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Relapse or metastatic esophageal squamous cell carcinoma (ESCC) has poor prognosis and limited treatment options. Chemotherapy based on platinum agents combined with fluorouracil or taxanes is the standard first-line treatment for it. Molecular-targeting agents, mainly epidermal growth factor receptor inhibitors including cetuximab, panitumumab, nimotuzumab and gefitinib, have failed to improve the survival of patients with advanced ESCC. Anlotinib, one of the small molecule multi-target tyrosine kinase inhibitors, can prolong the median progression free survival in patients treated with above the second line. Compared with chemotherapy, immune checkpoint inhibitors (including nivolumab, pembrolizumab and camrelizumab) significant improve overall survival times in patients with ESCC who fail to the first line chemotherapy, and can be selected as the standard second line treatment. Immunotherapy combined with chemotherapy or anti-angiogenic therapy for first-line treatment of advanced ESCC is also being studied.
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Objective:To investigate the effects of different treatment modes on the survival of patients with non-small cell lung cancer (NSCLC) brain metastases, and to evaluate the clinical values of diagnosis-specific graded prognostic assessment (DS-GPA) model and graded prognostic assessment model for lung cancer using molecular markers (Lung-molGPA).Methods:The clinical data of 195 NSCLC patients with brain metastases treated in the Cancer Hospital of Shantou University Medical College from January 2011 to December 2015 were retrospectively analyzed, including 112 patients without brain metastasis (metachronous brain metastases) at the first diagnosis, and 83 patients with brain metastases at the first diagnosis (simultaneous brain metastases). The treatment modalities of brain metastases included single local cranial radiation, chemotherapy, target therapy and combined cranial radiation with chemotherapy or target therapy, chemotherapy plus target therapy, et al. Kaplan-Meier method was used for survival analysis, Cox regression method was used for univariate and multivariate survival analyses, and DS-GPA and Lung-molGPA models were used for survival analysis.Results:The median time to brain metastases in all patients was 14.1 months (95% CI 12.2-16.0 months). The median progression-free survival (PFS BM) time of all patients was 4.3 months (95% CI 3.4-5.2 months), and the median overall survival (OS BM) time of brain metastases was 6.7 months (95% CI 4.6-8.8 months). There was no difference in PFS BM and OS BM between patients with synchronous and metachronous brain metastases ( P = 0.446, P = 0.080). Receiving anti-tumor therapy, especially combining targeted therapy could improve median OS BM. Low Karnofsky score ( RR = 1.698, 95% CI 1.238-2.329, P = 0.001) and bone metastasis ( RR = 1.505, 95%CI 1.089-2.081, P = 0.013) were independent risk factors for the OS BM of NSCLC patients with brain metastases, and chemotherapy ( RR = 0.460, 95% CI 0.289-0.731, P = 0.001) and brain radiotherapy ( RR = 0.541, 95% CI 0.391-0.749, P < 0.01) were independent protective factors for the OS BM of NSCLC patients with brain metastases. The OS BM difference between patients grouped by DS-GPA and Lung-molGPA models was statistically significant (median OS BM time of patients with DS-GPA model 0.0-1.0, 1.5-2.0 and 2.5-3.0 points were 4.2, 9.4 and 10.9 months, respectively, P = 0.015; median OS BM time of patients with Lung-molGPA model 0.0-1.0, 1.5-2.0 and 2.5-3.0 points were 4.1, 8.7 and 13.0 months, respectively, P < 0.01). Conclusions:The prognosis of NSCLC patients with brain metastases is poor, and anti-tumor therapy can prolong their survival. High Karnofsky score, without bone metastasis, receiving chemotherapy or brain radiotherapy are independent good prognostic factors for NSCLC patients with brain metastases. Both DS-GPA and Lung-molGPA models can predict the survival of NSCLC patients with brain metastases.
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PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.
