scholarly journals Final Report on Phase II Trial of L-Asparaginase Plus Concurrent Chemoradiotherapy Followed By Midle (Methotrexate, Ifosfamide, Etoposide, Dexamethasone, and L-asparaginase) Chemotherapy for Patients with Newly Diagnosed Stage I/II Extranodal NK/T-Cell Lymphoma, Nasal Type

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3942-3942
Author(s):  
Dok Hyun Yoon ◽  
Seok Jin Kim ◽  
Seong Hyun Jeong ◽  
Dong-Yeop Shin ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
T Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Nasal Type ◽  
Nk T Cell ◽  
Grade 3

Abstract Background We previously have shown that concurrent chemoradiotherapy (CCRT) followed by chemotherapy such as VIPD (etoposide, ifosfamide, cisplatin and dexamethasone) or VIDL (etoposide, ifosfamide, dexamethasone and L-asparaginase) is an effective treatment for the management of localized extranodal NK/T-cell lymphoma (ENKTL), nasal type. To further improve efficacy, we designed a new treatment protocol, MIDLE (methotrexate, ifosfamide, dexamethasone, L-asparaginase and etoposide), which incorporates tri-weekly administration of L-asparaginase during CCRT to reduce the probability of systemic progression and high dose methotrexate to intensify chemotherapy based on previous excellent outcomes of methotrexate-containing regimens such as SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) and MLD (methotrexate, L-asparaginase, dexamethasone). Methods The treatment scheme of CCRT consisted of radiation 36-45 Gy and weekly administration of cisplatin 30 mg/m2 (total: 4 doses). During the CCRT, tri-weekly 4,000 IU of Escherichia coli L-asparaginase was administered intravenously (IV). The chemotherapy, MIDLE (methotrexate 3 g/m2 on day 1, etoposide 100 mg/m2, Ifosfamide 1000 mg/m2 on day 2-3, dexamethasone 40mg on day 1-4, and L-asparaginase 6000 IU/m2 IV on day 4, 6, 8, 10) was repeated every 28 days for two cycles. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov(NCT01238159). Results Twenty-eight patients with stage IE/IIE ENKTL were enrolled, and the median age was 51 years (range, 30-77 years). Twenty four patients were male while only four patients were female. Twenty-two patients had stage IE and six IIE disease. Twenty four were classified as low risk group and the other four intermediate group according to PINK-E (Kim SJ et al., EHA 2015 S110). All but two patients completed CCRT, which resulted in 85.7% of overall response rate including 16 complete responses (57.1%) and 8 partial responses (28.6%). One showed stable disease (SD) and the other one showed progressive disease (PD) with development of new distant lymph node involvement after CCRT. Grade 3 or 4 hematologic toxicity was not common. Only two patients experienced G3 neutropenia during or after CCRT. However, grade 3 non-hematologic toxicities were noted including bilirubin elevation (n = 3), mucositis (n = 1), anorexia (n=5) and nausea/vomiting (n = 11) Two could not complete CCRT according to the protocol due to G3 allergic reaction to L-asparaginase (n=1) and prolonged G3 mucositis (n=1). After the completion of CCRT, 23 out of 28 patients entered the MIDLE chemotherapy as five patients including one disease progression and four withdrawal during (n=2) or after (n=2) CCRT due to toxicities. All those who completed the planned two cycles of MIDLE chemotherapy achieved complete response after chemotherapy including those with PR (n=6) and SD (n=1) after CCRT. Three patients dropped out during or after their first cycle of MIDLE due to non-hematologic toxicities (recurrent G3 bilirubinemia (n=1), G3 increased creatinine (n=1), G5 infection (n=1)). The final complete response rate was 82% (23/28). It was associated with a significant rate of grade 3/4 neutropenia (n=21) and febrile neutropenia (n=10). Two patients experienced acute kidney injury (AKI) during the first cycle of MIDLE and one of them died of pneumonia complicated by sepsis. With a median follow-up of 46 months (95% confidence interval: 39 - 47 months), four patients progressed and five patients died with the estimated 3-year progression-free survival rate of 74.1% and overall survival rate of 81.5%. PINK-E could successfully stratify both time-to-progression (p=003) and overall survival (p=0.006) in this study. Conclusion L-asparaginase plus concurrent chemoradiotherapy followed by MIDLE chemotherapy may be an effective treatment strategy for stage I/II extranodal NK/T-Cell lymphoma, nasal type. However, higher numbers of patients were withdrawn during or after CCRT due to toxicity or poor tolerance than previous study. MIDLE chemotherapy was associated with high rate of G3 or 4 hematologic toxicities. Thus, this approach should be reserved for selected patients such as young fit but high risk of relapse. PINK-E can be a useful prognostic index for stage I/II extranodal NK/T-Cell lymphoma, nasal type. Disclosures No relevant conflicts of interest to declare.

