Current Concepts in Diagnosis and Treatment. Oncologist 3(5): 339–345, 1998Google Scholar
  17. 17.
    Dirix LY et al.: Long-term results of continuous treatment with recombinant interferon-alpha in patients with metastatic carcinoid tumors -an antiangiogenic effect? Anti-Cancer Drugs 7(2): 175–181, 1996Google Scholar
  18. 18.
    Di Bartolomeo M et al.: Treatment of carcinoid syndrome with recombinant interferon alpha-2a. Acta Oncol 32(2): 235–238, 1993Google Scholar
  19. 19.
    Joensuu H, Kumpulainen E, Grohn P: Treatment of metastatic carcinoid tumour with recombinant interferon alfa. Eur J Cancer 28A(10): 1650–1653Google Scholar
  20. 20.
    Valimaki M et al.: Is the treatment of metastatic carcinoid tumor with interferon not as successful as suggested? Cancer. 67(3): 547–549, 1991Google Scholar
  21. 21.
    Janson ET, Kauppinen HL, Oberg K: Combined alpha-and gamma-interferon therapy for malignant midgut carcinoid tumors. A phase I–II trial. Acta Oncol 32(2): 231–233, 1993Google Scholar
  22. 22.
    di Bartolomeo M, et al.: Clinical efficacy of octreotide in the treatment of metastatic neuroendocrine tumors. A study by the Italian Trials in Medical Oncology Group. Cancer 77(2): 402–8, 1996Google Scholar
  23. 23.
    Joensuu H, Katka K, Kujari H: Dramatic response of a metastatic carcinoid tumour to a combination of interferon and octreotide. Acta Endocrinol (Copenh) 126(2): 184–185, 1992Google Scholar
  24. 24.
    Janson ET, Oberg K: Long-term management of the carcinoid syndrome. Treatment with octreotide alone and in combination with alpha-interferon. Acta Oncol 32(2): 225–229, 1993Google Scholar
  25. 25.
    van Hazel GA, Rubin J, Moertel CG: Treatment of metastatic carcinoid tumor with dactinomycin or dacarbazine. Cancer Treat Rep 67(6): 583–585, 1983Google Scholar
  26. 26.
    Engstrom PF et al.: Streptozocin plus fluorouracil versus doxorubicin therapy for metastatic carcinoid tumor. J Clin Oncol 2(11): 1255–1259, 1984Google Scholar
  27. 27.
    Feldman JM et al.: Streptozotocin treatment of metastatic carcinoid tumors. South Med J 65(11): 1325–1327, 1972Google Scholar
  28. 28.
    Iweze FI, Owen-Smith M, Polak J: Carcinoid syndrome treated with streptozotocin. Proc R Soc Med 65(2): 164–165, 1972Google Scholar
  29. 29.
    Moertel CG: Treatment of the carcinoid tumor and the malignant carcinoid syndrome. J Clin Oncol 1(11): 727–740, 1983Google Scholar
  30. 30.
    Moertel CG, Rubin J, O'Connell MJ: Phase II study of cisplatin therapy in patients with metastatic carcinoid tumor and the malignant carcinoid syndrome. Cancer Treat Rep 70(12): 1459–1460, 1986Google Scholar
  31. 31.
    Bukowski RM et al.: Phase II trial of dimethyltriazenoimidazole carboxamide in patients with metastatic carcinoid. A Southwest Oncology Group study. Cancer 73(5): 1505–1508, 1994Google Scholar
  32. 32.
    Bukowski RM et al.: A phase II trial of combination chemotherapy in patients with metastatic carcinoid tumors. A Southwest Oncology Group Study. Cancer 60(12): 2891–2895, 1987Google Scholar
  33. 33.
    Chernicoff D et al.: Combination chemotherapy for islet cell carcinoma and metastatic carcinoid tumors with 5-fluorouracil and streptozotocin. Cancer Treat Rep 63(5): 795–796, 1979Google Scholar
  34. 34.
    Moertel CG, Hanley JA: Combination chemotherapy trials in metastatic carcinoid tumor and the malignant carcinoid syndrome. Cancer Clin Trials 2(4): 327–334, 1979Google Scholar
  35. 35.
    Ridolfi R et al.: Chemotherapy with 5-fluorouracil and streptozotocin in carcinoid tumors of gastrointestinal origin: Experiences with 13 patients. J Chemother 3(5): 328–331, 1991Google Scholar
  36. 36.
    Andreyev HJ et al.: Phase II study of continuous infusion fluorouracil and interferon alfa-2b in the palliation of malignant neuroendocrine tumors. J Clin Oncol 13(6): 1486–1492, 1995Google Scholar
  37. 37.
    Quaedvlieg PF et al.: Epidemiology and survival in patients with carcinoid disease in The Netherlands. An epidemiological study with 2391 patients. Ann Oncol 12(9): 1295–1300, 2001Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Keith Stuart
    • 1
  • Donna E. Levy
    • 2
  • Tom Anderson
    • 3
  • Constantine A. Axiotis
    • 4
  • Janice P. Dutcher
    • 5
  • Andrew Eisenberg
    • 6
  • John K. Erban
    • 7
  • Al Bowen BensonIII
    • 8
  1. 1.Beth Israel Deaconess Medical CenterBoston
  2. 2.Dana Farber Cancer InstituteBoston
  3. 3.Billings Oncology AssociatesBillings
  4. 4.SUNY Health Science Center at BrooklynBrooklyn
  5. 5.Our Lady of Mercy Medical Center MBCCOPBronx
  6. 6.St Joseph Mercy HospitalAnn Arbor
  7. 7.New England Medical CenterBoston
  8. 8.Northwestern UniversityChicago

Personalised recommendations