Effective second-line chemotherapy for extranodal NK/T-cell lymphoma consisting of etoposide, ifosfamide, methotrexate, and prednisolone

Kim, Beom-Seok; Kim, Dong-Wan; Im, Seock‐Ah; Kim, Chul Woo; Kim, Tae-You; Yoon, Sung‐Soo; Heo, Dae Seog; Bang, Yung‐Jue; Park, S.; Kim, Byoung Kook; Kim, Noe Kyeong

doi:10.1093/annonc/mdn551

Cited by 38 publications

(28 citation statements)

References 34 publications

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“…11 The complete response rate to conventional chemotherapy in patients with stage III or IV disease is less than 15%, 24,25 whereas 6 of our 7 patients with stage IV disease responded, with 4 of them entering complete remission (50%). These results, obtained in a prospective trial, confirm those obtained by the Chinese group who first reported the use of asparaginase to treat NK/T-cell lymphoma, in 4 retrospective series.…”

Section: Discussionmentioning

confidence: 71%

“…Chemotherapy protocols used for lymphomas of other histologic subtypes are poorly effective, at least in part, because of frequent multidrug resistance gene expression by tumor cells. 9 Patients with disseminated or relapsing disease have a very poor outcome, 4,10,11 and there is no standard management for relapsed or refractory disease. We and others, in small retrospective studies, [12][13][14][15][16] have observed very good response and survival rates in patients treated with L-asparaginase, a drug with an original antitumoral mechanism not affected by MDR.…”

Section: Introductionmentioning

confidence: 99%

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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

Jaccard

Gachard

Marin³

et al. 2011

Blood

334

266

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IntroductionExtranodal natural killer (NK)/T-cell lymphoma, nasal type, is a rare and severe malignancy. It is more frequent in Asia and Central/South America than in Europe and North America. It is thought to arise from NK cells or, occasionally, from a subset of ␥␦ or ␣␤ cytotoxic T cells, and shows a tight association with Epstein-Barr virus (EBV). It is classically characterized by a cytoplasmic CD3 ⑀ phenotype, with no surface CD3 or T-cell receptor expression, no T-cell receptor gene rearrangements, an activated cytotoxic profile with perforin, granzyme B, and TIA-1 expression, and frequent CD56 expression. [1][2][3] Extranodal NK/T-cell lymphoma is usually diagnosed in adults, with a median age in the fifth decade. The nasal cavity or other parts of the upper aerodigestive tract are primarily involved, but some cases occur at extranasal sites. The term "nasal-type" is used in the World Health Organization classification to describe forms arising both in the nasal cavity and in extranasal sites. 3,4 Because disease incidence is rare even in prevalent areas, there has been no randomized controlled trial, and most treatment protocols are consensus-guided. 5 Localized NK/T-cell lymphomas often respond to radiotherapy 6,7 or to concurrent radiation and chemotherapy, 8 but relapse is common. Chemotherapy protocols used for lymphomas of other histologic subtypes are poorly effective, at least in part, because of frequent multidrug resistance gene expression by tumor cells. 9 Patients with disseminated or relapsing disease have a very poor outcome, 4,10,11 and there is no standard management for relapsed or refractory disease. We and others, in small retrospective studies, 12-16 have observed very good response and survival rates in patients treated with L-asparaginase, a drug with an original antitumoral mechanism not affected by MDR. NK cells lack asparagine synthase activity, and asparaginase has been shown to induce apoptosis of tumoral NK cells in vitro. 17 These findings provided the rationale for this open-label phase 2 study of an L-asparaginase-containing regimen for patients with relapsed and/or refractory extranodal NK/T-cell lymphoma. We chose to combine L-asparaginase with methotrexate, a drug insensitive to the multidrug resistance pathway, because of its well-known synergistic effect with asparaginase in acute lymphoblastic leukemia and its ability to prevent central nervous system involvement. Dexamethasone was added because T-cell lymphomas are usually sensitive to corticosteroids and dexamethasone For personal use only. on May 12, 2018. by guest www.bloodjournal.org From seems to be associated with a lower risk of thrombosis when given with L-asparaginase. 18 Methods PatientsThe patients were at least 18 years of age, with relapsed or refractory extranodal NK/T-cell lymphoma. Eligibility criteria included biopsyproven diagnosis of NK/T-cell lymphoma, nasal-type, irrespective of the anatomic site. Malignant cells in all cases had a CD3⑀ ϩ , CD20 Ϫ phenotype, a cytotoxic profile, and evidence of E...