Phase II Trial Of L-Asparaginase Plus Concurrent Chemoradiotherapy Followed By Midle (methotrexate, ifosfamide, etoposide, dexamethasone, and L-asparaginase) Chemotherapy For Patients With Newly Diagnosed Stage I/II Extranodal NK/T-Cell Lymphoma, Nasal Type

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3037-3037 ◽  
Author(s):  
Seok Jin Kim ◽  
Dok Hyun Yoon ◽  
Seong Hyun Jeong ◽  
Dong-Yeop Shin ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
T Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Nasal Type ◽  
Nk T Cell ◽  
Grade 3

Abstract Background The treatment of localized extranodal NK/T-cell lymphoma (ENKTL), nasal type has shifted to non-anthracycline-based intensive chemotherapy with radiotherapy since the poor response of ENKTL to anthracycline due to the expression of a multidrug-resistant (MDR) p-glycoprotein was proven. We previously proposed concurrent chemoradiotherapy (CCRT) followed by chemotherapy which is not affected by MDR and reported a significant improvement of outcomes of localized ENKTL. Based on our accumulated data, we designed a new treatment protocol. First, we added tri-weekly administration of L-asparaginase to reduce the probability of systemic progression during CCRT. Second, we designed MIDLE (methotrexate, ifosfamide, etoposide, dexamethasone, and L-asparaginase) according to previous excellent outcomes of methotrexate-containing regimens such as SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) and MLD (methotrexate, L-asparaginase, dexamethasone). Methods The treatment scheme of CCRT consisted of radiation 40 Gy and weekly administration of cisplatin 30 mg/m2 (total: 4 doses). During the CCRT, tri-weekly intravenous (IV) administration of 4,000 IU of Escherichia coli L-asparaginase was done. The chemotherapy, MIDLE (methotrexate 3g/m2 on day 1, etoposide 100mg/m2, Ifosfamide 1000mg/m2 on day 2-3, dexamethasone 40mg on day 1-4, and L-asparaginase 6000IU/m2 IV on day 4, 6, 8, 10) was repeated every 28 days up to 2 cycles. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov(NCT01238159). Results Twenty-eight patients with stage IE/IIE ENKTL were enrolled, and the median age was 51 years (range, 30–77 years). 24 patients were male while only four patients were female. Twenty-two patients were stage IE and six were IIE. All patients completed CCRT, which resulted in 92.9% of overall response rate including 20 complete responses and 6 partial responses. One patient showed stable disease after CCRT whereas the other patient progressed. No grade 3 or 4 hematologic toxicity was found during CCRT. However, grade 3 non-hematologic toxicities included bilirubin elevation (n = 4), mucositis (n = 1), and nausea/vomiting (n = 6). After the completion of CCRT, 23 patients entered the MIDLE chemotherapy as five patients including one disease progression and four cases of withdrawal could not receive MIDLE. All patients achieved complete response after they completed the planned two cycles of MIDLE chemotherapy whereas two patients dropped out after their first cycle due to non-hematologic toxicity. The final complete response rate of patients enrolled was 92.9% (26/28). The major toxicity of MIDLE was grade 3/4 leucopenia, and the non-hematologic toxicity included mucositis and nausea/vomiting. The hepatic toxicity-associated with L-asparaginase was frequent. However, the majority of the hepatic toxicities were grade 1 or 2. With the median potential follow-up of 25 months (95% confidence interval: 19 – 31 months), four patients relapsed. Conclusion L-asparaginase plus concurrent chemoradiotherapy followed by MIDLE chemotherapy can be an effective treatment strategy with acceptable toxicity in stage I/II extranodal NK/T-Cell lymphoma, nasal type. Disclosures: Kwak: celgene: Research Funding.