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Humans , Asian People , B-Lymphocytes , Cyclophosphamide , Disease-Free Survival , Doxorubicin , Follow-Up Studies , Lymphoma, B-Cell , Prednisone , Prognosis , Rituximab , VincristineABSTRACT
Desmoplastic small round cell tumor (DSRCT) is a rare and high malignant soft tissue tumor with very poor prognosis.It usually occurs in the abdominopelvic cavity of adolescents and young males.DSRCT is prone to occur distant metastasis,mainly in the liver and lung.The histopathological manifestation is featured with nests of small round blue cells separated by desmoplastic stroma.DSRCT can co-express epithelial,neural and mesenchymal markers.The molecular characteristic of DSRCT is the production of EWSWT1 fusion protein via the translocation of chromosome t (11;22) (p13;q12).Treatments of DSRCT include radical resection or cytoreductive surgery,high intensity systemic chemotherapy,local radiotherapy and hyperthermic intraperitoneal chemotherapy.
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Objective To evaluate the effects of antitumor,toxicity and survival of second-line chemotherapy with docetaxel and capecitabine in patients with advanced esophageal squamous cell carcinoma.Methods Thirty eligible patients with measurable lesions received 1-hour intravenous treatment of docetaxel (60 mg/m2 on day 1) plus oral capecitabine (825 mg/m2 twice daily on days 1-14) every 3 weeks for up to 6 cycles.Results Patients received a median of two cycles of treatment (range 2-6).The median follow-up interview was 15.4 months (3.0-31.5 months).Intent-to-treat efficacy analysis demonstrated an overall response rate of 23.3 ％ (0 complete and 7 partial) and stability of 43.3 ％ (13 cases).The median time to progression was 3.0 months (95 ％ CI 1.929-4.071).The median survival was 8.3 months (95 ％ CI6.848-9.752).Severe adverse events (grade 3/4) reported were neutropenia (10 cases),anaemia (5 cases),thrombocytopenia (3 cases),hand-foot syndrome (4 cases),and fatigue (3 cases).Conclusion Docetaxel plus capecitabine have a manageable adverse event profile and promising activity in advance esophageal squamous cell carcinoma as a second-line treatment.
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CENP-Fisacell-cycledependentkinetochoreprotein,whoseexpressionandlocalization patterns are regulated in a cell cycle-dependent manner.CENP-F plays an important role in the development and progress of malignant tumor.The expression of CENP-F is up-regulated in many tumors.It serves as an important marker in cell proliferation.Studies have demonstrated that CENP-F is involved in tumor genesis, progress,invasiveness,relapse and prognosis.CENP-F might be a valuable prognostic marker and potential therapy target in cancer treatment.
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Objective To evaluate the association between non-Hodgkin's lymphoma (NHL) and hepatitis B virus (HBV).Methods The positive rate of hepatitis B virus surface antigen (HBsAg) in 393 patients of NHL who were admitted. The colorectal cancer patients and healthy persons were also enrolled as control. Results The positive rate of HBsAg in NHL patients (26.5 ％) was significantly higher than that in colorectal cancer patients (14.5 ％) and healthy persons (8.8 ％),respectively (x2=55.713,P＜0.001).The characteristics of HBV-infected patients with NHL were similar to those who were HBV-uninfected in terms of sex,stage and B symptoms,whereas the HBV-infected patients were younger than the HBV-uninfected patients (the median age was 47ys vs 52ys,t =-1.911,P=0.021).In the HBsAg-positive NHL group,B-cell subtype was much more common than T-cell subtype (80.8 ％ vs 15.4 ％,P=0.043).Regarding colorectal cancer patients and healthy persons as control groups,the positive rate of HBsAg was significantly higher in B-cell NHL patients than that in the control groups, respectively ( 29.6 ％ vs15.5 ％ vs 8.8 ％,Wald value were 25.174 and 55.139,respectively,P＜0.001).The positive rate of HBsAg of HBV between T-cell NHL (16.7 ％) and control groups were not significantly different. Conclusions An association is present between HBV infection and NHL,especially in B-cell subtype.
