scholarly journals Fresh look on the urticaria problem.

2020 ◽  
Vol 17 (2) ◽  
pp. 33-43
Author(s):  
Alla O. Litovkina ◽  
Eugenii V. Smolnikov ◽  
Olga G. Elisyutina ◽  
Elena S. Fedenko
Keyword(s):  
Biological Treatment ◽  
First Line ◽  
Second Line Therapy ◽  
2Nd Generation ◽  
Line Therapy ◽  
H1 Antihistamines ◽  
Third Line Therapy ◽  
Third Line ◽  
Urticaria Treatment ◽  
Selection Of

Introduction. Nowadays urticaria is one of the most common diseases. According to the International Guidelines for the definition, classification, diagnosis and management of urticaria, 2nd-generation H1-antihistamines are recommended to be used as the first-line and second-line therapy. Omalizumab, a humanized monoclonal anti-IgE antibody, is assumed to be the third-line therapy in urticaria treatment. Summary. In this review we discuss the latest data on pathogenetic mechanisms of urticaria, focusing on the search of the new targets for the therapy. We represent the latest clinical trials of the new biological treatment for urticaria. Safety and efficiency of 4-folds higher therapeutical dose of the 2nd generation H1-antihistamines, and criteria for personalized selection of the antihistamines are discussed.

scholarly journals Effects of removing reimbursement restrictions on targeted therapy accessibility for non-small cell lung cancer treatment in Taiwan: an interrupted time series study

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e022293 ◽  
Author(s):  
Jason C Hsu ◽  
Chen-Fang Wei ◽  
Szu-Chun Yang
Keyword(s):  
Lung Cancer ◽  
Targeted Therapies ◽  
Interrupted Time Series ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

InterventionsTargeted therapies have been proven to provide clinical benefits to patients with metastatic non-small cell lung cancer (NSCLC). Gefitinib was initially approved and reimbursed as a third-line therapy for patients with advanced NSCLC by the Taiwan National Health Insurance (NHI) in 2004; subsequently it became a second-line therapy (in 2007) and further a first-line therapy (in 2011) for patients with epidermal growth factor receptor mutation-positive advanced NSCLC. Another targeted therapy, erlotinib, was initially approved as a third-line therapy in 2007, and it became a second-line therapy in 2008.ObjectivesThis study is aimed towards an exploration of the impacts of the Taiwan NHI reimbursement policies (removing reimbursement restrictions) related to accessibility of targeted therapies.SettingWe retrieved 2004–2013 claims data for all patients with lung cancer diagnoses from the NHI Research Database.Design and outcome measuresUsing an interrupted time series design and segmented regression, we estimated changes in the monthly prescribing rate by patient number and market shares by cost following each modification of the reimbursement policy for gefitinib and erlotinib for NSCLC treatment.ResultsTotally 92 220 patients with NSCLC were identified. The prescribing rate of the targeted therapies increased by 15.58%, decreased by 10.98% and increased by 6.31% following the introduction of gefitinib as a second-line treatment in 2007, erlotinib as a second-line treatment in 2008 and gefitinib as as first line treatment in 2011, respectively. The average time to prescription reduced by 65.84% and 41.59% following coverage of erlotinib by insurance and gefitinib/erlotinib as second-line treatments in 2007–2008 and following gefitinib as the first-line treatment in 2011.ConclusionsThe changes in reimbursement policies had a significant impact on the accessibility of targeted therapies for NSCLC treatment. Removing reimbursement restrictions can significantly increase the level and the speed of drug accessibility.

K-RAS codon 13 mutation in advanced colorectal cancer: A single-center retrospective study investigating prognostic outcomes and treatment strategies.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 633-633
Author(s):  
Vincenzo Dadduzio ◽  
Michele Basso ◽  
Maria Bensi ◽  
Silvia Cona ◽  
Eleonora Cerchiaro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Response To Therapy ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