Preliminary Results Of Treatment Extranodal NK/T-Cell Lymphoma, Nasal Type Stage I-II AT K Hospital

2020 ◽  
Author(s):  
Linh Phan Van
Keyword(s):  
T Cell ◽  
Partial Response ◽  
Concurrent Chemoradiotherapy ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Female Ratio ◽  
Nasal Type ◽  
Results Of Treatment ◽  
Nk T Cell

Background: Extranodal NK/T-cell lymphoma, nasal type, is a rare subtype of non-Hodgkin lymphoma, origin from natural killer (NK) cells and T cells. This is a rare, fast-growing and poor prognosis disease. Currently there have been not many studies in Vietnam on this issue. We conduct this research with two objects: to describe characteristics of patients and evaluate premininary results of treatment extranodal NK/T cell lymphoma, nasal type, stage I to II at K hospital. Methods: Retrospective study. From January 2017 to June 2020, we enrolled 26 patients with extranodal NK/T cell lymphoma, nasal type, stage I to II. Patients were treated concurrent chemoradiotherapy with cisplatin, followed by 3 cycles of VIPD adjuvant regimen. Results: Patient characteristics: The average age was 43.2. Male/female ratio was 1.36. The most common symptoms were stuffy of nose 84.6%; runny nose 65.4%. Peripheral lymph nodes observed in 19.2%; 50% with B symptom. Staged I was dominated with 73.1%. Treatment results: Concurrent chemoradiotherapy phase: completed response was 26.9%, partial response 53.8% and progression disease 19.2%. At the end of treatment course, the overall response rate was 73% (including 61.5% completed response and 11.5% partial response), 26.9% cases with disease progression. Toxicity: Leukopenia was the most common toxicity (61.1%). Grade III and IV leukopenia were observed in 18.4%. Conclusions: Concurrent chemoradiotherapy followed by adjuvant VIPD regimen with stage I, II is effective regimen and acceptable toxicity.

scholarly journals Phase II trial of concurrent chemoradiotherapy with L-asparaginase and MIDLE chemotherapy for newly diagnosed stage I/II extranodal NK/T-cell lymphoma, nasal type (CISL-1008)

Oncotarget ◽  
2016 ◽  
Vol 7 (51) ◽  
pp. 85584-85591 ◽  
Author(s):  
Dok Hyun Yoon ◽  
Seok Jin Kim ◽  
Seong Hyun Jeong ◽  
Dong-Yeop Shin ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Concurrent Chemoradiotherapy ◽  
Phase Ii Trial ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Newly Diagnosed ◽  
Nasal Type ◽  
Nk T Cell

Concurrent Chemo-Radiotherapy Followed by VIDL (Etoposide, Ifosfamide, Dexamethasone, L-asparaginase) Chemotherapy In Stage I/II Extranodal NK/T-Cell Lymphoma of Nasal Cavity/Nasopharynx

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1765-1765
Author(s):  
Seok Jin Kim ◽  
Hyeon-Seok Eom ◽  
Jin Seok Kim ◽  
Jae-Yong Kwak ◽  
Deok-Hwan Yang ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Major Toxicity ◽  
Nk T Cell ◽  
Grade 3