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Bisphosphonates are commonly used in patients with breast cancer to reduce skeletal-related events in metastatic disease,mitigate bone loss,and increase bone mineral density.Bisphosphonates can decrease and cleare disseminated tumor cells in bone marrow and circulation tumor cells and then prevent breast cancer relapse and metastases.Bisphosphonates can lighten tumor burden in the breast when administered with neoadjuvant chemotherapy,and improve pathology complete remission rates.Inconsistence is observed in large trials using bisphosphonates in the adjuvant setting of early breast cancer,but survival improvement is mostly seen in postmenopausal patients with low levels of estrogens.
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Objective To evaluate the association between B-cell non-Hodgkin lymphoma (NHL) and hepatitis B virus (HBV).Methods The positive rates of HBV markers in 284 patients of B-cell NHL who were admitted to our department between January 2003 and December 2009 were investigated.The positive rates of HBV markers in colorectal cancer patients were used as controls.Results The HBsAg-positive rates of patients aged 18～ 39 and stage m/Ⅳ patients were 42.6 ％ (26/61) and 37.0 ％ (50/135),which was higher than other groups.The x2 value and P value were 7.573 and 6.874,0.023 and 0.009,respectively.Compared with the control group, the B-cell NHL had significantly higher prevalence of positive HBsAg and positive HBeAg (29.6 ％ vs 14.5 ％,6.7 ％ vs 0.8 ％ ).The Wald values were 25.174 and 20.496,respectively.Both of the P value were ＜0.001 and lower prevalence of positive anti-HBs (45.4 ％ vs 58.0 ％,Wald =11.062,P =0.001).The coexpression of HBsAg, HBeAg and anti-HBc was higher in the B-NHL group than in the control group (6.0 ％ vs 0.8 ％,x2 =31.619,P ＜0.001).Similarly,the coexpression of HBsAg,anti-HBe,and anti-HBc was higher in the B-NHL group (16.2 ％ vs 11.5 ％,x2 =4.542,P =0.033).Significantly higher rate of positive anti-HBc and negative anti-HBs was observed in the B-NHL group (37.0 ％ vs 24.5 ％,Wald =17.708,P ＜ 0.001),whereas the same group showed a lower rate of negative anti-HBs compared with the control group (20.8 ％ vs 27.8 ％, Wald =5.646, P =0.017).Conclusion This finding of a positive association between HBV infection and B-NHL suggests that HBV may play an etiologic role in the induction of B-NHL.
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In recent years,mTOR inhibitors such as temsirolimus and everolimus are considered to be effective as a new generation of anti-tumor agent.Their efficacies are proven by a number of clinical trials especially in the field of overcoming the drug resistance of tumor cells.But the optimal combination regimen of the mTOR inhibitors and other anti-tumor drugs is still to be validated.
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Chemotherapy with or without molecule-targeting agents is the primary choice for patients with unresectable metastatic coloreetal cancer. New treatment strategies like intermittent therapy and maintenance therapy may not inferior to treatment until progression or unacceptable toxicity in maintaining the benefit for patients who responded or had stable disease after the first-line therapy,and also can reduce the drug related side effeets and improve the quality of life.
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Objective To evaluate the curative effect and toxicities of platinum-based double regimens for patients aged ≥ 65 with advanced non-small-cell lung cancer (NSCLC) and identify the prognosis factors. Methods 70 patients aged ≥65 with staged ⅢA-Ⅳ NSCLC, who received platinum-based double regimens as first line treatment, were emrolled.Response rates and toxicities were evaluated.Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox regression analysis was used to identify the potential prognosis factors.Results The median chemotherapy cycles was 3.The overall response rate was 41.5 % (22/53), and there was no difference between patients aged ＜70 and ≥70 (χ2 =1.945, P =0.378).The median PFS and OS were 6.0 months and 12.5 months.The chemotherapyrelated hematologic toxicities were common.Multivariate analysis revealed that performance status, numbers of metastasis, chemotherapy cycles were significant independent predictive factors for OS. Conclusion In elderly advanced NSCLC, platinum-based doublets show inspiring efficacy, but with more adverse events, and could not be all well tolerated. It should be personalized. Patients with poor performance status and multiple organs metastasis are hard to benefit from combined chemotherapy.Three to six cycles of chemotherapy is the optimal duration for patients who could be well tolerated.
