Advertisement

Investigational New Drugs

, Volume 6, Issue 2, pp 105–113 | Cite as

Mitoxantrone in combination with prednimustine in treatment of unfavorable non-Hodgkin lymphoma

  • Karl E. Landys
Clinical Studies

Summary

Mitoxantrone (Novantrone®) and prednimustine (Sterecyt®) are both active as single agents in the treatment of unfavorable non-Hodgkin lymphoma (UNHL). The efficacy and toxicity of the combination of these agents (NOSTE) was evaluated in 28 patients with advanced histopathologically proven UNHL who were not eligible for aggressive conventional chemotherapy. The median age was 68, range 45–84. Sixteen patients were previously untreated. Eleven patients had received doxorubicin or epidoxorubicin containing regimens and 1 patient had received CVP as first line therapy. MUGA scan was used in monitoring cardiac function in patients with cardiac risk. Novantrone® was administered at a dose of 8 mg/m2 IV on days 1 and 2 and Sterecyt® as an absolute dose 100 mg/≤ 1.6 m2–150 mg/> 1.6 m2 on days 1 through 5. The regimen was repeated every 4th week. The number of courses per patient ranged from 2 to 10. Objective response was obtained in 22 (78%) patients (20 CR and 2 PR). No response occurred in 6 patients (4 SD, 2 PD). Decreased left ventricular ejection fraction was recorded in 1 patient who suffered from asthma and ischemic heart disease. Hematological toxicity was tolerable. Gastrointestinal toxicity was rare. No hair loss was observed. After a median follow-up of 28 months the crude survival was 46%. Twelve of twenty complete responders are still in remission, the median duration of remission is 28.3 months, range 15–37.

NOSTE in this pilot study showed a high response rate, good tolerance and mild toxicity. NOSTE reduced the discomfort associated with conventional dose anthracycline-containing regimens and could be safely used in the treatment of elderly patients.