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

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

Jaccard

Gachard

Marin³

et al. 2011

Blood

334

266

View full text Add to dashboard Cite

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“…More recently, the results of a single-institution but well-designed prospective phase II study were published [53]. In this study, 32 patients with relapsed or refractory ENKL were treated with IMVP-16/Pd (ifosfamide, methotrexate, etoposide, and prednisolone) therapy as a secondline chemotherapy from October 1996 to February 2002.…”

Section: Clinical Trials In the Early 2000smentioning

confidence: 99%

Current and future management of NK/T-cell lymphoma based on clinical trials

Yamaguchi

2012

Int J Hematol

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Recently reported results of well-designed prospective clinical trials for extranodal NK/T-cell lymphoma, nasal type (ENKL) have rapidly changed the management of ENKL. This review will focus on the evidence obtained from prospective clinical trials for ENKL and discuss the most highly recommended current management and future directions for the better management of ENKL. For patients with nasal NK/T-cell lymphoma of stage IE or contiguous stage IIE with cervical node involvement, concurrent chemoradiotherapy with radiotherapy (RT) and a two-thirds dose of DeVIC chemotherapy is recommended as a first-line treatment. To obtain the expected clinical outcome, performing RT following the same procedure as that reported is important. For the other patients with newly diagnosed ENKL, SMILE chemotherapy is recommended as an induction therapy. The Epstein-Barr virus DNA load in peripheral blood is useful for both prognostication and monitoring during the follow-up after treatment. Other L-asparaginasecontaining chemotherapies and chemotherapies containing non-multidrug resistance-related agents and etoposide are good options for elderly patients or patients with impaired organ function. As in the cases of other aggressive lymphomas, prospective clinical trials with adequate statistical considerations should be conducted to improve the prognosis of patients with ENKL.

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“…Chemotherapy may yield more benefits by reducing the risk of distant metastasis. However, anthracycline-based chemotherapy regimens (e.g., cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]) have shown disappointing efficacy for NKTCL, partially due to the overexpression of a multidrug-resistant gene in NKTCL cells [7][8][9]. Novel regimens containing Lasparaginase (L-ASP) or pegaspargase have elicited promising responses [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Radiotherapy and PGEMOX/GELOX regimen improved prognosis in elderly patients with early-stage extranodal NK/T-cell lymphoma

Xia

Zhang

et al. 2015

Ann Hematol

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The optimal treatment strategy for elderly patients with natural killer/T-cell lymphoma (NKTCL) remains to be established. A total of 63 elderly patients with newly diagnosed NKTCL were retrospectively reviewed. Among the patients with stage I-II disease, 58.3 % received radiotherapy (RT) ± chemotherapy, and 41.7 % received chemotherapy alone. Compared with chemotherapy alone, RT ± chemotherapy elicited a significantly higher overall response rate (ORR) (100 vs. 57.1 %, P < 0.001) and substantially prolonged 5-year overall survival (OS) (55.3 vs. 18.0 %, P < 0.001) in patients with stage I-II disease. Compared with other chemotherapeutic regimens, pegaspargase plus gemcitabine and oxaliplatin (PGEMOX)/L-asparaginase plus gemcitabine and oxaliplatin (GELOX) was associated with a significantly higher ORR (92.9 vs. 51.6 %, P = 0.009) and a significantly improved 5-year OS (78.6 vs. 23.9 %, P = 0.010) in patients with stage I-II disease. Nine patients with stage I-II disease who were treated with PGEMOX/GELOX followed by RT had an encouraging outcome (5-year OS 100 %, 5-year progression-free survival (PFS) 85.7 %), which was superior to that of patients receiving other regimens followed by RT. In conclusion, RT played an important role for elderly patients with early-stage NKTCL, and the PGEMOX/GELOX regimen was superior to other regimens. The combination of them may be a promising treatment option.

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Effective second-line chemotherapy for extranodal NK/T-cell lymphoma consisting of etoposide, ifosfamide, methotrexate, and prednisolone

Abstract: This chemotherapy regimen was moderately effective for relapsed/refractory extranodal NTCL, nasal type. Toxic effects were moderate, but caution should be exercised to prevent severe infection.

Cited by 38 publications

References 34 publications

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

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

Current and future management of NK/T-cell lymphoma based on clinical trials

Radiotherapy and PGEMOX/GELOX regimen improved prognosis in elderly patients with early-stage extranodal NK/T-cell lymphoma

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