- Amrubicin monotherapy for elderly patients with relapsed extensive-disease small-cell lung cancer: A retrospective study. [Journal Article]
- TCThorac Cancer 2018 Aug 20
- CONCLUSIONS: AMR may be a feasible and effective regimen for elderly patients with relapsed SCLC.
- Constitutive activation of WASp in X-linked neutropenia renders neutrophils hyperactive. [Journal Article]
- JCIJ Clin Invest 2018 Aug 20
- Congenital neutropenia is characterized by low absolute neutrophil numbers in blood, leading to recurrent bacterial infections, and patients often require life-long granulocyte CSF (G-CSF) support. X...
Congenital neutropenia is characterized by low absolute neutrophil numbers in blood, leading to recurrent bacterial infections, and patients often require life-long granulocyte CSF (G-CSF) support. X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich syndrome protein (WASp). To understand the pathophysiology in XLN and the role of WASp in neutrophils, we here examined XLN patients and 2 XLN mouse models. XLN patients had reduced myelopoiesis and extremely low blood neutrophil number. However, their neutrophils had a hyperactive phenotype and were present in normal numbers in XLN patient saliva. Murine XLN neutrophils were hyperactivated, with increased actin dynamics and migration into tissues. We provide molecular evidence that the hyperactivity of XLN neutrophils is caused by WASp in a constitutively open conformation due to contingent phosphorylation of the critical tyrosine-293 and plasma membrane localization. This renders WASp activity less dependent on regulation by PI3K. Our data show that the amplitude of WASp activity inside a cell could be enhanced by cell-surface receptor signaling even in the context in which WASp is already in an active conformation. Moreover, these data categorize XLN as an atypical congenital neutropenia in which constitutive activation of WASp in tissue neutrophils compensates for reduced myelopoiesis.
- [NAPD regimen for patients with recurrent refractory diffuse large B-cell lymphoma]. [Journal Article]
- ZNZhong Nan Da Xue Xue Bao Yi Xue Ban 2018 Jul 28; 43(7):754-759
- To investigate the clinical efficacy and toxicities for the NAPD regimen (vinorelbine, cytarabine, cisplatin, and dexamethasone) in the treatment of recurrent refractory diffuse large B-cell lymphoma...
To investigate the clinical efficacy and toxicities for the NAPD regimen (vinorelbine, cytarabine, cisplatin, and dexamethasone) in the treatment of recurrent refractory diffuse large B-cell lymphoma. Methods: A total of 30 patients identified with recurrent refractory diffuse large B-cell lymphoma were enrolled in this retrospective study. The curative efficacy of NAPD regimen was evaluated after 2 consecutive cycles. The toxicities and adverse reaction were evaluated after 1 cycle. The objective response rate (ORR), overall survival (OS), progress free survival (PFS), and the rates of 1, 2, and 4-year OS and PFS were analyzed. The prognosis was evaluated with univariate analysis. Results: The ORR was 56.7% and clinical benefit rate (CBR) was 83.3% after 2 cycles. Five patients achieved complete remission, 12 achieved partial remission, and 8 achieved stable disease. The median OS was 22 (1.5-140) months. The 1, 2, and 4-year OS rates were 59.1%, 48.2%, and 40.2%, respectively. The median PFS was 14 (1.5-140) months. The 1, 2 and 4-year PFS rates were 56.3%, 42.2%, and 31.7%, respectively. The main adverse reaction was myelosuppression. Three patients suffered from grade III-IV leukopenia and 1 thrombocytopenia. Grade I-II gastrointestinal toxicity was 20%. No heart, liver, and kidney damages at grade III-IV were observed. Conclusion: The NAPD regimen is effective and its toxicity is well tolerated for the treatment of recurrent refractory diffuse large B-cell lymphoma. It is a salvage chemotherapy regimen worth to be verified.
- Overuse and underuse of pegfilgrastim for primary prophylaxis of febrile neutropenia. [Journal Article]
- JOJ Oncol Pharm Pract 2018 Aug 19; :1078155218792698
- Introduction Guidelines recommend pegfilgrastim for primary prophylaxis of febrile neutropenia after highly myelosuppressive chemotherapy. While deviations from guidelines could result in overuse and...