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Poly ADP-Ribose Polymerase(PARP)plays an important role in the detection and repair of DNA damage.Inhibition of the PARP activity in the homologous-recombination defective cancer cell could lead to genomic instability and ultimately cause cell death.In preclinical study PARP inhibitors have demonstrated the capacity of enhancing sensitivity of cancel cells to chemotherapy agents and radiation.PARP inhibitors also showed antitumour potential in early clinical trials as monotherapy or combined with chemotherapy.
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With the development of phamacogenomic and molecular biology, it has been revealed that the curative effect of non-small-cell lung cancer (NSCLC) is closely related to tumor molecular markers. Predictive biomarkers in NSCLC patients, including ERCC1, BRCA1, hMLH1, hMSH2, RRM1, β-tubulin, TS,EGFR and K-ras, can predict individual patient's response to chemotherapy or targeted therapy, making individualized therapy be possible.
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Medical therapy is the primary choice for patients with advanced biliary tract cancer.Gemcitabine has been proved to be one of the most effective drugs and a standard regimen has been made when combined with cisplatin.Studies of the second line therapy is few.Targeted therapy has a potential to create a new era in the future but needs to be validated in large clinical trials.
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Anthracycline-based chemotherapeutic agents were extensively applied to the treatment of breast cancer. The relation of its response to TOP2A gene was proved by a number of clinical studies demonstrating that patients with both HER2 gene amplification and TOP2A gene aberration have a favored outcome,but a consensus was not yet achieved.
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OBJECTIVE@#To establish a CDDP-resistant cell line from human nasopharyngeal carcinoma and evaluate its biological characteristics.@*METHOD@#By continuously exposing and gradually increasing dose of cisplatin (CDDP), a resistant nasopharyngeal carcinoma cell line (HNE1/CDDP) was established. Drug sensitivity of this cell line was detected by MTT assay; the alterations of its biological characteristics were determined using light microscopy, cell counting and flow cytometry (FCM); its ability of adhesion, migration and invasion were also evaluated.@*RESULT@#HNE1/CDDP cell line was developed after 10 months with stable resistance to cisplatin with the resistance index was 5.83. HNE1/CDDP cell exhibited cross-resistance to many other chemotherapeutic agents (carboplatin, oxaliplatin and etoposide, etc). The morphology of HNE1/CDDP changed; doubling time prolonged; and the cell number of S-phase and G2/M-phase decreased while of G0/G1 phase increased compared with parental cells. The ability of adhesion, migration and invasion had no difference between the parental and the resistant cells.@*CONCLUSION@#HNE1/CDDP cell line shows the typical and stable resistant phenotype and can be used as a research model.
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Humans , Antineoplastic Agents , Pharmacology , Cell Line, Tumor , Cisplatin , Pharmacology , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Nasopharyngeal NeoplasmsABSTRACT
<p><b>BACKGROUND</b>Chemotherapy is one of the important treatment methods for advanced non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the efficacy of the combination of vinorelbine (NVB) and cisplatin (DDP) in the treatment of advanced NSCLC.</p><p><b>METHODS</b>Forty-eight patients with stage IIIB and IV NSCLC were treated with NVB (25mg/m² ,iv,d1 and d8) and DDP (40mg/m², d1 and d2).</p><p><b>RESULTS</b>The overall response rate (RR) was 48%, median survival time was 10 months, and 1-year survival rate was 35%. The RR of patients with first-line chemotherapy was 55%, median survival time was 11 months, the RR of patients with second-line chemotherapy was 35%, median survival time was 8 months; the RR of patients with stage IIIB was 54%, median survival time was 10 months, the RR of patients with stage IV was 41%, median survival time was 9 months. The main toxicities were myelosuppression, nausea, vomiting and phlebitis.</p><p><b>CONCLUSIONS</b>The combination of NVB and DDP in the treatment of advanced NSCLC has a high response rate and tolerable side effects, which can be adopted as the first-line treatment of advanced NSCLC, or the second line treatment that still need further studies.</p>