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- Pegfilgrastim is a pegylated granulocyte colony-stimulating factor that is FDA-approved to decrease the risk of patients developing febrile neutropenia when receiving myelosuppressive chemotherapy re...
Pegfilgrastim is a pegylated granulocyte colony-stimulating factor that is FDA-approved to decrease the risk of patients developing febrile neutropenia when receiving myelosuppressive chemotherapy regimens. For primary prophylaxis, the risk of developing febrile neutropenia should be 20% or higher, and there should be no other safer regimen that is equally effective available to the patient. A patient's chance for developing febrile neutropenia is determined by definable risk factors, listed here:
- Emerging cell cycle inhibitors for treating metastatic castration-resistant prostate cancer. [Journal Article]
- EOExpert Opin Emerg Drugs 2018 Nov 13
- Introduction Disease progression despite androgen suppression defines lethal castration-resistant prostate cancer (CRPC). Most of these cancers remain androgen receptor (AR)-signalling dependent. The...
Introduction Disease progression despite androgen suppression defines lethal castration-resistant prostate cancer (CRPC). Most of these cancers remain androgen receptor (AR)-signalling dependent. Therapy for metastatic CRPC includes abiraterone acetate, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, and radium-223. However, survival remains modest for men with progressive disease despite AR-targeted therapy and docetaxel, and therefore novel treatments are needed. Areas covered Recent evidence of genomic heterogeneity and sensitivity to PARP inhibitors supports investigation of targeted agents in CRPC. Cell cycle inhibitors are therefore logical molecules to investigate. Review of the current literature identified cell cycle inhibitors under study in early phase clinical trials targeting the G1 (palbociclib, ribociclib, AZD-5363, ipatasertib), S (M-6620, prexasertib), G2 (adavosertib) and M (alisertib) phases of the cell cycle. Expert opinion Strategies combining cell cycle inhibitors with active agents in CRPC are most likely to have clinical impact with CDK4/6 and Wee1 inhibitors appearing most promising. Identification of predictive biomarkers may be essential and currently trials are testing circulating cell-free DNA as an approach. Incremental toxicities such as neutropenia are important in this population. Results from most current clinical trials of cell cycle inhibitors in CRPC are still pending but it is anticipated they will provide important insights into the heterogeneous biology of CRPC.
- Pathogenic significance of hemorrhagic pneumonia in hematologic malignancy patients with Stenotrophomonas maltophilia bacteremia: clinical and microbiological analysis. [Journal Article]
- EJEur J Clin Microbiol Infect Dis 2018 Nov 12
- Hemorrhagic pneumonia (HP) is known as the clinical manifestation of Stenotrophomonas maltophilia infection, while catheter-related blood stream infection (CRBSI) is the common clinical presentation ...
Hemorrhagic pneumonia (HP) is known as the clinical manifestation of Stenotrophomonas maltophilia infection, while catheter-related blood stream infection (CRBSI) is the common clinical presentation of S. maltophilia bacteremia (SMB). The purpose of this study is to evaluate the risk factors for mortality in hematologic malignancy patients with SMB and to analyze clinical and microbiological characteristics of HP associated with SMB and CRBSI. SMB cases of patients with a hematologic malignancy were collected from 2006 through 2016. The overall 30-day mortality rate and mortality risk factors were assessed. The expression of major virulence-associated genes from S. maltophilia isolates, which included genes encoding type-1 fimbriae (smf-1), proteases (StmPr1 and StmPr2), and esterase (Smlt3773), from the blood of patients with HP and CRBSI was investigated. The phenotypic and genotypic traits were also compared. A total of 118 cases of SMB were included. The overall 30-day mortality rate was 61.0%. A multivariable analysis showed that HP was the most important risk factor for mortality (adjusted OR = 106.41; 95% CI = 5.18-2184.55). Although no statistical significance was observed in microbiological analysis, isolates from HP have a trend toward a higher protease activity (93.8% vs. 73.3%, P = 0.172). Clinical analysis showed that thrombocytopenia (P = 0.037) and prolonged neutropenia (P = 0.043) were significant factors associated with HP. Our data, which includes hematologic malignancy patients with SMB, suggest that HP is the significant risk factor for mortality and that the unique characteristics of patients and microbes contribute to the pathogenesis.
- Early neutropenia with thrombocytopenia following alemtuzumab treatment for multiple sclerosis: case report and review of literature. [Journal Article]
- CNClin Neurol Neurosurg 2018 Nov 03; 175:134-136
- Alemtuzumab is a monoclonal antibody targeting the CD52 antigen used in the treatment of relapsing-remitting multiple sclerosis (RRMS). CD52 is expressed by lymphocytes and monocytes but less by neut...
Alemtuzumab is a monoclonal antibody targeting the CD52 antigen used in the treatment of relapsing-remitting multiple sclerosis (RRMS). CD52 is expressed by lymphocytes and monocytes but less by neutrophils and not by platelets. We present a case of a 38-year-old woman with RRMS who developed early neutropenia with thrombocytopenia after alemtuzumab infusion. She had no fever or symptoms of infection or purpura. After two weeks her haematological disorders spontaneously resolved. We reported the first case of neutropenia and thrombocytopenia as a possible event occurring after alemtuzumab infusion in MS patients, even if in a mild grade. So, we recommend to not underestimate these two conditions.
- Usefulness of guideline recommendations for prognosis in patients with candidemia. [Journal Article]
- MMMed Mycol 2018 Nov 10
- We aimed to analyze whether the lack of inclusion of specific recommendations for the management of candidemia is an independent risk factor for early and overall mortality. Multicenter study of adul...