633 Background: Ras genes are markers of resistance to anti-EGFR therapies. Emerging evidences suggest that each mutation, independently from its predictive role of response/resistance to specific treatments, may be expression of different diseases with different biologic behaviours. We collected data of mCRC patients harbouring K-Ras codon 13 mutation to evaluate response to therapy, PFS and OS. Methods: We retrospectively collected data of advanced colorectal cancer patients harbouring K-Ras codon 13 mutation treated at our Institution between 2004 and 2014. Results: A total of n.33 K-Ras codon 13 mutated patients were analysed. N.24 patients (72,7%) had synchronous metastatic disease. None of the patients received anti-EGFR treatment, while n.25 patients received anti-VEGF agent bevacizumab in association to chemotherapy with fluoropirimidines plus oxaliplatin and/or irinotecan (n.21 as frontline therapy, n.4 in second line). ORR was 51,5% (17/33) on first-line therapy, 22,2% (6/27) on second-line therapy and 16,6% (2/12) on third-line therapy. Median PFS was 14,1 months after first-line therapy, 9,3 months after second-line therapy, 6,4 months after third-line therapy. Median OS was 35,5 months (events: 19/33). N.14 patients received metastases surgery with radical intent. OS in this population has not been reached yet at a median follow-up of 38 months, even though all patients had a relapse. OS among patients undergone to systemic only strategy was 31 months. Conclusions: At our knowledge, this is the first report suggesting a favourable prognosis for K-ras codon 13 mutated patients, with a median overall survival even superior to pan-RAS wild-type patients. Indeed, the high percentage of advanced patients at diagnosis (72.7%), the high responsiveness to chemotherapy even in third line, the high percentage of patients converted to surgery (42.4%) in an unselected population, together with the high risk or relapse after surgery, suggest K-ras codon 13 mutated disease is probably a biologically aggressive disease. Nevertheless our data prompt that these patients may benefit aggressive strategies of treatment and multidisciplinary evaluation.

Comparasion Between Nilotinib and Dasatinib as Second-Line Therapy for Patients with Chronic Myeloid Leukemia: A Single Center Retrospective Study.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3440-3440
Author(s):  
Clarisse Lobo ◽  
Carla Boquimpani ◽  
Tania Silva Madeira ◽  
Patricia Wendling ◽  
Claudia Maximo ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Randomized Clinical Trials ◽  
Molecular Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

Abstract Abstract 3440 Nilotinib and dasatinib are second-generation tyrosine kinase inhibitors (TKI) used in patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib. There are no randomized clinical trials comparing these drugs in this context. The aim of this study was to compare, retrospectively, the hematological, cytogenetic and molecular response in patients submitted to these second-generation TKI at Hemorio, a public brazilian institution. A total of 114 patients were analyzed, 63 received nilotinib and 51 dasatinib as second-line therapy (55.3% and 44.7%, respectively). The following variables were equally distributed between these two groups (nilotinib vs. dasatinib, respectively): male sex (54% vs. 60.8%, p=0.46), median age at diagnosis (46 vs. 45 years, p=0.76), median time in months using imatinib before the switch (45.2 vs. 44.1, p=0.96), resistance to imatinib (98.4% vs. 98%, p=0.88), presence of the mutation T315I (3.2% vs. 3.9%, p=0.09), patients in chronic phase before the switch (85.7% vs. 86.3%, p=0.93). Use of another second generation TKI, as a third-line therapy, was necessary in 30 out of the 114 patients analyzed (26.1%) because of lack of response. This modification was slightly more frequent in the group initially submitted to nilotinib (31.7% vs. 19.6%, p=0.21). Patients who used a third-line therapy were excluded from response and survival analyzes. Response rates after the second-generation TKI were similar between these two groups (nilotinib vs. dasatinib): complete hematological response until three months (77.8% vs. 87.3%, p=0.24), complete cytogenetic response until six months (21.6% vs. 22.2%, p=0.95) and 12 months (32.4% vs. 33.3%, p=0.94) and major molecular response reached before 12 months (32.7% vs. 21.6%, p=0.25). Two-year overall survival (OS) and progression free-survival (PFS) were similar between these two groups (nilotinib vs. dasatinib, respectively): 92.2% vs. 87.8% (p=0.38) for OS and 87.8% vs. 83.7% (p=0.14) for PFS. Although not statistically significant, two-year OS was inferior in the group of patients who needed a third-line therapy (70.5% vs. 95.6%, p=0.70). Our results suggest that the response and survival rates are similar between nilotinib and dasatinib as second-line therapy for patients with imatinib resistant or intolerant CML. Also, they suggest an inferior prognosis for patients who need a third-line therapy. In this way, the choice between these two TKI for second-line therapy should be guided by the clinical characteristics and the mutation status of the patient. Disclosures: Lobo: NOVARTIS: Research Funding.

Sequential TKI treatments for iodine-refractory differentiated thyroid carcinomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6092-6092
Author(s):  
Christelle de la Fouchardiere ◽  
Marie-Helene Massicotte ◽  
Isabelle Borget ◽  
Maryse Brassard ◽  
Mederic Claude-Desroches ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Specific Treatment ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Off Label ◽  
Line Therapy ◽  
Number Of Patients ◽  
Third Line Therapy ◽  
Third Line

