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01-02-2015 | Original Paper

Trial of LVDP regimen (l-asparaginase, etoposide, dexamethasone, and cisplatin, followed by radiotherapy) as first-line treatment for newly diagnosed, stage III/IV extranodal natural killer/T cell lymphoma

Authors: Y. Q. Wang, Y. Yang, H. Y. Zhuo, L. Q. Zou, Y. Jiang, M. Jiang

Published in: Medical Oncology | Issue 2/2015

Abstract

Stage III/IV extranodal natural killer/T cell lymphoma (ENKL) has a poor response and poor survival. Given the sensitivity of ENKL to radiotherapy and the fact that there is no consensus on standard chemotherapy, we conducted a clinical trial of LVDP regimen, combining LVDP chemotherapy (containing etoposide, dexamethasone, l-asparaginase, and cisplatin), followed by radiotherapy as a consolidation therapy regimen, for newly diagnosed patients with stage III/IV ENKL to evaluate the efficacy and safety of this regimen. The primary endpoints were overall response rate (ORR) and survival [overall survival (OS) and progression-free survival (PFS)] at 1 or 2 years, while the secondary endpoints were toxicity and adverse effects. In total, 18 patients were enrolled in this trial from July 2010 to September 2013. The mean completed cycles of chemotherapy was 4.04 (range 1–8 cycles), and the ORR was 50 %. During a mean follow-up of 21.8 months (range 2–51 months), the 1-year OS and PFS rates were 72.2 and 50.0 %, respectively, the 2-year OS and PFS rates were 33.3 and 22.2 %, respectively, and the median OS and PFS were 23.0 and 10.5 months, respectively. Severe adverse effects during therapy included six cases of grade 3/4 bone marrow suppression and one case of grade 3 transaminase increase. Sex, eastern cancer oncology group, performance status, Korean Prognostic Index, International Prognostic index, and bone marrow infiltration may influence the prognosis of advanced-stage ENKL.

Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the clinical advisory committee meeting—Airlie house, virginia, November 1997. J Clin Oncol. 1999;17(12):3835–49.PubMed

Au WY, Ma SY, Chim CS, Choy C, Loong F, Lie AKW, et al. Clinicopathologic features and treatment outcome of mature T-cell and natural killer-cell lymphomas diagnosed according to the World Health Organization classification scheme: a single center experience of 10 years. Ann Oncol. 2005;16(2):206–14. doi:10.1093/annonc/mdi037.PubMedCrossRef

Harris ME. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26:4124–30.CrossRef

Au WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Sng I, et al. 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. 2009;113(17):3931–7. doi:10.1182/blood-2008-10-185256.PubMedCrossRef

Lin NJ, Song YQ, Zheng W, Tu MF, Xie Y, Wang XP, et al. A prospective phase II study of l-asparaginase- CHOP plus radiation in newly diagnosed extranodal NK/T-cell lymphoma, nasal type. J Hematol Oncol. 2013;. doi:10.1186/1756-8722-6-44.

Li YX, Yao B, Jin J, Wang WH, Liu YP, Song YW, et al. Radiotherapy as primary treatment for stage IE and IIE nasal natural killer/T-cell lymphoma. J Clin Oncol. 2006;24(1):181–9. doi:10.1200/jco.2005.03.2573.PubMedCrossRef

Li Y-X, Wang H, Jin J, Wang W-H, Liu Q-F, Song Y-W, et al. Radiotherapy alone with curative intent in patients with stage I extranodal nasal-type NK/T-cell lymphoma. Int J Radiat Oncol Biol Phys. 2012;82(5):1809–15.PubMedCrossRef

Deng T, Zhang C, Zhang X, Wu S, Xu Y, Liu S, et al. Treatment outcome of radiotherapy alone versus radiochemotherapy in IE/IIE extranodal nasal-type natural killer/T cell lymphoma: a meta-analysis. PloS One. 2014;. doi:10.1371/journal.pone.0106577.

Cheung MMC, Chan JKC, Lau WH, Ngan RKC, Foo WWL. Early stage nasal NK/T-cell lymphoma: Clinical outcome, prognostic factors, and the effect of treatment modality. Int J Radiat Oncol Biol Phys. 2002;54(1):182–90. doi:10.1016/s0360-3016(02)02916-4.PubMedCrossRef

10.

Lee J, Suh C, Kang H, Ryoo B-Y, Huh J, Ko Y, et al. Phase I study of proteasome inhibitor bortezomib plus CHOP in patients with advanced, aggressive T-cell or NK/T-cell lymphoma. Ann Oncol. 2008;19(12):2079–83.PubMedCentralPubMedCrossRef

11.

