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

Abstract

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/m(2) of cisplatin for 4 weeks. Two cycles of VIDL (etoposide (100 mg/m(2)), ifosfamide (1,200 mg/m(2)), and dexamethasone (40 mg) from days 1 to 3, and L-asparaginase (4,000 IU/m(2)) 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.

Risk-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma: analysis from a multicenter study

“…To avoid a delay in RT, several prospective trials applied concurrent chemoradiotherapy, with reported 5-year OS rates of 60% to 73%. [37][38][39][40] In this large cohort of early-stage patients, the 5-year OS rates after RT alone for the low-risk group (88.8%) or after sequential RT and CT for the high-risk group (72.2%) were superior or comparable to other recent small series of concurrent, sequential, or "sandwich" CT and RT, regardless of the CT regimen. [36][37][38][39][40][41][42][43][44] Therefore, RT followed by optional CT offers the advantage of effective RT and has a more tolerable safety profile [4][5][6]15,16 and may reduce the risk of chemoresistance.…”

Nasal-type NK/T-cell lymphomas are more frequently T rather than NK lineage based on T-cell receptor gene, RNA, and protein studies: lineage does not predict clinical behavior

“…32 A novel regimen containing L-asparaginase (SMILE) had a better effect than anthracycline-based chemotherapy. 33,34 The addition of radiotherapy for earlystage nasal cases yielded survival benefits. 35 Biomarkers associated with poor prognosis included the expression of p53 and p63, and high serum levels of interleukin-9, CXCL13, serum VEGF, and survivin.…”

High-dose methotrexate, etoposide, dexamethasone and pegaspargase (MEDA) combination chemotherapy is effective for advanced and relapsed/refractory extranodal natural killer/T cell lymphoma: a retrospective study

“…However, the relapse rates were high, ranging from 25 to 40 % [1,3]. Combined chemotherapy and radiotherapy typically as concurrent chemoradiotherapy [4][5][6], and sequential l-asparaginase-based chemotherapy and sandwiched radiotherapy [7,8] significantly decreased the relapse rates and improved the long-term overall survival and progression-free survival. Patients with disseminated disease showed very poor responses to conventional anthracycline-containing regimens.…”