Combination of gemcitabine, l-asparaginase, and oxaliplatin (GELOX) is superior to EPOCH or CHOP in the treatment of patients with stage IE/IIE extranodal natural killer/T cell lymphoma: a retrospective study in a cohort of 227 patients with long-term follow-up

Abstract

Optimal treatment strategies for localized extranodal natural killer/T cell lymphoma (ENKTL) have not been fully defined. We retrospectively compared the efficacy and safety of combined gemcitabine, L-asparaginase, and oxaliplatin (GELOX) (n=38), continuous infusion of etoposide, vincristine and doxorubicin, with cyclophosphamide and prednisone (EPOCH) (n=54), or combined cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n=135) as induction chemotherapy in patients who were newly diagnosed with stage I/II ENKTL. After induction chemotherapy, the complete response (CR) rate and overall response rate (ORR) for the GELOX group were significantly higher than those in the EPOCH group (68.4 vs. 42.6%, P=0.011 for CR and 86.8 vs. 68.5%, P=0.038 for ORR). Both EPOCH and GELOX groups can attain much higher CR rates than CHOP group (CR rate was 31.8%, P<0.05). The 3-year overall survival (OS) and progression-free survival (PFS) rate were significantly better in GELOX group than in EPOCH or CHOP group (87.0 vs. 54.0 vs. 54.0% for OS, P<0.05; 72.0 vs. 50.0 vs. 43.0% for PFS, P<0.05). However, no significant differences were found between EPOCH and CHOP groups in OS or PFS (P=0.765 for OS, and 0.421 for PFS). The safety profiles were acceptable in all three groups. In conclusion, GELOX is superior to EPOCH or CHOP in the treatment of patients with stage I/II ENKTL. Further clinical trials of ENKTL should use asparaginase-based regimens as the standard chemotherapy.

Hyperglycemia decreases anti-cancer efficiency of adriamycin via AMPK pathway

“…anti-cancer agent. Given the extensive application of ADR in clinical practice (Wang et al 2014, Gladkov et al 2016, we investigated the effects of diabetes on the chemotherapeutic sensitivity of ADR. We established mouse hepatomaH22xenografts using db/db or C57 mice and mouse hepatomaH22xenografts using normal ICR mice or DM mice.…”

Radiotherapy improves survival in early stage extranodal natural killer/T cell lymphoma patients receiving asparaginase-based chemotherapy

“…L-asparaginase, which was first proposed for ENKTCL treatment by Yong, et al ., can overcome ENKTCL chemotherapy resistance and has improved patient outcomes [15–19, 20–22]. In 39 refractory and relapsed ENKTCL patients receiving radiation after vincristine, prednisolone and asparaginase-based chemotherapy, the objective response rate after treatment and 5-year OS reached 82.2% and 66.9%, respectively [15].…”

“…As a result of low anthracyclin-based chemotherapy efficacy, radiotherapy plays a vital role in treating early stage ENKTCL. L-asparaginase recently showed promising results in overcoming ENKTCL chemoresistance [15–19]. Asparaginase-based regimens, like combined dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide (SMILE), and combined asparaginase, methotrexate and dexamethasone (AspaMetDex), were effective against relapsed and refractory ENKTCL [16, 17].…”

“…The GELOX regimen, which consists of gemcitabine, oxaliplatin, and L-asparaginase, is a new induction chemotherapy. GELOX provided superior treatment outcomes and safety compared with doxorubicin-based chemotherapy in patients with previously-untreated stage I E –II E ENKTCL, with both 2-year overall survival (OS) and progression-free survival (PFS) reaching 86% [18, 19]. However, the value of radiotherapy with asparaginase-based chemotherapy remains unexplored.…”

Body mass index as a prognostic factor in patients with extranodal natural killer/T-cell lymphoma, nasal type

“…A series of studies support that patients with ENKTL can benefit from asparaginase-containing chemotherapy [7-10, 25]. Early or upfront radiotherapy is also an effective treatment to improve clinical outcome of localized disease [2, 4-6].…”