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Concurrent chemoradiotherapy followed by l-asparaginase-containing chemotherapy, VIDL, for localized nasal extranodal NK/T cell lymphoma: CISL08-01 phase II study

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We conducted a phase II trial of concurrent chemoradiotherapy (CCRT) followed by 2 cycles of l-asparaginase-containing chemotherapy for patients who were newly diagnosed with stages IE and IIE nasal extranodal NK/T cell lymphoma (ENKTL). CCRT consisted of 40–44 Gy of radiotherapy with weekly administration of 30 mg/m2 of cisplatin for 4 weeks. Two cycles of VIDL (etoposide (100 mg/m2), ifosfamide (1,200 mg/m2), and dexamethasone (40 mg) from days 1 to 3, and l-asparaginase (4,000 IU/m2) every other day from days 8 to 20) were administered sequentially. CCRT yielded a 90 % overall response rate without significant side effects in 30 patients, including 20 patients with complete response (CR); however, two patients showed distant disease progression. After CCRT, VIDL chemotherapy showed an 87 % final CR rate (26/30). Although grade III or IV hematologic toxicity was frequent during VIDL chemotherapy, no treatment-related mortality was observed, and l-asparaginase-associated toxicity was manageable. With a median follow-up of 44 months, 11 patients showed local (n = 4) and distant (n = 7) relapse or progression. The estimated 5-year progression-free and overall survival rates were 73 and 60 %, respectively. In conclusion, CCRT followed by l-asparaginase-containing chemotherapy is a feasible treatment for newly diagnosed stages IE/IIE nasal ENKTL.

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  1. Lee J, Suh C, Park YH, Ko YH, Bang SM, Lee JH, Lee DH, Huh J, Oh SY, Kwon HC, Kim HJ, Lee SI, Kim JH, Park J, Oh SJ, Kim K, Jung C, Park K, Kim WS (2006) Extranodal natural killer T-cell lymphoma, nasal-type: a prognostic model from a retrospective multicenter study. J Clin Oncol 24:612–618

    Article  PubMed  Google Scholar 

  2. Au WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Sng I, Vose J, Armitage JO, Liang R (2009) Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project. Blood 113:3931–3937

    Article  PubMed  CAS  Google Scholar 

  3. Lee J, Park YH, Kim WS, Lee SS, Ryoo BY, Yang SH, Park KW, Kang JH, Park JO, Lee SH, Kim K, Jung CW, Park YS, Im YH, Kang WK, Lee MH, Ko YH, Ahn YC, Park K (2005) Extranodal nasal type NK/T-cell lymphoma: elucidating clinical prognostic factors for risk-based stratification of therapy. Eur J Cancer 41:1402–1408

    Article  PubMed  Google Scholar 

  4. Kim WS, Song SY, Ahn YC, Ko YH, Baek CH, Kim DY, Yoon SS, Lee HG, Kang WK, Lee HJ, Park CH, Park K (2001) CHOP followed by involved field radiation: is it optimal for localized nasal natural killer/T-cell lymphoma? Ann Oncol 12:349–352

    Article  PubMed  CAS  Google Scholar 

  5. Kim GE, Cho JH, Yang WI, Chung EJ, Suh CO, Park KR, Hong WP, Park IY, Hahn JS, Roh JK, Kim BS (2000) Angiocentric lymphoma of the head and neck: patterns of systemic failure after radiation treatment. J Clin Oncol 18:54–63

    PubMed  CAS  Google Scholar 

  6. Kim SJ, Kim K, Kim BS, Kim CY, Suh C, Huh J, Lee SW, Kim JS, Cho J, Lee GW, Kang KM, Eom HS, Pyo HR, Ahn YC, Ko YH, Kim WS (2009) Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell Lymphoma: Consortium for Improving Survival of Lymphoma study. J Clin Oncol 27:6027–6032

    Article  PubMed  CAS  Google Scholar 

  7. Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, Ishizawa K, Maseki N, Itoh K, Usui N, Wasada I, Kinoshita T, Ohshima K, Matsuno Y, Terauchi T, Nawano S, Ishikura S, Kagami Y, Hotta T, Oshimi K (2009) Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211. J Clin Oncol 27:5594–5600

    Article  PubMed  CAS  Google Scholar 

  8. Jaccard A, Gachard N, Marin B, Rogez S, Audrain M, Suarez F, Tilly H, Morschhauser F, Thieblemont C, Ysebaert L, Devidas A, Petit B, de Leval L, Gaulard P, Feuillard J, Bordessoule D, Hermine O (2011) Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood 117:1834–1839

