Does Early Postsurgical Temozolomide Plus Concomitant Radiochemotherapy Regimen Have Any Benefit in Newly-diagnosed Glioblastoma Patients? A Multi-center, Randomized, Parallel, Open-label, Phase II Clinical Trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma (GBM). However, its median overall survival (OS) is only 14.6 months. This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen.</p><p><b>METHODS</b>A randomized, parallel group, open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012. Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide (early TMZ group) or standard concomitant radiochemotherapy regimen (control group). Overall response was assessed based on objective tumor assessments, administration of corticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event (AE), and neurological condition were measured for 24 months of follow-up. The primary efficacy endpoint of this study was overall survival (OS). The secondary endpoint was progression free survival (PFS).</p><p><b>RESULTS</b>The median OS time in the early TMZ group was 17.6 months, compared with 13.2 months in the control group (log-rank test P = 0.021). In addition, the OS rate in the early TMZ group was higher at 6, 12, and 18 months than in the control group, respectively (P < 0.05). The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group (log-rank test P = 0.695). AEs occurred in 29 (55.8%) and 31(73.8%) patients respectively in early and control groups, including nausea (15.4% vs. 33.3%), vomiting (7.7% vs. 28.6%), fever (7.7% vs. 11.9%), and headache (3.8% vs. 23.8%). Only 30.8% and 33.3% were drug-related, respectively.</p><p><b>CONCLUSIONS</b>Addition of TMZ chemotherapy in the early break of the standard concomitant radiochemotherapy regimen was well tolerated and significantly improved the OS of the GBM patients, compared with standard concomitant radiochemotherapy regimen. However, a larger randomized trial is warranted to verify these results.</p>

Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells / 癌症

O6-methylguanine DNA methyltransferase (MGMT) can remove DNA alkylation adducts, thereby repairing damaged DNA and contributing to the drug resistance of gliomas to alkylating agents. In addition, glioma stem-like cells (GSCs) have been demonstrated to be involved in the recurrence and treatment resistance of gliomas. In this study, we aimed to investigate MGMT expression and regulatory mechanisms in GSCs and the association of MGMT with temozolomide (TMZ) sensitivity. GSCs were enriched from one MGMT-positive cell line (SF-767) and 7 MGMT-negative cell lines (U251, SKMG-4, SKMG-1, SF295, U87, MGR1, and MGR2) through serum-free clone culture. GSCs from the U251G, SKMG-4G, SF295G, and SKMG-1G cell lines became MGMT-positive, but those from the U87G, MGR1G, and MGR2G cell lines remained MGMT-negative. However, all the GSCs and their parental glioma cell lines were positive for nuclear factor-κB (NF-κB). In addition, GSCs were more resistant to TMZ than their parental glioma cell lines (P < 0.05). However, there was no significant difference in the 50% inhibition concentration (IC50) of TMZ between MGMT-positive and MGMT-negative GSCs (P > 0.05). When we treated the MGMT-positive GSCs with TMZ plus MG-132 (an NF-κB inhibitor), the antitumor activity was significantly enhanced compared to that of GSCs treated with TMZ alone (P <0.05). Furthermore, we found that MGMT expression decreased through the down-regulation of NF-κB expression by MG-132. Our results show that MG-132 may inhibit NF-κB expression and further decrease MGMT expression, resulting in a synergistic effect on MGMT-positive GSCs. These results indicate that enhanced MGMT expression contributes to TMZ resistance in MGMT-positive GSCs.

The clinical characteristics and treatment outcome of 57 children and adolescents with primary central nervous system germ cell tumors / 癌症

Primary central nervous system germ cell tumors (CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years (range, 2.7 to 18.0 years) at diagnosis; 43 (75.4%) had non-germinomatous germ cell tumors (NGGCTs) and 14 (24.6%) had germinomas; 44 (77.2%) had localized disease and 13 (22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB (cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months (range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival (EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs (P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively (P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs.