Introduction Guidelines recommend pegfilgrastim for primary prophylaxis of febrile neutropenia after highly myelosuppressive chemotherapy. While deviations from guidelines could result in overuse and increased costs, underuse is also a concern and could compromise quality of care. Our objectives were to evaluate guideline adherence and quantify the extent to which physician heterogeneity may influence pegfilgrastim use. Methods We randomly sampled 550 patients from a retrospective cohort of those who received infusions at an academic cancer center between 1 September 2013 and 1 September 2014. Electronic medical and drug dispensing records provided information on patient characteristics, chemotherapy characteristics, prescribing physician, and pegfilgrastim administration. Results We included 154 patients treated by 25 physicians. About half of patients were male and mean age was 61.3 years. Forty (26.1%) patients had no febrile neutropenia risk factors, 62 (40.5%) had one, and 51 (33.3%) had two or more. Thirty patients (19.5%) received pegfilgrastim, of which 12 (40%) received palliative chemotherapy. Nine (60%) of 15 patients on a regimen with a febrile neutropenia risk ≥ 20% received pegfilgrastim. Pegfilgrastim use significantly varied by cancer type (p < 0.01), chemotherapy regimen (p < 0.001), and regimen febrile neutropenia risk (p < 0.001). Multivariable analysis reaffirmed the association between chemotherapy regimen febrile neutropenia risk ≥ 20% and pegfilgrastim use (odds ratio (OR) = 10.1, 95% confidence interval (CI): 1.6-62.7) and suggested that 31% (95% CI: 8%-71%) of the variation in use was attributable to physician characteristics. Conclusion Pegfilgrastim was potentially overused for palliative chemotherapy and underused for chemotherapy regimens with febrile neutropenia risk ≥ 20%. Successful interventions to modify prescribing practices likely require an understanding of the relationship between specific physician characteristics and pegfilgrastim use.
- Concurrent Chemoradiotherapy with Docetaxel, Cisplatin, and 5-fluorouracil Improves Survival of Patients with Advanced Esophageal Cancer Compared with Conventional Concurrent Chemoradiotherapy with Cisplatin and 5-fluorouracil. [Journal Article]
- JCJ Cancer 2018; 9(16):2765-2772
- Purpose: To compare treatment outcomes and adverse events between concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) and conventional concurrent chemoradiotherapy wi...
Purpose: To compare treatment outcomes and adverse events between concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) and conventional concurrent chemoradiotherapy with cisplatin and 5-fluorouracil (CF-RT). Methods and Materials: We retrospectively investigated treatment outcomes and adverse events in 121 patients with advanced esophageal cancer who underwent concurrent chemoradiotherapy with CF-RT (n = 83) or DCF-RT (n = 38). In the CF-RT group, patients were administered cisplatin (70 mg/m2) and 5-fluorouracil (700 mg/m2) for 5 days; in the DCF-RT group, patients were administered docetaxel (50 mg/m2), cisplatin (50 mg/m2), and 5-fluorouracil (500 mg/m2) for 5 days. The radiotherapy dose was 1.8-2 Gy per session, up to a total of 50-60 Gy. Results: The complete response (CR) rate was 37.8% in the CF-RT group and 52.6% in the DCF-RT group. Overall survival (OS) rates at 2 and 3 years were 45.0% and 37.5%, respectively, in the CF-RT group and 62.9% and 56.7%, respectively, in the DCF-RT group, with a significant intergroup difference (p = 0.032). Progression-free survival rates at 2 and 3 years were 44.1% and 36.9%, respectively, in the CF-RT group and 45.0% and 45.0%, respectively, in the DCF-RT group (p = 0.10). Local control rates at 2 and 3 years were 59.1% and 54.6%, respectively, in the CF-RT group and 71.8% and 71.8%, respectively, in the DCF-RT group (p = 0.12). The incidence of Grade 3/4 leukopenia was 55.4% (n = 46) in the CF-RT group and 78.9% (n = 30) in the DCF-RT group, with a significant intergroup difference (p = 0.022). The incidence of Grade 3/4 neutropenia was 47.0% (n = 39) in the CF-RT group and 65.8% (n = 25) in the DCF-RT group, with a notable albeit not statistically significant difference between the groups (p = 0.054). There were no significant intergroup differences in anemia, thrombocytopenia, radiation-induced dermatitis, radiation esophagitis, or late adverse events. Conclusions: Rates of OS and CR were improved after treatment with DCF-RT compared with CF-RT. Although DCF-RT-treated patients had higher rates of leukopenia, treatment safety was ensured through proper management of myelotoxicity. DCF-RT is a promising treatment regimen for advanced esophageal cancer.
