Abstract
Purpose: To evaluate the response and side effects of combination therapy with low dose CHOP chemotherapy and mitoguazone dihydrochloride in patients with non-Hodgkin's lymphoma associated with the acquired immunodeficiency syndrome (AIDS-NHL). Methods: Eighteen patients newly diagnosed with intermediate or high-grade AIDS-NHL were treated with low dose CHOP as follows: day 1, cyclophosphamide 350mg/m2, intravenously (IV); doxorubicin 25mg/m2 IV; vincristine 2mg IV; and prednisone 100mg given orally on days 1 through 5. In addition, mitoguazone dihydrochloride was given at a dose of 600mg/m2 IV on days 1 and 15 of each 28-day treatment cycle. Results: Seventeen males and one female patient were accrued. Twelve patients had high-grade pathologies while the remainder had an intermediate grade pathology (diffuse large cell). The median CD4+ lymphocyte count was 98/dl (range 1–924). Three patients (17%) reported an AIDS-defining illness prior to lymphoma diagnosis. Of 14 evaluable patients, 6 (43%) achieved a complete remission and 5 (35%) a partial remission. The median failure free and overall survival times were 6.5 and 8.4 months, respectively. Major toxicity was hematologic with grade 3 or 4 neutropenia in 72%; two patients died of neutropenic sepsis. Conclusions: Mitoguazone in combination with low dose CHOP is a safe regimen, associated with a response rate of 79% (CR 43%, PR 36%, 95% CI=49–95%). These preliminary results suggest no major improvement in terms of response over use of CHOP without mitoguazone.
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References
Centers for Disease Control. Revision of the case definition of acquired immunodeficiency syndrome for national reported: United States. Ann Intern Med 103: 402–403, 1985
Beral V, Peterman T, Berkelman R, Jaffe H: AIDS associated non-Hodgkin's lymphoma. Lancet 337: 805–809, 1991
Pluda JM, Yarchoan R, Jaffe ES et al.: Development of non-Hodgkin's lymphoma in a cohort of patients with severe human immunodeficiency virus (HIV) infection on long term antiretroviral therapy. Ann Intern Med 113: 276, 1990
Ziegler JL, Beckstead JA, Volberding PA et al.: Non-Hodgkin's lymphomas in 90 homosexual men: Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. N Engl J Med 311: 565–570, 1984
Levine AM: AIDS-related lymphoma. Blood 80: 8–20, 1992
Levine AM, Wernz JC, Kaplan L et al.: Low dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance in AIDS-related lymphoma. JAMA 226: 84–88, 1991
Kaplan L, Straus D, Testa M et al.: Low-dose compared with standard-dose mBACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. N Engl J Med 23: 1641–1648, 1997
Sparano JA, Wiernik PH, Hu Xiaoping et al.: Pilot trial of infusional cyclophosphamide, doxorubicin, and etoposide plus didanosine and filgrastrim in patients with human immunodeficiency virus-associated non-Hodgkin's lymphoma. J Clin Oncol 14: 3026–3035, 1996
Warrell RP, Burchenal JH: Methylglyoxal-bis(guanylhydrazone) (methyl-GAG): Current studies and future prospects. J Clin Oncol 1: 52–65, 1983
Levine AM, Tulpule A, Tessman D et al.: Mitoguazone therapy in patients with refractory or relapsed AIDS-related lymphoma: Results from a multicenter Phase II Trial. J Clin Oncol 15: 1094–1103, 1997
Rizzo J, Levine A, Weiss GR et al.: Pharmacokinetic profile of mitoguazone (MGBG) in patients with AIDS-related non-Hodgkin's lymphoma. Invest New Drugs 14: 227–234, 1996
Green S, Weiss GR: Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs 10: 239–253, 1992
Kalbfleisch JD, Prentice RL: The Statistical Analysis of Failure Time Data. John Wiley and Sons, New York 1980
Mehta CR, Patel NR: A network algorithm for performing Fisher's exact test in r x c contingency tables. J Am Stat Assoc 78: 427–434, 1983
Minitab Reference Manual. PC Version, Release 8. (PA): Minitab Inc, State College, PA, 1991
Gill PS, Levine AM, Krailo M et al.: AIDS-related malignant lymphoma: Results of prospective treatment trials. J Clin Oncol 5: 1322–1328, 1987
Levine AM, Sullivan-Halley J, Pike MC et al.: Human immunodeficiency virus-related lymphoma. Prognostic factors predictive of survival. Cancer 68: 2466–2472, 1991
Gisselbrecht C, Oksenhendler E, Tirelli U et al.: Human immunodeficiency virus-related lymphoma treated with intensive combination chemotherapy. Am J Med 95: 188–196, 1993
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Tulpule, A., Espina, B.M., Pedro Santabarbara, A.B. et al. Treatment of AIDS Related Non-Hodgkin's Lymphoma with Combination Mitoguazone Dihydrochloride and Low Dose Chop Chemotherapy: Results of a Phase II study. Invest New Drugs 22, 63–68 (2004). https://doi.org/10.1023/B:DRUG.0000006175.32100.2c
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DOI: https://doi.org/10.1023/B:DRUG.0000006175.32100.2c