Kwong YL, Yamaguchi M, Suzuki R, Kim WS, Hasegawa Y, Izutsu K, et al. Phase I study of smile chemotherapy for advanced-stage or relapsed/refractory extranodal NK/T-cell lymphoma/leukemia. Haematologica Hematol J. 2007;92:109.

12.

Kwong YL, Yamaguchi M, Maeda Y, Hashimoto C, Kim WS, Suh CW, et al. 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. Haematologica Hematol J. 2010;95:119–20.CrossRef

13.

Kwong Y-L, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, et al. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012;120(15):2973–80.PubMedCrossRef

14.

Yang L, Liu H, Xu X, Wang X, Huang H, Shi W, et al. Retrospective study of modified SMILE chemotherapy for advanced-stage, relapsed, or refractory extranodal natural killer (NK)/T cell lymphoma, nasal type. Med oncol. 2013;30(4):720. doi:10.1007/S12032-013-0720-7.PubMedCrossRef

15.

Yong W, Zheng W, Zhu J, Zhang Y, Wang X, Xie Y, et al. l-Asparaginase in the treatment of refractory and relapsed extranodal NK/T-cell lymphoma, nasal type. Ann Hematol. 2009;88(7):647–52. doi:10.1007/s00277-008-0669-3.PubMedCrossRef

16.

Kim B-S, Kim D-W, Im S-A, Kim C, Kim T-Y, Yoon S-S, et al. Effective second-line chemotherapy for extranodal NK/T-cell lymphoma consisting of etoposide, ifosfamide, methotrexate, and prednisolone. Ann Oncol. 2009;20(1):121–8.PubMedCrossRef

17.

Yamaguchi M, Kwong Y-L, Kim WS, Maeda Y, Hashimoto C, Suh C, et al. 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. 2011;29(33):4410–6. doi:10.1200/jco.2011.35.6287.PubMedCrossRef

18.

Huang M-J, Jiang Y, Liu W-P, Li Z-P, Li M, Zhou L, et al. Early or up-front radiotherapy improved survival of localized extranodal NK/T-cell lymphoma, nasal-type in the upper aerodigestive tract. Int J Radiat Oncol Biol Phys. 2008;70(1):166–74. doi:10.1016/j.ijrobp.2007.05.073.PubMedCrossRef

19.

Kim SJ, Kim WS. Treatment of localized extranodal NK/T cell lymphoma, nasal type. Int J Hematol. 2010;92(5):690–6. doi:10.1007/s12185-010-0720-8.PubMedCrossRef

20.

Jiang M, Zhang H, Jiang Y, Yang QP, Xie L, Liu WP, et al. Phase 2 trial of “Sandwich” l-asparaginase, vincristine, and prednisone chemotherapy with radiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma. Cancer. 2012;118(13):3294–301. doi:10.1002/Cncr.26629.PubMedCrossRef

21.

Vazquez A, Khan MN, Blake DM, Sanghvi S, Baredes S, Eloy JA. Extranodal natural killer/T-Cell lymphoma: a population-based comparison of sinonasal and extranasal disease. Laryngoscope. 2014;124(4):888–95. doi:10.1002/lary.24371.PubMedCrossRef

22.

Sakata K, Fuwa N, Kodaira T, Aratani K, Ikeda H, Takagi M, et al. Analyses of dose-response in radiotherapy for patients with mature T/NK-cell lymphomas according to the WHO classification. Radiother Oncol. 2006;79(2):179–84. doi:10.1016/j.radonc.2006.03.014.PubMedCrossRef

23.

Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol. 1999;17(4):1244.PubMed

24.

Mraz-Gernhard S, Natkunam Y, Hoppe RT, LeBoit P, Kohler S, Kim YH. Natural killer/natural killer-like T-cell lymphoma, CD56+, presenting in the skin: an increasingly recognized entity with an aggressive course. J Clin Oncol. 2001;19(8):2179–88.PubMed

25.

Kim W, Song S-Y, Ahn Y, Ko Y-H, Baek C-H, Kim D, et al. CHOP followed by involved field radiation: is it optimal for localized nasal natural killer/T-cell lymphoma? Ann Oncol. 2001;12(3):349–52.PubMedCrossRef

26.

Lee J, Kim W, Park Y, Park S, Park K, Kang J, et al. Nasal-type NK/T cell lymphoma: clinical features and treatment outcome. Br J Cancer. 2005;92(7):1226–30.PubMedCentralPubMedCrossRef

27.

