Clinical Research Of Patients With Primary Central Nervous System Lymphoma With Treatment Of Temozolomide-based Chemotherapy And Radiation Therapy

BackgroundPrimary central nervous system lymphoma (PCNSL) is a rare aggressiveextranodal non-Hodgkin lymphoma (NHL) exclusively invading the central nervoussystem and rarely spread to the outside of the central nervous system. PCNSL hasinvasive biological behavior, heterogeneous pathological morphology, atypicalclinical manifestations, and different performance of the image. The diagnosis mainlyrelies on biopsy. The purpose of the operation is to clear pathological diagnosis.Although PCNSL is sensitive to radiation therapy, the median survival of radiotherapyalone is only about12months. Studies conducted in the1990s have established thathigh-dose methotrexate-based chemotherapy added to whole brain radiotherapy(WBRT) increases survival of primary central nervous system lymphoma with themedian survival of21～51months. However, high-dose methotrexate-basedchemotherapy had great side effects, with the mortality as high as20%and heavylong-term renal toxicity. It still needed to monitoring the blood concentration andusing folic acid detoxification. The application was complicated. So it has become hotresearch area at home and abroad to looking for a less side effects and more effectivetherapeutic schedule. ObjectiveOur research is aimed at observing the efficiency and safety oftemozolomide-based chemotherapy combining with radiation therapy. The alkylatingagent temozolomide (TMZ) penetrates into the brain well and has shown someefficacy in the second-line therapy of PCNSL. TMZ can dissolve quickly after oral,with high bioavailability and small side effects, so that it is easy to accept and painless.Platinum drugs can suppress O6-methylguanine-DNA-methyltransferase (MGMT)expression in PCNSL, so as to increase the anticancer efficacy of alkylating agent.New drugs and drug-resistant mechanism research for PCNSL treatment provides anew horizon. This study is carried out based on this new situation. We evaluate therecent efficacy, side effects, and the forward curative effect to determine the value ofapplication in the treatment and to help to explore new therapeutic schedule.MethodsTwenty-four normal immune function patients who were admitted to our hospitalfrom May2006to March2012and treated with temozolomide-based chemotherapycombining with radiation therapy were retrospective analysed. Many indicators wereobserved including tumor remission, treatment-related side effects and overallsurvival in order to evaluate the safety and efficacy of the treatment through comparedwith domestic and foreigh research results. WBRT with megavoltage photons (6MV)X-ray were used once the diagnosis was established. WBRT was given five times aweek at2Gy/d until the whole brain radiotherapy dose reached40Gy. Local3dimensional conformal radiotherapy was considered when the tumor didn’t get acomplete response through a contrast enhanced MRI of the brain and spinal cord. Thepatients were given concurrent temozolomide (75mg/m2, orally) daily duringradiotherapy until the end of radiotherapy. Adjuvant chemotherapy was performedfour weeks after radiotherapy. The regimen consisted of tomozolomide (200mg/m2orally, days1-5), nedaplatin (80mg/m2i.v.,1/3dose day1-3), vincristine (1.4mg/m2i.v., day1)(TNV regimen). Each cycle was4weeks and a maximum of six cycles were applied. The treatment response was reassessed according to InternationalPCNSL Collaborative Group’(IPCG) criteria. Data processing is performed usingSPSS16.0medical statistical analysis, and drawing the survival curve in order tocomparing with literature at home and abroad.Results1The pathological results of24PCNSL patients were all diffuse large B celllymphoma with the immunohistochemical results of CD79+CD20+.2Twenty-four patients completed the chemoradiation and nineteen patientscompleted the adjuvant chemotherapy. The remaining5patients didn’t complete theadjuvant chemotherapy for the reason of heavy financial burden.3Response to treatment: complete remission (CR) in10of24(41.7%), partialremission (PR) in7of24(20%), stable disease (SD) in3of24(12.5%), progressdisease (PD) in4of24(16.7%). The objective response rate was70.8%, and medianoverall survival (OS) time was21months.4This research showed that the old patients’ median overall survival time was8months, while the young patients’ median coverall survival time was27.5months.The survival rates of1,3,5years survival rates were79.2%,29.2%,4.2%respectively.Conclusions1Therapeutic schedule of temozolomide plus concurrent WBRT followed bytemozolomide+nedaplatin+vincristine regimen as adjuvant therapy for patients withnewly diagnosed primary central nervous system lymphoma is effective with thesimilar effects to standard high dose methotrexate scheme.2Our therapeutic regimen is less side effect, good tolerability and good forpromotion3The research indicates that the age may be an independent impact factorsinfluencing the prognosis of patients with PCNSL.