We aimed to analyze whether the lack of inclusion of specific recommendations for the management of candidemia is an independent risk factor for early and overall mortality. Multicenter study of adult patients with candidemia in 13 hospitals. We assessed the proportion of patients on whom nine specific ESCMID and IDSA guidelines recommendations had been applied, and analyzed its impact on mortality. 455 episodes of candidemia were documented. Patients who died within the first 48 hours were excluded. Sixty-two percent of patients received an appropriate antifungal treatment. Either echinocandin or amphotericin B therapy were administered in 43% of patients presenting septic shock and in 71% of those with neutropenia. Sixty-one percent of patients with breakthrough candidemia underwent a change in antifungal drug class. Venous catheters were removed in 79% of cases. Follow-up blood cultures were performed in 72% of cases. Ophthalmoscopy and echocardiogram were performed in 48% and 50% of patients, respectively. Length of treatment was appropriate in 78% of cases. Early (2-7 days) and overall (2-30 days) mortality were 8% and 27.7%, respectively. Inclusion of less than 50% of the specific recommendations was independently associated with a higher early (HR = 7.02, 95% CI: 2.97-16.57; P < .001) and overall mortality (HR = 3.55, 95% CI: 2.24-5.64; P < .001). In conclusion, ESCMID and IDSA guideline recommendations were not performed on a significant number of patients. Lack of inclusion of these recommendations proved to be an independent risk factor for early and overall mortality.
- Distribution of Extreme Vital Signs and Complete Blood Count Values of Healthy Parturients: A Retrospective Database Analysis and Review of the Literature. [Journal Article]
- A&AAnesth Analg 2018 Nov 09
- CONCLUSIONS: Our findings justify the practice of using ≥2 repeated measurements for diagnosing hypertensive disorders of pregnancy. Lower normal blood pressure limits may be below those defining hypotensive shock. Normal heart rates exceed the accepted definitions of both tachy- and bradycardia. Normal temperatures at all times have a more narrow range than previously thought, and the normal range of white blood cell count has outliers exceeding the current definitions of leukocytosis or leukopenia at all times. The normal lower range of hemoglobin was constantly below 10 g/dL, and normal platelet counts were considerably lower than those previously described. The vital signs and complete blood count values thus far considered normal for the peripartum period may require some adjustment. New definitions for hypotension, tachy- and bradycardia, fever, and leukocyte quantitative disorders should be considered.
- A Phase Ib Study of the FGFR/VEGFR Inhibitor Dovitinib With Gemcitabine and Capecitabine in Advanced Solid Tumor and Pancreatic Cancer Patients. [Journal Article]
- AJAm J Clin Oncol 2018 Nov 08
- CONCLUSIONS: Dovitinib 300 mg daily is the recommended dose when combined with gemcitabine and capecitabine, achieving clinically relevant plasma concentrations. The study combination demonstrated encouraging efficacy signals in advanced pancreatic cancer.
- Analytical Comparison of the Originator Granulocyte-colony Stimulating Factor Filgrastim and its Biosimilars. [Journal Article]
- CPCurr Pharm Des 2018 Nov 09
- CONCLUSIONS: This study shows that a high level of similarity is maintained among originator and three biosimilar filgrastims up to 5 years from their first registration in the EU.
- Predictive value of ERCC1, ERCC2, ERCC4, and glutathione S-Transferase Pi expression for the efficacy and safety of FOLFIRINOX in patients with unresectable pancreatic cancer. [Journal Article]
- AJAm J Cancer Res 2018; 8(10):2096-2105
- The platinum-based chemotherapy regimen FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) is currently used as a standard treatment for patients with unresectable pancreatic cancer. ...
The platinum-based chemotherapy regimen FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) is currently used as a standard treatment for patients with unresectable pancreatic cancer. FOLFIRINOX is associated with severe toxicities, including neutropenia, febrile neutropenia, and anorexia; however, there are currently no reliable biomarkers to predict its efficacy and safety. Several studies of patients with various cancers have shown that tumor expression of excision repair cross-complementing (ERCC) proteins and glutathione S-transferase Pi (GSTPi) correlates with the response to platinum-based chemotherapies. Therefore, in this study, we examined the associations between expression of ERCC proteins and GSTPi and the safety and efficacy of FOLFIRINOX in 34 patients with unresectable pancreatic cancer. ERCC1, ERCC2, ERCC4, and GSTPi expression were examined by immunohistochemical staining of tumor specimens and the results were correlated with overall survival, progression-free survival, response rate, disease control rate, and the frequency of grade 3-4 neutropenia and non-hematologic toxicities. We found that ERCC1, ERCC2, ERCC4, and GSTPi were expressed in tumor samples from 64%, 24%, 18%, and 64% of patients, respectively. Notably, there were no statistically significant associations between the expression pattern of any of the proteins and either the clinical outcomes or the frequency of grade 3-4 neutropenia or grade 3-4 anorexia. Collectively, these data indicate that tumor expression of ERCC1, ERCC2, ERCC4, and GSTPi does not predict the safety or efficacy of FOLFIRINOX in patients with pancreatic cancer.
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- A phase I/II study of bexarotene with carboplatin and weekly paclitaxel for the treatment of patients with advanced non-small cell lung cancer. [Journal Article]
- JTJ Thorac Dis 2018; 10(9):5531-5537
- CONCLUSIONS: The 43% 1-year survival for patients receiving bexarotene with weekly paclitaxel and monthly carboplatin is encouraging. With the availability of new classes of agents for lung cancer, further evaluation of this regimen in unselected patients is not warranted. Our study confirms prior subgroup analyses showing a significant correlation between bexarotene-induced hypertriglyceridemia and survival. Further research is needed to identify molecular biomarkers to identify this subset of patients and to explore rexinoids in other combinations, especially with immunotherapy.