Bichat guidelines for the clinical management of plague and bioterrorism-related plague

Yersinia pestis appears to be a good candidate agent for a bioterrorist attack. The use of an aerosolised form of this agent could cause an explosive outbreak of primary plague pneumonia. The bacteria could be used also to infect the rodent population and then spread to humans. Most of the therapeutic guidelines suggest using gentamicin or streptomycin as first line therapy with ciprofloxacin as optional treatment. Persons who come in contact with patients with pneumonic plague should receive antibiotic prophylaxis with doxycycline or ciprofloxacin for 7 days. Prevention of human-to-human transmission via patients with plague pneumonia can be achieved by implementing standard isolation procedures until at least 4 days of antibiotic treatment have been administered. For the other clinical types of the disease, patients should be isolated for the first 48 hours after the initiation of treatment.

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Hepatic reserve and the other conditions for regorafenib as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib in Japanese practical setting

Annals of Oncology ◽

10.1093/annonc/mdx660.047 ◽

2017 ◽

Vol 28 ◽

pp. x71

Author(s):

T. Terashima ◽

T. Yamashita ◽

K. Arai ◽

S. Kaneko

Keyword(s):

Hepatocellular Carcinoma ◽

The Other ◽

Advanced Hepatocellular Carcinoma ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Hepatic Reserve ◽

First Line Therapy ◽

Line Therapy

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Clinical Option of Pemetrexed-Based Versus Paclitaxel-Based First-Line Chemotherapeutic Regimens in Combination With Bevacizumab for Advanced Non-Squamous Non-Small-Cell Lung Cancer and Optimal Maintenance Therapy: Evidence From a Meta-Analysis of Randomized Control Trials

10.21203/rs.3.rs-43694/v1 ◽

2020 ◽

Author(s):

Le-Tian Huang ◽

Rui Cao ◽

Yan-Ru Wang ◽

Li Sun ◽

Xiang-Yan Zhang ◽

...

Keyword(s):

Maintenance Treatment ◽

Meta Analysis ◽

Small Cell ◽

The Other ◽

Small Cell Lung ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Oncogenic Driver ◽

Grade 3

Abstract Background: In the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy. Methods: All eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP±B) and paclitaxel-carboplatin with bevacizumab (PC+B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem+B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events.Results: Data of 3,139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP±B and PC+B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP±B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC+B (all P<0.05). PP±B resulted in higher rates of grade 3/4 anemia and thrombocytopenia, but lower rates of neutropenia, febrile neutropenia, and sensory neuropathy than PC+B (all P<0.001). The other three RCTs were included in an analysis that compared Pem+B and B as a maintenance treatment. Compared with B, Pem+B maintenance treatment resulted in significant improvements in OS (HR, 0.88), PFS (HR, 0.64), and PFSR1y (RR, 0.70), but higher rates of anemia, thrombocytopenia, and neutropenia (all P<0.001).Conclusion: Although the first-line PP+B regimen had longer PFS and PFSR1y than the PC+B regimen, no OS difference was observed. Addition of pemetrexed to bevacizumab as maintenance therapy significantly improved OS compared with bevacizumab maintenance alone, but led to more toxicity.

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Effectiveness of long-term cabergoline treatment for giant prolactinoma: study of 12 men

Acta Endocrinologica ◽

10.1530/eje-06-0646 ◽

2007 ◽

Vol 156 (2) ◽

pp. 225-231 ◽

Cited By ~ 69

Author(s):

Ilan Shimon ◽

Carlos Benbassat ◽

Moshe Hadani

Keyword(s):