- Systematic review and meta-analysis of the benefit of celecoxib in treating advanced non-small-cell lung cancer. [Journal Article]
- DDDrug Des Devel Ther 2018; 12:2455-2466
- CONCLUSIONS: Celecoxib had no benefit on survival indices for advanced NSCLC but improved the ORR of first-line treatment. Additionally, celecoxib increased the rate of hematologic toxicities without increasing the risk of cardiovascular events.
- Comparison of biosimilar filgrastim with a reference product: pharmacokinetics, pharmacodynamics, and safety profiles in healthy volunteers. [Journal Article]
- DDDrug Des Devel Ther 2018; 12:2381-2387
- CONCLUSIONS: This study has provided firm clinical evidence that the test filgrastim product is similar to its reference filgrastim product.
- Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin's lymphoma (AHOD1221): a Children's Oncology Group, multicentre single-arm, phase 1-2 trial. [Journal Article]
- LOLancet Oncol 2018 Aug 16
- CONCLUSIONS: Brentuximab vedotin with gemcitabine is a safe combination treatment with a tolerable toxicity profile for patients with primary refractory Hodgkin's lymphoma or high-risk relapse. The preliminary activity of this combination shown in this trial warrants further investigation in randomised controlled trials.
- Risk factors for septic adverse events and their impact on survival in advanced ovarian cancer patients treated with neoadjuvant chemotherapy and interval debulking surgery. [Journal Article]
- GOGynecol Oncol 2018 Aug 16
- CONCLUSIONS: Grade 3 anemia during NACT may be an early indicator for septic adverse events during adjuvant chemotherapy. Considering the adverse impact on survival, scheme and dose of adjuvant chemotherapy should be tailored, and careful follow-up evaluation should be ensured in this patient group.
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- [Diagnosis and treatment of 41 cases of head and neck Castleman's disease]. [Journal Article]
- ZEZhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2018 Aug 07; 53(8):610-614
- Objective: To explore the diagnosis and treatment of head and neck Castleman's disease (CD), and to improve the understanding of the disease. Methods: The clinical data of 41 patients with head and...
Objective: To explore the diagnosis and treatment of head and neck Castleman's disease (CD), and to improve the understanding of the disease. Methods: The clinical data of 41 patients with head and neck CD treated from January 2007 to July 2017 in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively. The patients were divided into two groups: localized CD (LCD, n=27) and multicentric CD (MCD, n=14). The clinical manifestations, laboratory examinations, operations, pathological findings and follow-up data were analyzed. Results: LCD was characterized by asymptomatic enlargement of the single lymph node with mild clinical symptoms. The main pathological type was hyaline vascular type, which can be cured by surgical treatment. MCD accompanied by fever 9 cases(64.3%), anemia 8 cases (57.1%), splenomegaly 7 cases (50.0%), respiratory symptoms 6 cases (42.9%), with multiple enlarged superficial and deep lymph nodes with pain, pleural effusion, and edema of lower extremity, C-reaction protein increased in 8 cases (57.1%), hypoproteinemia 8 cases(57.1%), globulin increased 7 cases (50.0%) and neutropenia 6 cases(42.9%). The main pathological type was plasma cell type in 7 cases (50.0%), and also there were 4 cases of hyaline vascular type and 2 cases of mixed type. Chemotherapy with or without rituximab was the main treatment. Most patients received complete or partial remission except for 2 patients who died of lung infection due to chemotherapy. Conclusions: The diagnosis of head and neck CD depends on pathological examination. LCD shows mild symptoms and good prognosis after surgery. However, clinical manifestations of MCD are complex, with relatively poor prognosis after comprehensive treatment.