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Deoxycoformycin-Containing Combination Chemotherapy for Adult T-Cell Leukemia-Lymphoma: Japan Clinical Oncology Group Study (JCOG9109)

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Abstract

Aggressive adult T-cell leukemia-lymphoma (ATL) generally has a very poor prognosis. Deoxycoformycin (DCF, pentostatin), an inhibitor of adenosine deaminase, has shown promising therapeutic efficacy for ATL. To develop a new effective therapy against aggressive ATI., we carried out a multicenter phase II study of DCF-containing combination chemotherapy. Sixty-two previously untreated patients with ATL (34, 21, and 7 patients with diseases of the acute, lymphoma, and unfavorable chronic types, respectively) were enrolled, but 2 were ineligible because they were judged to be favorable chronic types. A regimen of 1 mg/m2 vincristine intravenously on days 1 and 8, 40 mg/m2 doxorubicin intravenously on day 1,100 mg/m2 etoposide intravenously on days 1 through 3, 40 mg/m2 prednisolone orally on days 1 and 2, and 5 mg/m2 DCF intravenously on days 8,15, and 22 was administered every 28 days for 10 cycles unless disease progression or toxic complications occurred. Fifty-two percent of 60 eligible patients responded (95% confidence interval [CI], 38%-65%), with 17 patients (28%) achieving a complete response (CR) (95% CI, 17%-41%) and 14 achieving a partial response. The CR rate was inferior to those of both the previous Japan Clinical Oncology Group (JCOG) study (JCOG8701, 43%), a 9-drug combination chemotherapy of the second generation, and the subsequent JCOG9303 study (35%), a granulocyte colony-stimulating factor-supported, dose-intensified, 9-drug regimen. The median survival time of the 60 eligible patients in JCOG9109 was 7.4 months, and the estimated 2-year survival rate was 15.5%; these results were identical with those of JCOG8701 but inferior to those of JCOG9303. Grade 4 neutropenia and infection of grade 3 or greater were frequent (67% and 22%, respectively), and treatment-related death was observed in 4 patients (7%), scpticcmia in 2, and cytomcgalovirus pneumonia in 2. We conclude that DCF-containing combination chemotherapy is not a promising regimen against aggressive ATL.

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References

  1. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H. Adult T-cell leukemia: clinical and hématologie features of 16 cases.Blood. 1977;50:481–492.

    PubMed  CAS  Google Scholar 

  2. Yoshida M, Miyoshi I, Hinuma Y. Isolation and characterization of retrovirus from cell lines of human adult T cell leukemia and its implication in the disease.Proc Natl Acad Sei 11 S A. 1982;79:2031–2035.

    Article  CAS  Google Scholar 

  3. Shimoyama M. Diagnostic criteria and classification of clinical sub-types of adult T-cell leukaemia-lymphoma: a report from the Lymphoma Study Group (1984–87).Br J Haematol. 1991;79:428–437.

    Article  CAS  PubMed  Google Scholar 

  4. Pawson R, Mufti GJ, Pagliuca A. Management of adult T-cell lcukacmia/lyraphoraa.Br J Haematol. 1998;100:453–458.

    Article  CAS  PubMed  Google Scholar 

  5. Tobinai K. Adult T-cell lcukcmia-lymphoma. In: Abeloff MD, Arraitagc JO, Lichter AS, Nicdcrhubcr JE. eds.Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000:2748–2768.

    Google Scholar 

  6. Shimoyama M. Chemotherapy of ATL. In: Takatsuki K, ed.Adult T-cell Leukemia. Oxford, UK: Oxford University Press; 1994:221–237.

    Google Scholar 

  7. Kuwazuru Y, Hanada S, Furukawa T, et al. Expression of P-glycoprotein in adult T-cell leukemia cells.Blood. 1990;76:2065–2071.

    PubMed  CAS  Google Scholar 

  8. Tkeda K, Oka M, Yamada Y, et al. Adult T-celI leukemia cells overexpress the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes.M J Cancer. 1999;82:599–604.

    Google Scholar 

  9. Tsukasaki K, Koeffler P, Tomonaga M. Human T-lymphotropic virus type 1 infection.Baillieres Best Pract Res Clin Haematol. 2000;13:231–243.

    Article  CAS  PubMed  Google Scholar 

  10. Grever M, Kopecky K, Foucar MK, et al. Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study.J Clin Oncol. 1995;13:974–982.

    Article  CAS  PubMed  Google Scholar 

  11. Flinn IW, Kopecky KJ, Foucar MK, et al. Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin.Blood. 2000;96:2981–2986.

    PubMed  CAS  Google Scholar 

  12. Mercieca J, Matutes E, Dearden C, MacLenn an K, Catovsky D. The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype.J. Clin Oncol. 1994;12:2588–2593.