Abstract Abstract 1765 Background Localized extranodal NK/T-cell lymphoma (ENKTL) mainly occurs in nasal and/or nasopharynx. Thus, ENKTL shows a poor response to anthracycline-based chemotherapy because of the frequent expression of a multidrug-resistant p-glycoprotein, radiotherapy for localized disease produces a higher complete response rate than chemotherapy. However, when ENKTL is treated with radiation alone, local and systemic failures are frequently observed. Therefore, our group previously reported the improved outcome of concurrent chemo-radiotherapy (CCRT) with weekly administration of cisplatin followed by systemic chemotherapy VIPD (etoposide, ifosfamide, cisplatin and dexamethasone). However, the grade 3/4 hematologic toxicity was the major toxicity of VIPD. Thus, in consideration of the risk of toxicity of VIPD, we designed VIDL (etoposide, ifosfamide, dexamethasone, and L-asparaginase) as adjuvant to CCRT. Because etoposide and ifosfamide are less affected by p-glycoprotein, and NK lymphoma cells are known as being sensitive to L-asparaginase, we expected VIDL regimen could be more effective and less toxic than VIPD. Methods Thirty-one newly diagnosed stage IE/IIE nasal/nasopharynx ENKTL patients received CCRT (radiation 40–50.4 Gy and cisplatin 30 mg/m2 weekly). Two cycles of VIDL (etoposide 100 mg/m2 D1–D3, ifosfamide 1200 mg/m2 D1–D3, dexamethasone 40 mg D1–D3, and L-asparaginase 4000IU/m2) were scheduled after CCRT. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov (NCT01007526). Results The median age was 46.5 years (range, 22–71 years); 78.1% of all patients were younger than 60 years of age, and male (n = 21) to female (n = 11) was 2:1. Twenty-two patients were stage IE and nine were IIE. The majority of patients were in the low (n = 24) or low–intermediate (n = 6) risk categories of the International Prognostic Index. However, when we grouped patients based on the NK/T cell lymphoma prognostic index (NKPI) proposed previously for ENKTL, which includes the presence of B cell symptoms, lesions at stage III or IV, elevated serum LDH concentration, and lymph node involvement, 25 patients belonged to group I or II and 7 patients were group III or IV (those with more than two risk factors). All patients completed CCRT, which resulted in 90.3% overall response rate including 22 complete response (CR) and 6 partial response (PR). Twenty-seven patients completed the planned two cycles of VIDL while four patients did not because three patients progressed during or after CCRT, and one patient is ongoing. The overall response rate of 27 patients completed VIDL was 92.6%, and two patients relapsed after the completion of VIDL chemotherapy. The major toxicity of VIDL was grade 3/4 leucopenia (85.1%), but there was no treatment-related mortality. The non-hematologic toxicity was tolerable, and the hepatic toxicity-associated with the use of L-asparaginase was frequent (55.5%). However, the majority of the hepatic toxicities were grade 1 or 2. Conclusion Concurrent chemo-radiotherapy followed by VIDL chemotherapy can be an effective treatment strategy with acceptable toxicity in stage I/II extranodal NK/T-Cell lymphoma of nasal cavity/nasopharynx. Disclosures: No relevant conflicts of interest to declare.

Primary radiotherapy showed favorable outcome in treating extranodal nasal-type NK/T-cell lymphoma in children and adolescents

Blood ◽  
2009 ◽  
Vol 114 (23) ◽  
pp. 4771-4776 ◽  
Author(s):  
Zhao-Yang Wang ◽  
Ye-Xiong Li ◽  
Wei-Hu Wang ◽  
Jing Jin ◽  
Hua Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Children And Adolescents ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Early Stage ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Nasal Type ◽  
Primary Radiotherapy ◽  
Nk T Cell

Abstract Extranodal nasal-type natural killer (NK)/T-cell lymphoma is rarely observed in children and adolescents. We aim to investigate the clinical features, prognosis, and treatment outcomes in these patients. Thirty-seven patients were reviewed. There were 19, 14, 2, and 2 patients with stage I, stage II, stage III, and stage IV diseases, respectively. Among the patients with stage I and II disease, 19 patients received initial radiotherapy with or without chemotherapy, and 14 patients received chemotherapy followed by radiotherapy. The 4 patients with stage III and IV disease received primary chemotherapy and radiation of the primary tumor. Children and adolescents with extranodal nasal-type NK/T-cell lymphoma usually presented with early-stage disease, high frequency of B symptoms, good performance, low-risk age-adjusted international prognostic index, and chemoresistance. The complete response rate after initial radiotherapy was 73.7%, which was significantly higher than the response rate after initial chemotherapy (16.7%; P = .002). The 5-year overall survival (OS) and progression-free survival (PFS) rates for all the patients were 77.0% and 68.5%, respectively. The corresponding OS and PFS rates for patients with stage I and II disease were 77.6% and 72.3%, respectively. Children and adolescents with early-stage extranodal nasal-type NK/T-cell lymphoma treated with primary radiotherapy had a favorable prognosis.

