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

Abstract

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal-type, is a distinct entity of lymphoid tissue. ENKTL is sensitive to radiotherapy (RT), but the prognosis is poorer than for other types of early lymphoma. The treatment schedule is controversial. METHODS: A phase 2 study was conducted of ''sandwich'' protocols, with earlier RT after an initial 2 to 3 cycles of LVP (L-asparaginase, vincristine, and prednisone), followed by further ''consolidation'' cycles. Patients aged 18 years and older who had previously untreated ENKTL and localized lesions in the upper aerodigestive tract were enrolled. The primary endpoints were objective response rate and complete remission rate. The secondary endpoints were 2-year overall survival, 2-year progression-free survival, and toxicity. This study is registered with www.Chictr.org, number ChicTR-TNC-00000394, and is ongoing for long-term follow-up. RESULTS: Twenty-six patients completed total therapy, which resulted in 88.5% response that included 21 patients (80.8%) with complete response (CR) and 2 patients (7.7%) with partial response. Three (11.5%) of 26 patients progressed during therapy. With a median follow-up of 27 months (range, 4-35 months), the 2-year overall survival was 88.5%, and the 2-year progression-free survival was 80.6%. Patients with CR had better prognosis than patients without CR. Only 2 patients (7.7%) experienced grade 3 leukocytopenia. No grade 4 toxicity or treatment-related deaths were observed. CONCLUSIONS: The research showed that the ''sandwich'' protocol of LVP combined with RT was a safe and effective treatment for localized nasal natural killer/T-cell lymphoma, and the results warrant further investigation into this protocol. Cancer 2012;118:3294-

"Sandwich" Chemotherapy (CT) with Radiotherapy (RT) Improves Outcomes in Patients with Stage IE/IIEExtranodal Natural Killer (NK)/T-cell Lymphomas

“…Compared with RT alone, whether initial CT followed by RT can improve the CR rate is controversial. It fluctuates from 74.1% to 81% for this type of CMT (Li et al, 2006;Jiang et al, 2012;Wang et al, 2013), which can be comparable to the result (77%~84.6%) for CCRT (Kim et al, 2009;Yamaguchi et al, 2009;Lee et al, 2011). However, the CR rate (66%) was lower for the initial CT followed by RT than that (69%) for RT alone (Kim et al, 2001a), and the RT alone group appeared to have the highest CR rate (97%) (Li et al, 2006).…”

“…The CR rate of initial CT for localized ENKTL varies greatly from 20% to 56% (Kim et al, 2001b;Li et al, 2006;Huang et al, 2008;Jiang et al, 2012;Kwong et al, 2012;Wang et al, 2013). In these studies, the CR rates are no more than 40% for the anthracycline-containing CT, but they are beyond 42% when non-anthracycline schedules are used, such as SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide), GELOX, and LVP (L-asparaginase, vincristine, and prednisone).…”

“…Recently, two phase II trials from Japan and Korea have showed excellent survival outcomes of concurrent chemoradiotherapy (CCRT) for localized ENKTL (Kim et al, 2009;Yamaguchi et al, 2012). Another phase II trial indicates the "sandwich" protocol of combined CT with RT is a safe and effective treatment in this setting (Jiang et al, 2012). However, CMT was not accompanied by an improvement on survival in a lot of studies (Shikama et al, 1997;Kim et al, 2001b;Li et al, 2006;Ma et al, 2010).…”

New Therapies in T-cell Lymphoma

“…The l-asparaginase, vincristine, and prednisolone (LVP) regimen for six cycles with radiotherapy dovetailed between cycle two and three displayed an overall response rate of 89%, complete response rate of 81%, and an impressive two-year OS of 88.5% and progressive free survival of 80.6%. 67 Similar impressive phase II data was displayed using gemcitabine, l-asparaginase, and oxaliplatin (GELOX) followed by involved-field radiotherapy (56 Gy) for patients with stage IE/IIE Extranodal NK/T-cell lymphoma. 68 The overall response rate was 96% and complete response rate was 74%, and two-year OS and progressive free survival were both 86% in the 27 patients treated.…”

A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T‐cell lymphoma, nasal type: a multicenter trial in Northwest China

“…Three studies using simultaneous chemoradiotherapy42, 43, 44, 45 and 3 assessing chemotherapy followed by RT46, 47, 48 had ORRs of 78% to 96%, 2‐year OS rates of 78% to 88%, and 3‐year OS rates of 54% to 86%. The newly diagnosed patients in our study had an ORR of 88% and a 2‐year OS rate of 84%.…”