| Backgrounds and ObjectiveLymphoma is a malignant tumor associated with lymph nodes and peripheral lymphocytes,mainly lymph nodes,which can easily invade the bone marrow,gastrointestinal tract,nervous system and so on.With the application of molecular biology technology in the blood system,the immediate and long-term efficacy of lymphoma had improved obviously owing to pervasive understanding in incidence factors and mechanism of lymphoma,molecular biological characteristics of disease subtypes,epigenetic therapy and targeted therapy.However,conventional treatment cannot obtain satisfied effect in relapsed patients or people who had high risk factors with 20%~30%of patients cannot achieve complete remission.Among numerous clinical factors,influencing the curative effect,inappropriate treatment regimen,incomplete treatment regimen and therapeutic trial without existing treatment regimen may result in recurrence or refractory lymphoma.High-dose chemotherapy and autologous stem cell transplantation are the main salvage treatments for recurrence or refractory non-Hodgkin lymphoma.However,such treatments have certain limitations and are more suitable for young patients who are still sensitive to chemotherapy.As a novel small molecule vascular endothelial growth factor receptor-2(VEGFR-2)tyrosine kinase inhibitor,apatinib could strongly inhibit new angiogenesis in tumor tissue by highly selective compete the ATP binding site to block downstream signal transduction.Apatinib has been approved and launched in People’s Republic of China in 2014 as a subsequent-line treatment for patients with advanced gastric cancer(AGC)due to the favorable survival benefit it showed in gastric cancer phase III clinical trial.It has not yet been approved for treatment of other malignancies,but clinical trials have been carried out in a variety of solid tumors.This article aims to evaluate the efficacy and safety of apatinib in recurrence or refractory non-Hodgkin lymphoma patients,and provide more options for salvage treatment.MethodsTo determine treatment patterns and associated outcomes in recurrence(defined as being confirmed disease progression after received complete remission after treatment recently)or refractory(defined as treatment of disease has not been achieved stable after 2 cycles,or partial response after treatment of 4 cycle,or complete response after 6 cycle)NHL a retrospective analysis was undertaken at our hospital network among patients treated between February 2016 and January 2017.The inclusion criteria were as follow:(1)Age from 14-70,all patients have received at least two or more lines chemotherapy,and disease progression occurred.(2)At least one measurable lesion(measurable lesion was defined as:the longest diameter>1.5cm or the external lesion of the lymph node lesion in the CT cross-sectional image>1.0cm;and FDG-PET positive lesions).(3)ECOG score 0-2points.(4)Laboratory examination value within 7 days must meet the following criteria before receiving treatment:blood routine examination(without blood transfusion,G-CSF or drugs to correct within 14 days):Hb 80 g/L or higher;ANC≥1.0×10~9/L,PLT≥75×10~9/L.Biochemical examination:TBIL≤1.5×ULN;ALT and AST are less than or equal to 2.5×ULN;Serum Cr≤1.25×ULN or endogenous creatinine clearance≤45mL/min(Cockcroft-Gault formula).Coagulant function:the international standardization ratio(INR)1.5×ULN or less;activated partial thromboplastin time(APTT)is less than or equal to 1.5×ULN.(5)No other related treatment includes Chinese medicine,immunotherapy,and biotherapy(except for the treatment of bone metastasis and other symptoms).(6)Excluding other major diseases,the heart function is normal.31patients were enrolled.Treatment comprised of oral apatinib 500mg once daily with 21 days as a treatment cycle.The efficacy was evaluated in every 2 cycles and all the adverse reactions were recorded.After 6 cycles of treatment,the curative effect was evaluated every 3months,and PFS and OS were recorded.Kaplan-Meier method was used for survival analysis.ResultsFrom February 2016 to January 2017,31 patients who received oral apatinib treatment were eligible.There were 19 males and 12 females,including 15 cases of DLBCL,2 cases of FL,3 cases of MCL,5 cases of PTCL,and 6 cases of ENKT.There were 14 patients in phase I-II and 17 in stage III-IV.Among all the patients,12were associated with B symptoms,16 cases with elevated serum LDH,7 patients with bone marrow invasion,and 13 patients with elevated serumβ2 microglobulin.In the short-term curative effect,3 cases got CR,7 cases were PR,5 cases were SD,and 16 cases were PD.The 1-year PFS and 1-year OS were 45.8%and 67.7%,respectively.The median PFS was 8.5 months,and the median OS was not reached.The total effective rate(ORR)was 32.3%,and the disease control rate(DCR)was48.4%.All the adverse reactions were completely recorded,including the time,the nature of adverse reactions,the degree of occurrence,duration,the degree of correlation with drug use,treatment adjustment or interruption,treatment methods and outcomes.And all the AEs were divided into 0-5 degree according to the evaluation standard of adverse reactions(CTCAE V4.03).Most of the patients had grade 1/2 adverse events.The most common non-hematologic adverse events were proteinuria,hypertension,and hand foot syndrome,the incidence of which was45.2%,38.7%and 32.3%,respectively.The adverse reactions were well tolerated,the incidence of grade 3/4 adverse events was low,no fatal hematological toxicity occurred,and no severe infection and cerebral hemorrhage occurred during the period of myelosuppression.After stopping treatment,stimulating bone marrow hematopoiesis and lowering blood pressure,all of them improved or controlled after treatment.ConclusionThe results showed apatinib might have a rapid,safe and high efficacy on R/R NHL patients. |
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