    Article  CAS  PubMed  Google Scholar 

  13. Ho AD, Suciu S, Stryckmans P, et al. Pentostatin in T-cell malignancies: a phase II trial of the EORTC Leukemia Cooperative Group.Ann Oncol. 1999;10:1493–1498.

    Article  CAS  PubMed  Google Scholar 

  14. Kurzrock R, Pilat S, Duvic M. Pentostatin therapy of T-cell lymphomas with cutaneous manifestations.J. Clin Oncol. 1999;17:3117–321.

    Article  CAS  PubMed  Google Scholar 

  15. Grever MR, Siaw ME, Jacob WE, et al. The biochemical and clinical consequences of 2’-deoxycoformycin in refractory lymphoproliferative malignancy.Blood. 1981;57:406–417.

    PubMed  CAS  Google Scholar 

  16. de Körte D, Haverkort WA, van Leeuwen EF, Roos D, van Gennip AH. Biochemical consequences of 2’-deoxycoformycin treatment in a patient with T-cell lymphoma: some unusual findings.Cancer. 1987;60:750–755.

    Article  PubMed  Google Scholar 

  17. Major PP, Agarwal RP, Kufe DW. Clinical pharmacology of deoxycoformycin.Blood. 1981;58:91–96.

    PubMed  CAS  Google Scholar 

  18. Daenen S, Rojer RA, Smit JW, Halie MR, Nieweg HO. Successful chemotherapy with deoxycoformycin in adult T-cell lymphomaleukaemia.Br.I Haematol 1984;58:723–727.

    Article  CAS  Google Scholar 

  19. Yamaguchi K, Yul LS, Oda T, et al. Clinical consequences of 2’-deoxycoformycin treatment in patients with refractory adult T-cell leukaemia.Leuk Res. 1986;10:989–993.

    Article  CAS  PubMed  Google Scholar 

  20. Lofters W, Campbell M, Gibbs WN, Cheson BD. 2’-Deoxycoformycin therapy in adult T-cell leukemia/lymphoma.Cancer. 1987;60:2605–2608.

    Article  CAS  PubMed  Google Scholar 

  21. Tobinai K, Shimoyama M, Inoue S, et al. Phase I study of YK-176 (2’-deoxycoformycin) in patients with adult T-cell leukemia-lymphoma: the DCF Study Group.Jpn J Clin Oncol. 1992;22:164–171.

    PubMed  CAS  Google Scholar 

  22. Kodama K, Kusakabe H, Machida H, et al. Isolation of 2’-deoxycoformycin and cordyceptin from wheat bran culture ofAspergillus nidulans Y 176-2.Agric Biol Chem. 1979;43:2375–2377.

    CAS  Google Scholar 

  23. Gryn J, Gordon R, Bapat A, Goldman N, Goldberg J. Pentostatin increases the acute toxicity of high dose cyclophosphamide.Bone Marrow Transplant. 1993;12:217–220.

    PubMed  CAS  Google Scholar 

  24. Tobinai K, Shimoyama M, Minato K, et al. Japan Clinical Oncology Group phase II trial of second-generation “LSG4 protocol” in aggressive T- and B-lymphoma: a new predictive model forT-and B~lymphoma [abstract].Proc Am Soc Clin Oncol. 1994;13:378.

    Google Scholar 

  25. Wilson WH, Bryant G, Bates S, et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin’s lymphoma.J. Clin Oncol. 1993;11:1573–1582.

    Article  CAS  PubMed  Google Scholar 

  26. Velasquez WS, McLaughlin P,Tucker S, et al. ESHAP—an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study.Clin Oncol. 1994;12:1169–1176.

    Article  CAS  Google Scholar 

  27. Tanaka K, Rgami K, Nakamura E, et al. A case of ATI, presenting a huge intrahepatic tumor, abated with etoposide (NK-171) therapy alone [in Japanese].Rinsho Kelsueki. 1987;28:392–397.

    CAS  Google Scholar 

  28. Wakui A, YokoyamaM.Takahashi H, et al. A phase I study of VP-16-213 (VP, etoposide) by single and 5-day intravenous administration [in Japanese],Can To Kagaku Ryoho. 1986;13:319–329.

    CAS  Google Scholar 

  29. Naito K, Kobayashi M, Oyama A, et al. Phase II study of carbo-platin in malignant lymphoma [in Japanese].Gan To Kagaku Ryoho. 1988;15:2145–2151.

    PubMed  CAS  Google Scholar 

  30. Oken MM, Creech RII, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group.Am J Clin Oncol. 1982;5:649–655.

    Article  CAS  PubMed  Google Scholar 

  31. Shimoyama M, Fukuda H, Saijo N, Yamaguchi N. Japan Clinical Oncology Group (JCOG).Jpn J Clin Oncol. 1998;28:158–162.

    Article  CAS  PubMed  Google Scholar 

  32. World Health Organization.WHO Handbook for Reporting Results of Cancer Treatment. Geneva, Switzerland: World Health Organization; 1979. WHO Offset Publication No. 48.