    Article  PubMed  CAS  Google Scholar 

  9. Yamaguchi M, Kwong YL, Kim WS, Maeda Y, Hashimoto C, Suh C, Izutsu K, Ishida F, Isobe Y, Sueoka E, Suzumiya J, Kodama T, Kimura H, Hyo R, Nakamura S, Oshimi K, Suzuki R (2011) Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study. J Clin Oncol 29:4410–4416

    Article  PubMed  CAS  Google Scholar 

  10. Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS (2012) SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood 120:2973–2980

    Article  PubMed  CAS  Google Scholar 

  11. Lee J, Au WY, Park MJ, Suzumiya J, Nakamura S, Kameoka J, Sakai C, Oshimi K, Kwong YL, Liang R, Yiu H, Wong KH, Cheng HC, Ryoo BY, Suh C, Ko YH, Kim K, Lee JW, Kim WS, Suzuki R (2008) Autologous hematopoietic stem cell transplantation in extranodal natural killer/T cell lymphoma: a multinational, multicenter, matched controlled study. Biol Blood Marrow Transplant 14:1356–1364

    Article  PubMed  Google Scholar 

  12. Kim SJ, Oh SY, Hong JY, Chang MH, Lee DH, Huh J, Ko YH, Ahn YC, Kim HJ, Suh C, Kim K, Kim WS (2010) When do we need central nervous system prophylaxis in patients with extranodal NK/T-cell lymphoma, nasal type? Ann Oncol 21:1058–1063

    Article  PubMed  CAS  Google Scholar 

  13. (1993) A predictive model for aggressive non-Hodgkin’s lymphoma. The international non-hodgkin's lymphoma prognostic factors project. N Engl J Med 329:987-994

  14. Kim TM, Park YH, Lee SY, Kim JH, Kim DW, Im SA, Kim TY, Kim CW, Heo DS, Bang YJ, Chang KH, Kim NK (2005) Local tumor invasiveness is more predictive of survival than International Prognostic Index in stage I(E)/II(E) extranodal NK/T-cell lymphoma, nasal type. Blood 106:3785–3790

    Article  PubMed  CAS  Google Scholar 

  15. Kim HS, Kim KH, Chang MH, Ji SH, Lim Do H, Kim K, Kim SJ, Ko Y, Ki CS, Jo SJ, Lee JW, Kim WS (2009) Whole blood Epstein-Barr virus DNA load as a diagnostic and prognostic surrogate: extranodal natural killer/T-cell lymphoma. Leuk Lymphoma 50:757–763

    Article  PubMed  CAS  Google Scholar 

  16. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17:1244

    PubMed  CAS  Google Scholar 

  17. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10

    Article  PubMed  CAS  Google Scholar 

  18. Kim SJ, Kim WS (2010) Treatment of localized extranodal NK/T cell lymphoma, nasal type. Int J Hematol 92:690–696

    Article  PubMed  CAS  Google Scholar 

  19. Kim SJ, Park Y, Kim BS, Kim I, Ko YH, Kim WS (2012) Extranodal natural killer/T-cell lymphoma with long-term survival and repeated relapses: does it indicate the presence of indolent subtype? Korean J Hematol 47:202–206

    Article  PubMed  PubMed Central  Google Scholar 

  20. Au WY, Kim SJ, Yiu HH, Ngan RK, Loong F, Kim WS, Kwong YL (2010) Clinicopathological features and outcome of late relapses of natural killer cell lymphomas 10-29 years after initial remission. Am J Hematol 85:362–363

    PubMed  Google Scholar 

  21. Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, Ishizawa K, Maseki N, Itoh K, Usui N, Wasada I, Kinoshita T, Hotta T, Tsukasaki K, Oshimi K (2012) Concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: an updated analysis of the Japan clinical oncology group study JCOG0211. J Clin Oncol 30:4044–4046

    Article  PubMed  Google Scholar 

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Correspondence to Won Seog Kim.

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Kim, S.J., Yang, DH., Kim, J.S. et al. Concurrent chemoradiotherapy followed by l-asparaginase-containing chemotherapy, VIDL, for localized nasal extranodal NK/T cell lymphoma: CISL08-01 phase II study. Ann Hematol 93, 1895–1901 (2014).

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