6092 Background: Tyrosine kinase inhibitors (TKI) are currently used to treat patients with advanced iodine-refractory differentiated thyroid cancers (DTC) but none has been approved by the FDA or the EMA until now. Sometimes, patients are treated with off-label TKI when a clinical trial is not available or in second- and third-line therapy. Methods: We hereby report the efficacy of “off-label” sorafenib and sunitinib treatments as first-, second- and third-line therapy in metastatic DTC patients from the French TUTHYREF (TUmeurs THYroïdiennes REFractaires) network. Primary endpoints were progression free survival (PFS) and tumor response according to sequential TKI treatment. Secondary endpoint was organ-specific metastatic site analysis. Results: 45 patients with advanced iodine-refractory DTC treated with off-label TKI were included in this study (26 men, mean age: 62 years). 22 had papillary, 10 had follicular and 13 had poorly DTC. 24/45 patients were treated with two and 3/45 with three lines of TKIs. Sorafenib was the most frequently used (57%) followed by sunitinib (21.5%) and vandetanib (21.5%). Partial response (PR) rate was of 29% in the 21 patients who received first-line sorafenib therapy whereas PR was observed in 57% of the 7 first-line sunitinib patients. There was no PR with second- (n=24) and third-line (n=3) treatments. However, median progression free survival (PFS) was similar in second- as compared to first-line sorafenib or sunitinib treatment (6.7 vs. 7.6 months, HR 0.85 (95CI 0.45-1.61) p=0.6). Liver metastases were the most responsive to treatment (n=7; mean of -30%), followed by lung (n=57; mean of -19%) and lymph node (n=43; mean of -13%) metastases. Bone (n=14) and pleural (n=9) lesions were the most refractory to treatment (mean of -1% and -5%, respectively). Conclusions: Due to the small number of patients, we could not recommend a specific treatment sequence (sorafenib then sunitinib) over another (sunitinib then sorafenib). But TKI therapy appears to be beneficial in refractory DTC patients even in second- and third-line therapy, with similar PFS and stable disease as best response. Bone and pleural metastases were the most refractory and liver lesions the most responsive to treatment.

Third-line therapy in metastatic renal cell carcinoma: Results from the International mRCC Database Consortium.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 430-430 ◽  
Author(s):  
Daniel Yick Chin Heng ◽  
Connor Wells ◽  
Frede Donskov ◽  
Brian I. Rini ◽  
Jae-Lyun Lee ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Second Line ◽  
Second Line Therapy ◽  
Therapy Initiation ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

430 Background: Third-line targeted therapy efficacy in metastatic renal cell carcinoma (mRCC) is not well characterized and many funding bodies do not provide reimbursement for it. Methods: The International mRCC Database Consortium (IMDC) consists of consecutive patient series from 25 cancer centers. It was queried for specific sequences of targeted therapy and third-line therapy. Kaplan Meier estimates were used for survival. Cox proportional hazards models were used to adjust hazard ratios for confounders. Patients that stopped second-line therapy were divided into two groups: those that went onto third-line therapy and those did not. Results: 4,050 patients were treated with first-line targeted therapy, of which 2,011 (49.6%) had second-line therapy and 879 (21.7%) had third-line targeted therapy. The most common third-line therapies were everolimus 25%, sorafenib 14%, sunitinib 13%, temsirolimus 11%, pazopanib 10%, and axitinib 6%. IMDC prognostic groups at third-line therapy initiation were 6% favorable risk, 67% intermediate risk, and 27% poor risk. Overall response rate for third-line therapy was 10.5% and 50.9% had stable disease in those patients that were evaluable. Median PFS was 5.1 months (95% CI, 4.5-5.7) and median OS from third-line therapy initiation was 12.0 months (95% CI, 10.7-12.9). Patients stopping second-line therapy that move on to third-line therapy vs. those that do not receive third line therapy have a median OS from stopping second-line therapy of 13.1 vs. 2.3 mons (p<0.0001). When adjusted for second-line IMDC prognostic criteria and KPS at second-line treatment cessation, patients who do receive third-line therapy have a HR of death of 0.41 (95% CI, 0.32-0.52; p<0.0001) compared to those that do not receive third-line therapy. This may be in part due to patient selection. To further limit bias, when excluding patients that live less than 3 months after second-line therapy cessation, the adjusted HR was similar. Conclusions: Third-line targeted therapy has demonstrated activity and is prevalent in use. Further studies are required to determine appropriate sequencing.

Response to systemic therapy in patients with metastatic fumarate hydratase (FH) deficient renal cell carcinoma (RCC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 686-686
Author(s):  
Jack Patrick Gleeson ◽  
Ines Nikolovski ◽  
Ritesh Kotecha ◽  
Yasser Ged ◽  
Natalie Shapnik ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Systemic Therapy ◽  
Objective Response ◽  
Fumarate Hydratase ◽  
First Line ◽  
Line Therapy ◽  
Pathologic Features ◽  
Third Line Therapy ◽  
Third Line ◽  
Peritoneal Spread