Radiotherapy Alone With Curative Intent in Patients With Stage I Extranodal Nasal-Type NK/T-Cell Lymphoma

2012 ◽  
Vol 82 (5) ◽  
pp. 1809-1815 ◽  
Author(s):  
Ye-Xiong Li ◽  
Hua Wang ◽  
Jing Jin ◽  
Wei-Hu Wang ◽  
Qing-Feng Liu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Curative Intent ◽  
Nasal Type ◽  
Radiotherapy Alone ◽  
Nk T Cell

The Efficacy of Bortezomib-CHOP In Patients with Advanced Stage T or NK/T Cell Lymphomas: The Results of Multicenter Phase II Study.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1791-1791 ◽  
Author(s):  
Seok Jin Kim ◽  
Hyeon-Seok Eom ◽  
Jin Seok Kim ◽  
Hye Jin Kang ◽  
Hyo Jung Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Advanced Stage ◽  
Chop Regimen ◽  
T Cell Lymphomas ◽  
Nk T Cell

Abstract Abstract 1791 Background Advanced stage T-cell or NK/T-cell lymphomas usually show aggressive clinical course and their treatment outcomes are worse than B-cell non-Hodgkin lymphoma. Furthermore, the optimal treatment regimen is not still established for these disease entities. At present, cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen is still used as a primary treatment for advanced stage T or NK/T cell lymphomas although its efficacy is not satisfactory. Thus, more effective treatment regimen is required to improve treatment outcome. The incorporation of new targeted agents into CHOP regimen has been a widely used strategy to develop new regimen for the treatment of lymphoma. Bortezomib, a proteasome inhibitor approved for the use of treatment of multiple myeloma has been tried in many B-cell non-Hodgkin lymphomas. A recent in vitro study results showed that proteasome inhibitor could inhibit the growth of NK/T lymphoma cells. Based on these results, we designed a regimen combining CHOP with. Our previous phase I study determined the maximum tolerated dose of bortezomib as 1.6mg/m2 for combination with CHOP. Thus, we performed the phase II study to evaluate the efficacy of bortezomib plus CHOP chemotherapy. Methods We enrolled patients with newly diagnosed T or NK/T cell lymphoma. All patients were Ann Arbor stage III/IV and had adequate organ function. Patients received bortezomib on days 1 and 8 (weekly schedule, 1.6 mg/m2 per dose) in addition to 750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, 1.4 mg/m2 vincristine on day 1 and 100 mg/day prednisolone on days 1 to 5, every 3 weeks. Six cycles of therapy administered every 21 days were planned. All patients provided written informed consents and this trial was registered at www.ClinicalTrials.gov (NCT00374699). Results 46 patients were enrolled between April 2007 and August 2009. Peripheral T-cell lymphoma, unspecified (n=16) and extranodal NK/T cell lymphoma (n=10) were dominant subtypes while angioimmunoblastic T-cell lymphoma (n=8) and ALK-negative anaplastic large cell lymphoma (n=6) account for 30.4% of all patients. Five patients with cutaneous T-cell lymphoma and one hepatosplenic T-cell lymphoma were also recruited. The median age at diagnosis was 52 years (range 21 – 66 years). Serum LDH elevation (n = 28, 60.9%) and stage IV patients were dominant (n = 32, 69.6%). Thus, the International Prognostic Index risk was dominantly high or high-intermediate (n = 26, 56.5%). Complete response was achieved in 30 patients (65.2%) and partial response was 5 patients (10.9%). As a result, the overall response rate was 76.1%. The comparison of complete response rate based on the subtype demonstrated that the complete response rate of peripheral T-cell lymphoma, unspecified (12/19, 63.2%), angioimmunoblastic T-cell lymphoma (6/8, 75%), anaplastic large cell lymphoma (4/6, 66.7%) and cutaneous T-cell lymphoma (5/5, 100.0%) was better than extranodal NK/T cell lymphoma (3/10, 30.0%). Five patients with extranodal NK/T cell lymphoma progressed during the treatment with bortezomib and CHOP. The hematologic toxicity was the major toxicity of this regimen, thus, grade 3/4 leucopenia and febrile neutropenia were the most frequent toxicity. However, there was no treatment-related mortality. In addition, neurotoxicity was tolerable, so the majority of peripheral neurotoxicity was grade 1 or 2. Conclusion The combined treatment of bortezomib with CHOP is an effective regimen for advanced stage T-cell lymphomas with acceptable toxicity. However, it may not be efficient for advanced stage extranodal NK/T-cell lymphomas. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Ki-67 expression is predictive of prognosis in patients with stage I/II extranodal NK/T-cell lymphoma, nasal type