    Google Scholar 

  33. Yamada Y,Tomonaga M, Fukuda H, et al. A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukaemia-lymphoma: Japan Clinical Oncology Group Study 9303.Br.1 Haematol. 2001;113:375–382.

    Article  CAS  Google Scholar 

  34. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations.J am Stat Assoc. 1958;53:157–181.

    Article  Google Scholar 

  35. Shimoyama M, Ota K, Kikuchi M, et al. Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin’s lymphoma treated with VEPA or VEPA-M.J. Clin Oncol. 1988;6:128–141.

    Article  CAS  PubMed  Google Scholar 

  36. Shimoyama M, Ota K, Kikuchi M, et al. Major prognostic factors of adult patients with advanced T-cell Iymphoma/leukemia.J. Clin Oncol. 1988;6:1088–1097.

    Article  CAS  PubMed  Google Scholar 

  37. Fisher RI, Gaynor ER, Dah Iberg S, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma.N Engl J Med. 1993;328:1002–1006.

    Article  CAS  PubMed  Google Scholar 

  38. Urba WJ, Baseler MW, Kopp WC, et al. Deoxycoformycin-induced immunosuppression in patients with hairy cell leukemia.Blood. 1989;73:38–46.

    PubMed  CAS  Google Scholar 

  39. Waldmann TA, White JD, Goldman CK, et al. The interleukin-2 receptor: a target for monoclonal antibody treatment of human T-cell lymphotropic virus I-induced adult T-cell leukemia.Blood. 1993;82:1701–1712.

    PubMed  CAS  Google Scholar 

  40. Waldmann TA, White JD, Carrasquillo JA, et al. Radioim-munothcrapy of intcrlcukin-2R a-expressing adult T-cell leukemia with yttrium-90-labeled anti-Tac.Blood. 1995;86:4063–4075.

    PubMed  CAS  Google Scholar 

  41. 41. Sparano JA, Wiernik PH, Strack M, Leaf A, Becker N, Valentine ES. Infusional cyclophosphamide, doxorubicin, and etoposide in human immunodeficiency virus- and human T-cell leukemia virus type I-related non-Hodgkin’s lymphoma: a highly active regimen.Blood. 1993;81:2810–2815.

    PubMed  CAS  Google Scholar 

  42. Taguchi H, Kinoshita K, Takatsuki K, et al. An intensive chemotherapy of adult T-cell leukemia/lymphoma: CHOP followed by etoposide, vindesine, ranimustine, and mitoxantrone with granulocyte colony-stimulating factor support.J Acquir Immune Defic Syndr Him Retroviral. 1996;12:182–186.

    Article  CAS  Google Scholar 

  43. Utsunomiya A, Miyazaki Y,Takatsuka Y, et al. Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation.Bone Marrow Transplant. 2001;27:15–20.

    Article  CAS  PubMed  Google Scholar 

  44. Abe Y, Yashiki S, Choi I, et al. Eradication of virus-infected T-cells in a case of adult T-cell leukemia/lymphoma by nonmyeloablative peripheral blood stem cell transplantation with conditioning consisting of low-dose total body irradiation and pentostatin.Int J Hematol. 2002;76:91–93.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Nagasaki University, Nagasaki

    Kunihiro Tsukasaki, Yasuaki Yamada & Masao Tomonaga

  2. National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, 104-0045, Tokyo, Japan

    Kensci Tobinai & Masanori Shimoyama

  3. National Kyusyu Cancer Center, Fukuoka

    Mitsuo Kozuru & Naokuni Uikc

  4. University of the Ryukyus, Naha

    Koichi Araki

  5. Sapporo Hokuyu Hospital, Sapporo

    Masaharu Kasai

  6. Kumamoto University, Kumamoto

    Kiyoshi Takatsuki

  7. Kagoshima Municipal Hospital, Kagoshima

    Mitsutoshi Tara

  8. Sapporo National Hospital, Sapporo

    Chikara Mikuni

  9. Nagoya University, Nagoya, Japan

    Tomomitsu Hotta

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  1. Kunihiro Tsukasaki
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  2. Kensci Tobinai
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Members of the Lymphoma Study Group (LSG) of the Japan Clinical Oncology Group (JCOG)

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Correspondence to Kensci Tobinai.

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Tsukasaki, K., Tobinai, K., Shimoyama, M. et al. Deoxycoformycin-Containing Combination Chemotherapy for Adult T-Cell Leukemia-Lymphoma: Japan Clinical Oncology Group Study (JCOG9109). Int J Hematol 77, 164–170 (2003). https://doi.org/10.1007/BF02983215

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