Visual Field ◽

The Other ◽

Serum Prolactin ◽

Visual Field Defects ◽

First Line ◽

Giant Prolactinoma ◽

First Line Therapy ◽

Line Therapy ◽

Giant Prolactinomas ◽

Field Defects

Objective: To review our experience with cabergoline, a D2-selective dopamine agonist, for the treatment of giant prolactinomas. Design: A retrospective case series; descriptive statistics. Methods: The study group included 12 men aged 24–52 years (mean 39.2 years) treated for giant prolactinoma at our centers from 1997 to 2006. Cabergoline was started at a dose of 0.5 mg/three times a week and progressively increased as necessary to up to 7 mg/week. Patients were followed by hormone measurements, sellar magnetic resonance imaging, and visual examinations. Results: In ten patients, cabergoline served as first-line therapy. The other two patients had previously undergone transsphenoidal partial tumor resection because of visual deterioration. Mean serum prolactin level before treatment was 14 393 ± 14 579 ng/ml (range 2047–55 033 ng/ml; normal 5–17 ng/ml). Following treatment, levels normalized in ten men within 1–84 months (mean, 25.3 months) and decreased in the other two to 2–3 times of normal. Tumor diameter, which measured 40–70 mm at diagnosis, showed a mean maximal decrease of 47 ± 21%; response was first noted about 6 months after the onset of treatment. Nine patients had visual field defects at diagnosis; vision returned to normal in three of them and improved in five. Testosterone levels, initially low in all patients, normalized in eight. There were no side effects of treatment. Conclusion: Cabergoline therapy appears to be effective and safe in men with giant prolactinomas. These findings suggest that cabergoline should be the first-line therapy for aggressive prolactinomas, even in patients with visual field defects.

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Patterns of imatinib resistance mutation analysis in chronic myeloid leukemia (CML) patients on imatinib at the time of loss of response to the drug in Asian Indian subjects

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.7079 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 7079-7079

Author(s):

K. Prabhash ◽

T. Vora ◽

N. S. Ghadyalpatil ◽

B. Rangarajan ◽

S. S. Hingmire ◽

...

Keyword(s):

Drug Resistance ◽

Mutation Analysis ◽

Resistance Mutation ◽

The Other ◽

Molecular Response ◽

First Line ◽

Imatinib Resistance ◽

Loss Of Response ◽

First Line Therapy ◽

Line Therapy

7079 Background: The treatment of (CML) has undergone major changes in the past decade with the introduction of tyrosine kinase inhibitors (TKI). However the initial enthusiasm is waning with increasing recognition of drug resistance. There is an urgent need to identify the types of receptor mutations which lead to drug resistance and their significance in salvage therapy. Methods: We identified 17 males and 8 female patients with median age 40 yrs (range 9–55 years) with CML who were on imatinib at the time of loss of hematologic response (HR), cytogenetic (CyR), or molecular response (MR) and performed imatinib-resistance mutation analysis. The sequencing was done on ABI machine by direct sequencing method. Results: This group included 22 patients with chronic phase (CP) disease, 2 patients with accelerated phase (AP), and 1 patient with extramedullary blast crisis (BC). Fourteen patients received treatment with agents other than imatinib as the first-line therapy due to either nonavailability of the drug at the time of diagnosis in India, but were started on imatinib when drug became available. The other 11 patients received imatinib as first-line therapy. The best response to imatinib included major CyR in 14 patients which included 3 patients with complete CyR and minor CyR in 6 patients. Lack of HR was noted in 2 patients in whom CyR was not evaluated. Imatinib resistance mutation analysis was prompted by no HR (n = 2); loss of HR after achieving CyR (n = 9); failure to achieve CyR milestones (n = 3); loss of CyR (n = 9); development of extramedullary BC (n = 1). The analysis revealed no mutations-11 patients, M351T-4 patients, G250E-3 patients, F317L-2 patients, M244V- 1 patient, T315I-1 patient, F382L-1 patient, results awaited in 4 patients with 2 patients showing 2 mutations. Conclusions: The majority of patients 11/25 had no detectable mutations while T315I which confers resistance to all TKIs was detected only in 1/25 patients who demonstrated loss of response in our population. The correlation of the other mutations to loss of response and the response to second line TKI needs to be studied in further detail. In addition analysis of mutation patterns at baseline may help in stratifying patients for treatment. No significant financial relationships to disclose.

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Clinical management of lung adenocarcinoma patients with HER2 V659E mutation.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21521 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21521-e21521

Author(s):

Ziqi Jia ◽

Naixin Liang ◽

Yadong Wang ◽

Yanyu Wang ◽

Junyi Ye ◽

...