Sakamoto E, Yamane T, Nakane T, Takeoka Y, Hirose A, Hagihara K, et al. Temporary effective treatment with l-asparaginase for a patient with refractory nasal NK/T-cell lymphoma. Gan Kagaku Ryoho Cancer Chemother. 2005;32(12):1993–6.

28.

Nagafuji K, Fujisaki T, Arima F, Ohshima K. l-asparaginase induced durable remission of relapsed nasal NK/T-cell lymphoma after autologous peripheral blood stem cell transplantation. Int J Hematol. 2001;74(4):447–50.PubMedCrossRef

29.

Yong W, Zheng W, Zhu J, Zhang Y, Wei Y, Wang X, et al. Midline NK/T-cell lymphoma nasal-type: treatment outcome, the effect of l-asparaginase based regimen, and prognostic factors. Hematol Oncol. 2006;24(1):28–32.PubMedCrossRef

30.

Yamaguchi M, Suzuki R, Kwong YL, Kim WS, Hasegawa Y, Izutsu K, et al. Phase I study of dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. Cancer Sci. 2008;99(5):1016–20.PubMedCrossRef

31.

Daibata M, Bandobashi K, Kuroda M, Imai S, Miyoshi I, Taguchi H. Induction of lytic Epstein-Barr virus (EBV) infection by synergistic action of rituximab and dexamethasone renders EBV-positive lymphoma cells more susceptible to ganciclovir cytotoxicity in vitro and in vivo. J Virol. 2005;79(9):5875–9. doi:10.1128/jvi.79.9.5875-5879.2005.PubMedCentralPubMedCrossRef

32.

Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, et al. Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211. J Clin Oncol. 2009;27(33):5594–600.PubMedCrossRef

33.

Imashuku S, Kuriyama K, Teramura T, Ishii E, Kinugawa N, Kato M, et al. Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J Clin Oncol. 2001;19(10):2665–73.PubMed

34.

Takahashi N, Miura I, Chubachi A, Miura AB, Nakamura S. A clinicopathological study of 20 patients with T/natural killer (NK)-cell lymphoma-associated hemophagocytic syndrome with special reference to nasal and nasal-type NK/T-cell lymphoma. Int J Hematol. 2001;74(3):303–8. doi:10.1007/bf02982065.PubMedCrossRef

35.

Romero Fernandez E, Pardo JRP, Doyle A, Albendea MC, de la Rua AR. Hemophagocytic syndrome associated NK/T nasal type lymphoma presenting as hypereosinophilic syndrome: a case report and literature review. Leuk Res. 2011;35(7):E97–9. doi:10.1016/j.leukres.2010.12.020.PubMedCrossRef

36.

Chim C-S, Ma S-Y, Au W-Y, Choy C, Lie AK, Liang R, et al. Primary nasal natural killer cell lymphoma: long-term treatment outcome and relationship with the International Prognostic Index. Blood. 2004;103(1):216–21.PubMedCrossRef

37.

Suzuki R, Kimura H, Kwong Y-L, Maeda Y, Hashimoto C, Kim WS, et al. Pretreatment EBV-DNA copy number is predictive for response to SMILE chemotherapy for newly-diagnosed stage IV, relapsed or refractory extranodal NK/T-Cell lymphoma, nasal type: results of NKTSG phase II study. Blood. 2010;116(21):1183–4.

38.

Chan A, Tang T, Ng T, Shih V, Tay K, Tao M, et al. To SMILE or not: supportive care matters. J Clin Oncol. 2012;30(9):1015–6. doi:10.1200/JCO.2011.40.7098 author reply 6–7.PubMedCrossRef

39.

Hanakawa H, Orita Y, Sato Y, Takao S, Marunaka H, Morishita T, et al. Novel and simple prognostic index for nasal natural killer/T-cell lymphoma. Head Neck. 2014;36(4):551–6. doi:10.1002/hed.23322.PubMedCrossRef

Title: Trial of LVDP regimen (l-asparaginase, etoposide, dexamethasone, and cisplatin, followed by radiotherapy) as first-line treatment for newly diagnosed, stage III/IV extranodal natural killer/T cell lymphoma
Authors: Y. Q. Wang
Y. Yang
H. Y. Zhuo
L. Q. Zou
Y. Jiang
M. Jiang
Publication date: 01-02-2015
Publisher: Springer US
Published in: Medical Oncology / Issue 2/2015
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-014-0435-4

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Trial of LVDP regimen (l-asparaginase, etoposide, dexamethasone, and cisplatin, followed by radiotherapy) as first-line treatment for newly diagnosed, stage III/IV extranodal natural killer/T cell lymphoma

Abstract

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