686 Background: FH-deficient RCC (FHRCC) is characterized by unique pathologic features and lack of FH staining on immunohistochemistry (IHC). Most cases are associated with germline FH mutations and poor prognosis, but there is limited data on the efficacy of systemic therapy. Methods: Patients with metastatic FHRCC, defined by presence of FH germline or somatic mutation with loss of FH by IHC [FH and 2-succino-cysteine (2SC)], were identified from an institutional database. Clinical and treatment data was obtained from electronic records. The primary outcome was best objective response rate to first, second or third-line systemic therapy by blinded investigator RECIST v1.1 assessment. Results: 32 patients (median age 46; range 20-74; M:F, 20:12) were identified. All patients had evidence of FH-deficiency by IHC, 23 (72%) had germline FH mutations, 9 (28%) had somatic only FH mutations. 20 patients (62.5%) presented with de novo metastatic disease. Most common sites of metastasis were retroperitoneal lymph nodes (82%), lung (78%) and peritoneal spread (70%); no patients developed brain metastases. Median overall survival (OS) from diagnosis of metastatic disease is 28.1 months (95% CI: 14.9, 33.8). Median follow-up is 14.8 months. 25 patients were evaluable for response to first-line therapy, 5 to second-line and 4 to third-line therapy (Table). Most common first-line therapies were combination mTOR/VEGFR (50%) and VEGFR monotherapy (20%). ORR to first, second and third-line therapy was 40%, 20% and 25%, with no complete responses. 8 patients who received IO monotherapy were evaluable; 3 had stable disease, no responses were seen. Conclusions: Patients with FHRCC show distinct patterns of disease progression with primary peritoneal spread. Although there was high ORR to VEGFR/mTOR inhibitor combinations, there were limited responses to IO monotherapy.[Table: see text]

Cardiotoxicity of Oral Methadone as an Analgesic–-Recommendations for Safe Use

2009 ◽  
Vol 1 ◽  
pp. CMT.S3041 ◽  
Author(s):  
David R.P. Guay
Keyword(s):  
English Language ◽  
Cardiac Safety ◽  
Second Line Therapy ◽  
The Past ◽  
Line Therapy ◽  
Oral Methadone ◽  
Third Line Therapy ◽  
Third Line ◽  
Epidemiologic Risk ◽  
Epidemiologic Risk Factor

Once used only as third-line therapy in the management of chronic pain states, methadone is now being used as first- and second-line therapy. Most risks and the stigma associated with methadone use have been known for years. Only over the past decade or so have the unique pharmacokinetic-pharmacodynamic properties and methods for conversion from other opioids to methadone been established. Pertinent English-language literature was obtained from MEDLINE/PUBMED and EMBASE searches (1966-June 2009). This paper provides an overview of the cardiotoxicity of oral methadone, with an emphasis on its use as an analgesic. Cardiotoxicity during its use in the maintenance of opioid addiction has also been reviewed due to the wealth of epidemiologic, risk factor, and correlative analytic data contained therein. A series of recommendations are provided to improve the cardiac safety profile of oral methadone used for analgesia. In addition, there is a discussion of settings and patient types which may impact upon these recommendations.

scholarly journals Contemporary Treatment Patterns and Response in Relapsed/Refractory Cutaneous T-Cell Lymphoma (CTCL) across Five European Countries

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 145
Author(s):  
Chalid Assaf ◽  
Nathalie Waser ◽  
Martine Bagot ◽  
Mary He ◽  
Tina Li ◽  
...  
Keyword(s):  
T Cell ◽  
Systemic Therapy ◽  
Cell Lymphoma ◽  
Treatment Patterns ◽  
Second Line ◽  
Cutaneous T Cell Lymphoma ◽  
First Line ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

The treatment pattern of cutaneous T-cell lymphoma (CTCL) remains diverse and patient-tailored. The objective of this study was to describe the treatment patterns and outcomes in CTCL patients who were refractory or had relapsed (R/R) after a systemic therapy. A retrospective chart review study was conducted at 27 sites in France, Germany, Italy, Spain and the United Kingdom (UK) of patients who received a first course of systemic therapy and relapsed or were refractory. Data were collected longitudinally from diagnosis to first-, second- and third-line therapy. The study included 157 patients, with a median follow-up of 3.2 years. In total, 151 proceeded to second-line and 90 to third-line therapy. In the first line (n = 147), patients were treated with diverse therapies, including single- and multi-agent chemotherapy in 67 (46%), retinoids in 39 (27%), interferon in 31 (21%), ECP in 4 (3%), corticosteroids in 3 (2%) and new biological agents in 3 (2%). In the second line, the use of chemotherapy and retinoids remained similar to the first line, while the use of new biologics increased slightly. In sharp contrast to the first line, combination chemotherapy was extremely diverse. In the third line, the use of chemotherapy remained high and diverse as in the second line. From the time of first R/R, the median PFS was 1.2 years and the median OS was 11.5 years. The presented real-world data on the current treatments used in the management of R/R CTCL in Europe demonstrate the significant heterogeneity of systemic therapies and combination therapies, as expected from the European guidelines.

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