Математичний аналіз і диференціальні рівняння вивчаю САМ

High Quality - Low Cost Anti-Cancer Drugs

*
Chest computed tomography scan showed a mass in the left upper lobe and multiple nodules (A). Twenty-nine days after initiation of gefitinib treatment, diffuse ground glass opacity was observed (. After improvement of gefitinib-induced interstitial lung disease (ILD) (C), erlotinib was initiated, and diffuse ground glass opacity recurred after 282 days of erlotinib treatment (D). After improvement of erlotinib-induced ILD (E), erlotinib was rechallenged with oral glucocorticoid for 258 days without ILD recurrence until death. Tumor growth was suspended more than 60 days after rechallenge of erlotinib (F).
forwardnsk.ru/index.php/forum/razlichnye...tarceva-approval-fda
On the other hand, the differences in efficacy for combinations of erlotinib plus bevacizumab between our study and the clinical trials [12. 13 ] are just like previous reports, that clinical efficacy is lower than that observed in preclinical cancer models [15. 16. 31. 34 ]. One possible explanation is that the efficacy of bevacizumab alone or combined with other agents differs among tumor types, such as transplantable tumors in mice, spontaneous tumors and tumors from patients, which exhibit different degrees of vessel abnormality and levels of VEGF protein [15 ]. An alternate explanation for the variability in treatment efficacy is that vessel normalization by VEGF blockade is limited to a small window in treatment time. The window of normalization in murine models is relatively short and occurs soon after administration of bevacizumab compared with that in humans [29 ], which may explain several paradoxical findings reported recently and suggest that the schedule and dosing of combination therapies warrant considerable attention. For example, bevacizumab and cetuximab (anti-EGFR monoclonal antibody) have shown promising results in clinical trials in NSCLC [35 ]. However, this is at odds with the results of a study which showed that bevacizumab reduced tumor uptake of cetuximab in SUM149 xenografts (a breast cancer xenograft) [16 ]. A bevacizumab/docetaxel combination was more effective than docetaxel alone in reducing breast and prostate cancer cell growth [36 ], but a rapid decrease in the delivery of docetaxel to tumors after bevacizumab therapy was observed in another study [17 ]. Notably, although the erlotinib concentration in the combination group of H157 model with high VEGF levels was much higher than that in the erlotinib only group, no significant difference in intratumoral erlotinib concentration was observed between these two groups in any of the three models. This might be attributed to different blood flow even within the same tumor, because abnormal vessels in tumors result in continuous vessel remodeling, as well as facilitate drug distribution in perfused and leaking vessels [16. 17 ].
3 Pao W. Miller V. Zakowski M et al . EGF receptor gene mutations are common in lung cancers from ‘never smokers’ and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004 ; 101. 13306 – 11.
Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation
Cross-over response to erlotinib of brain metastatic disease from bronchial adenocarcinoma after gefitinib failure, and an unusual rash
We report a case with good response of brain metastases to gefitinib in an EGFR mutated adenocarcinoma of the lung after progression on erlotinib and two times WBRT.
SEOUL, 5 September (ANTARA/PRNewswire-AsiaNet) — Pasien kanker paru-paru stadium lanjut di seluruh dunia kini dapat berharap hidup lebih lama menurut data baru dari TRUST study yang dipaparkan pada Konferensi Kanker Paru-paru tingkat Dunia (WCLC) ke-12 di Seoul, Korea. Observasi baru dari seluruh dunia ini menunjukkan bahwa pasien kanker paru-paru non sel kecil (NSCLC) dan diobati dengan Tarceva (erlotinib) dalam praktek klinik rutin hidup lebih lama. Sejumlah hasil dari TRUST menambah sejumlah manfaat yang pasien alami pada kajian BR. 21yang penting yang membuat Tarceva disetujui di lebih dari 80 negara. Kanker paru-paru non sel kecil merupakan bentuk paling umum dari kanker paru-paru yang diderita oleh lebih dari satu juta orang di seluruh dunia.