Key words

mitoxantrone prednimustine unfavorable non-Hodgkin lymhoma combination chemotherapy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison ES, Butler JJ, Byrne GE, Moon TE, Fisher R, Haskins CL, Coltman CA: Superiority of Adriamycin containing combination chemotherapy in the treatment of diffuse lymphoma. Cancer 43:417–425, 1979Google Scholar
  2. 2.
    Armitage JO, Fyfe MAE, Lewis J: Long-term remission durability and functional status of patients treated for diffuse histiocytic lymphoma with the CHOP regimen. J Clin Oncol 2:898–902, 1984Google Scholar
  3. 3.
    Sweet DL, Golomb HM, Ultmann JE, Miller JB, Stein RS, Lester EP, Mintz U, Bitran JD, Streuli RA, Daly K, Roth NO: Cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) combination sequential chemotherapy for advanced diffuse histiocytic lymphoma. Ann Intern Med 92:785–790, 1980Google Scholar
  4. 4.
    Todd M, Cadman E, Spiro P, Bertino J, Farber L, Waldron J, Fisher D: A follow-up of a randomized study comparing two chemotherapy treatments for advanced histiocytic lymphoma. J Clin Oncol 2:986–998, 1984Google Scholar
  5. 5.
    Skarin AT, Canellos GP, Rosenthal DS, Maloney WC, Frei E III: Improved prognosis of diffuse histiocytic and undifferentiated lymphoma by use of high dose methotrexate alternating with standard agents (M-BACOD). J Clin Oncol 1:91–97, 1983Google Scholar
  6. 6.
    Laurence J, Colemn M, Allen SL, Silver RT, Pasmantier M: Combination chemotherapy of advanced diffuse histiocytic lymphoma with the sic drug COP-BLAM regimen. Ann Intern Med 97:190–195, 1982Google Scholar
  7. 7.
    Fisher RI, De Vita VT, Hubbard SM, Longo DL, Wesley R, Chabner BA, Young RC: Diffuse Aggressive Lymphomas; Increased Survival After Alternating Flexible Sequences of ProMACE and MOPP Chemotherapy. Ann Intern Med 102:596–602, 1985Google Scholar
  8. 8.
    Klimo P, Connors JM: MACOP-B Chemotherapy for the Treatment of Diffuse Large-Cell Lymphoma. Ann Intern Med 102:596–602, 1985Google Scholar
  9. 9.
    Double JC, Brown JR: Evaluation of the binding of some substituted antraquinones and naphtaacenequinones to DNA. J Pharmacol 28:166–169, 1976Google Scholar
  10. 10.
    Coltman CA Jr, Coltman TM, Balcerzak SP, Morrison FS, Von Hoff DD: Mitoxantrone in refractory non-Hodgkin lymphoma, A Southwest Oncology Group Study. Seminars in Oncology, Vol 11, 3:50–53, 1984Google Scholar
  11. 11.
    Gams RA, Bryan S, Dukart G, Weiss A, Case D, Jones S, Stein R: Mitoxantrone in malignant lymphoma. Invest New Drugs 3:219–222, 1985Google Scholar
  12. 12.
    Dukart G, Iatropulos MJ, Yacobi A: Comment on mitoxantrone, Drug Intelligence and Clinical Pharmacy, 19:216–218, 1985Google Scholar
  13. 13.
    Posner LE, Dukart G, Goldberg T, Bernstein T, Cartwright K: Mitoxantrone: an overview of safety and toxicity. Invest New Drugs 3:123–132, 1985Google Scholar
  14. 14.
    Gaver RC, Deeb G, Pittman KA, Issel BF, Mittelman A, Smyth RD: Disposition of orally administered 14 C-prednimustine in cancer patients. Cancer Chemother Pharmacol 11:139–143, 1983Google Scholar
  15. 15.
    Newell DR, Shepherd CR, Harrap KR: The pharmaco-kinetics of prednimustine and chlorambucil in the rat. Cancer Chemother Pharmacol 6:85–91, 1981Google Scholar
  16. 16.
    Lober J, Mouridsen HT, Christiansen IE, Dombernowsky P, Mattsson W, Rorth M: A Phase III trial comparing prednimustine (Leo 1031) to chlorambucil plus prednisolone in advanced breast cancer. Cancer 52:1570–1576, 1983Google Scholar
  17. 17.
    Håkansson L, Könyves I, Landberg T, Lindberg L-G, Möller T: Continuous treatment of non-Hodgkin's malignant lymphoma with prednimustine (Leo 1031). Oncology 35(3):103–106, 1978Google Scholar
  18. 18.
    Pedersen-Bjergaard J, Mørk-Hansen M, Geisler CH, Nissen NI: Clinical trial of prednimustine, Leo 1031 (NSC-134087) in patients with non-Hodgkin's lymphomata and chronic lymphocytic leukemia previously treated with steroids and alkylating agents. Acta Med Scand 207: 215–220, 1980Google Scholar
  19. 19.
    Lennert K, Mohri N, Stein H, Kaisering E: The histopathology of malignant lymphoma. Brit J Haematol Suppl 31:193, 1975Google Scholar
  20. 20.
    Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M: Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res 31:1860–1861, 1971PubMedGoogle Scholar
  21. 21.
    WHO Handbook for Reporting Results of Cancer Treatment, WHO Offset Publication No 48, Geneva, 1979Google Scholar
  22. 22.
    Alexander J, Dainiak N, Berger HJ, Goldman L, Johnstone D, Reduto L, Duffy T, Schwartz P, Gottschalk A, Zaret BL: Serial assessment of doxorubicin cardiotoxicity with quantitative radionuclide angiocardiography. N Engl J Med 300:278–283, 1979Google Scholar
  23. 23.
    UICC Technical Report Series — Volume 56: Manual of Cancer Chemotherapy, Chapter 3. Monfardini S, Brunner K, Crowther D, Olive D, MacDonald J, Eckhardt S, Whitehouse J (eds) with the collaboration of Reed D; 3rd edition, UICC, Geneva, 1981Google Scholar
  24. 24.
    Landys K: A New Trephine for Closed Bone Marrow Biopsy. Acta Haemal 64:216–220, 1980Google Scholar
  25. 25.
    Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SW, Mantel N, McPherson K, Peto J, Smith PG: Design and analysis of randomized clinical trials requiring prolonged observation of each patient, II. Analysis and examples. Br J Cancer 35:1–39, 1977PubMedGoogle Scholar
  26. 26.
    Newland AC, Jones L, Cotter FE: Mitozantrone in combination in refractory and relapsed non-Hodgkin's lymphoma. Meeting Abstracts, 4th International Symposium on Therapy of Acute Leukemias (Symposium Novantrone) p 16, Rome, February, 1987Google Scholar
  27. 27.
    Brussalimo E, Bertini M, Guidi S, Vitolo U, Inverardi D, Merante S, Resegotti L, Bernasconi C, Rossi Ferrini PL, Cametti G, Canta M: CHOP versus CNOP in non-Hodgkin lymphoma: Comparison of response and toxicity, Meeting Abstracts, 4th International Symposium on Therapy of Acute Leukemias (Symposium Novantrone) p 18, Rome, February, 1987Google Scholar
  28. 28.
    Poirier TI: Mitoxantrone. Drug Intell Clin Pharm 20:97–105, 1986Google Scholar

Copyright information

© Kluwer Academic Publishers 1988

Authors and Affiliations

  • Karl E. Landys
    • 1
  1. 1.Department of OncologySahlgren's HospitalGothenburgSweden

Personalised recommendations