Purpose :To compare the efficacy and and safety of the P-Gemox chemotherapy regimen with those of the EPOCH regimen for stage IE to IIE ENKTL.
ENKTL is an aggressive type of NHL characterized by poor survival, for which the optimal treatment strategies have not been fully defined. Radiation therapy (RT) is widely administered for patients with localized nasal disease, and produces a complete response (CR) rate of up to 70%.However, local and systemic failures are observed frequently in patients who receive RT alone.Therefore, chemotherapy is needed in combination with RT to reduce the risk of recurrence. Unfortunately, ENKTL shows a poor response to the CHOP chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) . EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide and prednisone) chemotherapy followed by involved field radiotherapy (IFRT) results in a CR rate of 75.0%. Recently, a chemotherapy regimen including gemcitabine,oxaliplatin and l-asparaginase (GELOX) has emerged, with promising results.Since 2003, a proportion of patients newly diagnosed with ENKTL were treated with the EPOCH chemotherapy regimen at some hospitals in China. From 2008, many hospitals in the southern part of China began to use the GELOX( Pegaspargase is used instead of l-asparaginase,P-Gemox).Our multicenter retrospective study showed the GELOX regimen produces a better long outcome with less toxicity than the EPOCH regimen for patients with early stage ENKTL.However,further prospective randomized clinical trials are needed to confirm the conclusion. 1. Patients * All patients should sign a written informed consent form before enrollment, and the study should be approved by the Sun Yat-sen University Cancer Center Ethics Board. * Baseline of patients: Computed tomography (CT) scans of the chest, abdomen, and pelvis, magnetic resonance imaging studies of the head and neck, and bilateral bone marrow aspiration or biopsy. Positron emission tomography-CT scans (optional). Epstein-Barr virus (E B V) DNA blood levels, titer of EBV antibody (EA-IgA, VCA-IgA), β2-micro globulin (β2-MG) , IL-9 and IL-15 in the serum. * Recheck before and after every course: Epstein-Barr virus (EBV) DNA blood levels, titer of EBV antibody (EA-IgA, VCA-IgA), β2-micro globulin (β2-MG), IL-9 and IL-15 in the serum. * Recheck every two course: Computed tomography (CT) scans of the chest, abdomen, and pelvis, magnetic resonance imaging studies of the head and neck, and bilateral bone marrow aspiration or biopsy. Positron emission tomography-CT scans (optional) 2. Treatment Protocol: * The GELOX regimen consist of the following drugs: gemcitabine ：1250 mg/ m2 on days 1,ivdrip oxaliplatin ：85 mg/m2 on day 1, ivdrip pegaspargase : 2500 IU/m 2 daily on day 1,intramuscular. The treatment cycle is repeated every 14 days. * The EPOCH regimen included a 24 h continuous infusion of etoposide (50 mg/m 2 /day), vincristine (0.4 mg/m 2 /day) and doxorubicin(10 mg/m 2 /day administered on days 1-4, followed by cyclophosphamide (750 mg/m2 /day) over 15 min intravenously on day 5 and prednisone (60 mg/m 2 /day) 60 mg/m 2 /day on days 1-5.The treatment cycle is repeated every 21 days. After at least two cycles of chemotherapy, patients who have achieved stable disease (SD) following two cycles, partial response (PR) after four cycles or complete response (CR) after six cycles of chemotherapy are referred to primary IFRT. ◦IFRT was delivered using 6-MeV linear accelerator using 3-dimensional conformable treatment planning. The IFRT dose was 56 grays (Gy) in 28 fractions, we define the clinical target volume of limited stage IE disease as the bilateral nasal cavity, bilateral ethmoid sinuses, and ipsilateral maxillary sinus; and the clinical target volume would extend to involved tissues for patients who had extensive stage IE disease. For patients who had stage IIE disease, the clinical target volume also, included the bilateral cervical lymph node area.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
gemcitabine :1250mg/m2 (ivdrip) on days 1
oxaliplatin :85 mg/m2 (ivdrip) on day 1
pegaspargase : 2500 IU/m2 (intramuscular injection)
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
progression free survival
time from the date of enrollment to date of disease progression, or death of any cause, or date of lost follow-up, whichever comes first
Time frame: up to end of follow-up-phase (approximately 3 years)
complete remission rate
The criteria for the efficacy evaluation (overall response rate and complete remission) of the regimen is according to the following article: Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999;17:1244.
Time frame: every 4 weeks,up to completion of treatment(approximately 6 months)
overall survival
overall survival (OS): time from the date of enrollment to date of death from any cause, or date of lost follow-up, whichever comes first
Time frame: .up to end of follow-up-phase (approximately 3 years)
safety, as measured by adverse events
including hematological safety and non-hematological safety.All the adverse events will be classified according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE)
Time frame: up to end of follow-up-phase (approximately 3 years)
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50 mg/m 2 /day 24 h continuous infusion on days 1-4
0.4 mg/m 2 /day 24 h continuous infusion on days 1-4
10 mg/m 2 /day 24 h continuous infusion on days 1-4
cyclophosphamide 750 mg/m2 /day over 15 min intravenously on day 5
60 mg/m 2 /day 60 mg/m 2 /day on days 1-5
IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 grays (Gy) in 25 fractions.