2007 ◽  
Vol 18 (8) ◽  
pp. 1382-1387 ◽  
Author(s):  
S.J. Kim ◽  
B.S. Kim ◽  
C.W. Choi ◽  
J Choi ◽  
I Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Ki 67 ◽  
Nasal Type ◽  
Nk T Cell

Phase I/II Study of Concurrent Chemoradiotherapy for Newly-Diagnosed, Localized Nasal NK/T-Cell Lymphoma: Results of a Phase I Portion of JCOG0211-DI.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2685-2685 ◽  
Author(s):  
Motoko Yamaguchi ◽  
Masahiko Oguchi ◽  
Kensei Tobinai ◽  
Nobuo Maseki ◽  
Takayo Suzuki ◽  
...  
Keyword(s):  
T Cell ◽  
Phase I ◽  
Concurrent Chemoradiotherapy ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Newly Diagnosed ◽  
Level 1 ◽  
Nk T Cell ◽  
Grade 3 ◽  
Level 2

Abstract Nasal NK/T-cell lymphoma is a rare lymphoid neoplasm, and its standard therapy has not been established. It is one of the Epstein-Barr virus (EBV) - associated lymphoid malignancies, and lymphoma cells express P-glycoprotein concerning multi-drug resistance (MDR) of the disease. Anthracycline-containing chemotherapy followed by radiotherapy (RT) has been established as the standard care for localized aggressive NHL; however this strategy is not effective for localized nasal NK/T-cell lymphoma. The 5-year overall survival rates of RT alone are only 30–40%. To explore a more effective treatment for newly-diagnosed localized nasal NK/T-cell lymphoma, we conducted a multicenter phase I/II study of concurrent chemoradiotherapy consisted of 50 Gy of RT and 3 courses of DeVIC chemotherapy [carboplatin (CBDCA) 300mg/m2 d1 IV, etoposide (ETP) 100mg/m2 d1-3 IV, ifosfamide (IFM) 1.5g/m2 d1-3 IV, dexamethasone (DMS) 40mg/body d1-3 IV; every 21 days]. DeVIC comprised of MDR-non-related agents and ETP that shows both in vitro and in vivo efficacy for NK-cell neoplasms, and is well-known to be effective for EBV-associated hemophagocytic syndrome. Pts with newlydiagnosed, localized (IE and contiguous IIE with cervical node involvement) diseases, 20–69 years of age and PS 0–2 were eligible. The protocol requests the CT based 2 or 3 dimensional RT planning that the volume with appropriate margin (2 cm) to gross tumor, entire nasal cavities and nasopharynx should be irradiated. In the phase I portion, a standard 3+3 design was used to evaluate dose-limiting toxicities (DLTs). The doses of RT and DMS were fixed. Two dose levels of CBDCA/ETP/IFM were evaluated: Level 1 (2/3-dose DeVIC) CBDCA 200mg/m2, ETP 67mg/m2, IFM 1.0g/m2 and Level 2 (100%-dose DeVIC). Enrolled 10 pts showed the following features: age 30–61 yrs (median 44.5), M:F=5:5, stage IE 6, stage IIE 4, B symptom(+) 4, elevated serum LDH 2, PS0 6, PS1 4. No treatment-related death occurred, and no grade 4 non-hematologic toxicities other than transient hypokalemia were observed. Grade 4 neutropenia and grade 3 mucositis due to RT were common. At Level 2, grade 4 leukopenia/anemia/thrombocytopenia and grade 3 infection were more frequent than Level 1. In summary, at Level 1, 1 pt developed PD before evaluation of DLT. Remaining 3 pts did not develop DLT. At Level 2, 4 out of 6 pts developed DLT. Thus, we decided to select the Level 1 for the subsequent phase II portion. Of all 10 enrolled pts, 7 achieved CR, 2 PD, and 1 not evaluable. Of note, all 10 pts achieved local control. Our results suggest that concurrent chemoradiotherapy using MDR-non-related agents and ETP is a promising treatment strategy for localized nasal NK/T-cell lymphoma. Feasibility and efficacy of Level 1 will be evaluated further in the phase II portion.

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