Keyword(s):

Molecular Docking ◽

Lung Adenocarcinoma ◽

Clinical Management ◽

Transmembrane Domain ◽

Covalent Binding ◽

Docking Simulation ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Covalent Inhibitors

e21521 Background: ERBB2 mutations, mostly affecting the kinase domain (KD), were later found in the transmembrane domain (TMD), most frequently seen in residues V659, G660, but with a much lower prevalence. Comparing to other solid tumors, ERBB2-mutant NSCLC shows a lower response rate to HER2 inhibitors (HER2i). ERBB2 V659E has been reported to respond to lapatinib in combination with carpecitabine, afatinib, or ado-trastuzumab emtansine (TDM-1). However, since the prevalence of ERBB2 V659E is low, no study has reported the subsequent clinical management after developing resistance to HER2i. Methods: We retrospectively screened genomic profiles of 7,812 lung adenocarcinoma (LADC) patients. Molecular docking of lapatinib, afatinib and pyrotinib with the HER2 KD was simulated with AutoDock 4.2 and the binding affinity was predicted by MMPBSA.py program in AmberTools18. Results: We analyzed NGS data of 7812 LADC patients and identified 14 patients (0.18%) with HER2 TMD mutation, mostly V659E mutation (11/7812, 0.14%); other mutations included V664F, T652M, V664F; each occurred in 1 patient. In this cohort, all adenocarcinomas harbor a dinucleotide missense mutation, including 10 TT→AA and 6 TT→AG (c.1976_1977). T P53 was the most frequently co-mutated gene (n = 4) followed by HER2 (n = 2), NSD1 (n = 2) and RARA (n = 2). Treatment history of 9 advanced LADC patients were collected and analyzed. 3 of them had chemotherapy as first-line therapy. 5 patients were treated with HERi as first-line therapy, achieving a median PFS of 192 days (ranged from 60-515days), comparing to patients treated with chemotherapy (71.7±53.3days). 1 patient who was treated with different HERi sequentially in the order of lapatinib, afatinib, TDM-1, achieving an overall PFS of 515 days. Subsequently, she was treated with pyrotinib and had a PFS of 92 days. Molecular docking simulation showed the covalent inhibitors Afatinib and Pyrotinib are more favorable for blocking HER2 KD than non-covalent inhibitor Lapatinib. Between the two covalent inhibitors, Pyrotinib (∆GPyrotinib = -65.92kcal/mol) shows stronger non-covalent binding ability than Afatinib (∆GAfatinib = -59.71 kcal/mol) (p < 0.001). Conclusions: To the best of our knowledge, this is the largest-reported HER2 V659E mutation cohort. We revealed the prevalence of ERBB2 V659E in Chinese LUAD patients and elucidated the genomic profile of ERBB2 V659E mutant. This study paves avenue for the utilization of the novel HER2 inhibitors pyrotinib in ERBB2 V659E mutant LUAD patients.

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Clinical option of pemetrexed-based versus paclitaxel-based first-line chemotherapeutic regimens in combination with bevacizumab for advanced non-squamous non-small-cell lung cancer and optimal maintenance therapy: evidence from a meta-analysis of randomized control trials

BMC Cancer ◽

10.1186/s12885-021-08136-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Le-Tian Huang ◽

Rui Cao ◽

Yan-Ru Wang ◽

Li Sun ◽

Xiang-Yan Zhang ◽

...

Keyword(s):

Maintenance Treatment ◽

Meta Analysis ◽

Small Cell ◽

The Other ◽

Small Cell Lung ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Oncogenic Driver ◽

Grade 3

Abstract Background In the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy. Methods All eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP ± B) and paclitaxel-carboplatin with bevacizumab (PC + B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem + B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events. Results Data of 3139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP ± B and PC + B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP ± B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC + B (all P < 0.05). PP ± B resulted in higher rates of grade 3/4 anemia and thrombocytopenia, but lower rates of neutropenia, febrile neutropenia, and sensory neuropathy than PC + B (all P < 0.001). The other three RCTs were included in an analysis that compared Pem + B and B as a maintenance treatment. Compared with B, Pem + B maintenance treatment resulted in significant improvements in OS (HR, 0.88), PFS (HR, 0.64), and PFSR1y (RR, 0.70), but higher rates of anemia, thrombocytopenia, and neutropenia (all P < 0.001). Conclusion Although the first-line PP + B regimen had longer PFS and PFSR1y than the PC + B regimen, no OS difference was observed. Addition of pemetrexed to bevacizumab as maintenance therapy significantly improved OS compared with bevacizumab maintenance alone, but led to more toxicity.

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