Nimotuzumab in combination with chemotherapy for patients with malignant gliomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Nimotuzumab is a humanized monoclonal antibody targeted against epidermal growth factor receptor (EGFR). Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment. The aim of the present study was to evaluate the efficacy and side effects of nimotuzumab in combination with chemotherapy for patients with malignant gliomas.</p><p><b>METHODS</b>The patients received 200 mg of nimotuzumab infusion intravenously over 60 minutes once weekly for the first eight weeks and then once every two weeks until unacceptable toxicity or tumor progression occurred. Individualized chemotherapy was administered based on O(6)-methylguanine-DNA methyltransferase (MGMT) expression and previous chemotherapy responses in combined with nimotuzumab.</p><p><b>RESULTS</b>Fourteen patients received a total of 122 times of nimotuzumab ranging from 2 to 20 (median 7.5 times). Combined chemotherapy regimens included: continuous 21-day temozolomide (10 cases), standard 5-day temozolomide (2 cases), teniposide plus cisplatin (1 case), and teniposide plus nimustine (1 case). Partial response (PR) and stable disease (SD) were found in 3 patients (21.4%)and 6 patients (42.9%), respectively. Disease control rate (PR + SD) was 64.3%. The median progression-free survival (PFS) was 4 months (95%CI: 0.7 - 7.3) and PFS at 6 months was 30.6%. The most common toxicities include grade I-II neutropenia (2 cases), thrombocytopenia (2 cases), lymphopenia (1 case), nausea and vomitting (3 case) and asymptomatic transaminase increase (1 case). One patient developed grade IV neutropenia and thrombocytopenia. One patient developed nimotuzumab-related acneiform rash.</p><p><b>CONCLUSIONS</b>Nimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.</p>

Nadaplatin or cisplatin combined with paclitaxol in treatment for non-small cell lung cancer: a randomized controlled study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effect, long term survival and side effect on NSCLC patients treated with nadaplatin combined with paclitaxol and cisplatin combined with paclitaxol.</p><p><b>METHODS</b>NSCLC patients with stage IIIB or IV were randomized into two groups in this prospective clinical study. TN group: nadaplatin 30 mg/m2 dl-3, paclitaxol 175 mg/m2 dl, repeated every 4 weeks. TP group: DDP 30 mg/m2 dl-3, paclitaxol 175 mg/m2 dl, repeated every 4 weeks.</p><p><b>RESULTS</b>Sixty patients were enrolled and 57 were evaluable with 30 in TN group and 27 in TP group. The overall response rate were 43.3% vs. 48.1% (P = 0.716), and the disease control rate were 86.7% vs. 88.8% in TN and TP group (P = 0.799), respectively. The median survival time was 14.3 vs. 13.0 months, and the 1- and 2-year survival rate was 62.5% vs. 59.1%, 0% vs. 5.8% in TN and TP group (P = 0.839), respectively. The rates of neutropenia and thrombocytopenia were similar in TN and TP groups whereas more patients in TP group than in TN group suffered from anemia (38.5% vs. 17.5%, P = 0.001), nausea and vomiting (82.6% vs. 35.6%, P = 0.000), fatigue (35.9% vs. 14.1%, P = 0.000) and peripheral neurotoxicity (50.0% vs. 21.9%, calculated by case, P = 0.023).</p><p><b>CONCLUSION</b>Nadaplatin combined with paclitaxol is an effective treatment regimen for NSCLC patients. When compared with similar regimen with cisplatin, the response rate and survival were similar; however, nadaplatin regimen shows some superiority as regards some treatment side effect.</p>

The clinical features of B cell lymphoblastic lymphoma and outcomes after BFM-90 regimen therapy / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the clinical features of patients with B cell lymphoblastic lymphoma(BCLL) and the outcomes after modified BFM-90 protocol therapy.</p><p><b>METHODS</b>The clinical features of 14 patients with BCLL were analysed, and compared with that of T cell lymphoblastic lymphoma in the same period. The efficacy and toxicity of modified BFM-90 protocol were analysed.</p><p><b>RESULTS</b>The 14 patients were aged 3 to 18 and diagnosed as BCLL by morphology and immunohistology. One case was in stage I , 2 stage III and 11 stage IV. Most common involved sites were lymph nodes (70% ), skin (50% ) and bone marrow (64% ). One patient received CHOP + HD-MTX, and 13 received modified BFM-90 protocol chemotherapy. Twelve patients (92.3%) achieved complete remission( CR) , 1 patient(7. 7% ) partial remission( PR). The median follow-up duration was 19. 5 months (2 to 44 months). At present 13 patients are alive except one PR patient who gave up treatment and died of disease. The major toxicity of the protocol was myelosuppression, but could be tolerated.</p><p><b>CONCLUSIONS</b>The most common involvement sites of BCLL were lymph nodes, skin and bone marrow. The effectiveness is improved as treated with modified BFM-90 protocol.</p>