Allaitement : on ignore si l'erlotinib passe dans le lait maternel. Si vous prenez ce médicament pendant que vous allaitez, votre bébé pourrait en ressentir les effets. À cause du potentiel de lésion grave pour un bébé s’il est exposé à ce médicament, nous avertissons les femmes qui allaitent leur bébé de ne pas utiliser ce médicament.
gofishtalk.com/profiles/blog/new
To explore the activity of CUDC-101 against EGFR inhibitor-resistant cells, we selected 6 erlotinib-tolerant/resistant (TR) single clones after 2 months of drug exposure and compared their sensitivity with CUDC-101 and EGFR inhibitors. All HCC827-TR clones were no longer sensitive to erlotinib and gefitinib with a 500-fold or greater increase in growth inhibitory IC 50 relative to the parental cell line (Supplementary Table ST1). In contrast, their sensitivity to CUDC-101 did not change significantly. The fact that all HCC827-TR clones remain sensitive to CUDC-101 indicates that CUDC-101 may be able to circumvent common EGFR-inhibitor resistance mechanisms.
www.amanogawa.ru/index.php/forum/obshchi...-erlotinib-vademecum
A recent study directly compared erlotinib with docetaxel and it found erlotinib is less effective at extending progression-free survival in patients whose tumours test negative for the EGFR-TK mutation.
Van Cutsem E, Beale P, Delord J-P, Verslype C, Clarke S, Couteau C, Rakhit A, Fettner S, Brennscheidt U, Feyereislova A (2003) Tarceva™ (erlotinib) in combination with Xeloda ® (capecitabine) and oxaliplatin in patients with metastatic colorectal cancer: a phase I dose-escalation trial. Clin Cancer Res 9 (16 Part 2): 6095S (abstract A109)
Mean plasma concentration–time curves for erlotinib alone and in combination with docetaxel and carboplatin for cohort 1.
Phase 2 Study of Maintenance OSI-906 Plus Erlotinib (Tarceva), or Placebo Plus Erlotinib in Patients With Nonprogression Following 4 Cycles of Platinum-based Chemotherapy - www.ClinicalTrials.gov
Erlotinib received approval from the Food and Drug Administration (FDA) in November 2004 and from the European Medicines Agency in June 2005 as a second- or third-line therapy for patients with locally advanced or metastatic NSCLC. Gefitinib initially received approval by the FDA in 2003. However, on the basis of data from the subsequent ISEL trial, which did not show a survival advantage or an improvement in disease-related symptoms, 15 the labeling of gefitinib was modified to limit its use to patients who are currently benefiting or who have previously benefited from gefitinib therapy. In July 2009, the European Medicines Agency granted approval for the use of gefitinib in any line of therapy for patients with NSCLC who carry activating EGFR mutations. The approval of gefitinib is still restricted in the United States, but as of early 2011, the drug is licensed in 66 countries worldwide (www.iressa.com ).
www.blago-svet.com.ua/index.php?option=c...82&func=post&lang=en
In addition to sample preparation, another focus of bioanalytical method development is chromatographic separation. Hydrophilic interaction liquid chromatography (HILIC) has been increasingly gaining in popularity mainly because it provides good retention for polar analytes. Meanwhile, HILIC columns often allow direct injection of organic extract into the LC-MS/MS system so that the dry-down and reconstitution steps could be eliminated without the compromise of chromatographic peak shape. The above advantages have been demonstrated by several examples [21 ,22 ,23 ,24 ,25 ]. In this manuscript, we delineate an application case of the combination of the automatic 96-well format SLE sample extraction with direct injection of the organic extract into a HILIC-MS/MS, for the simple and fast measurement of erlotinib in human plasma. The features of this novel approach are demonstrated by the assay development and validation of erlotinib in human plasma. The matrix effect, extraction efficiency and recovery of using SLE extraction and HILIC with MS/MS detection are compared with other routine sample preparation approaches.
Rifampin increased erlotinib clearance, resulting in decreased plasma erlotinib concentrations 1
neos76.ru/index.php/component/kunena/6--...tic-cancer.html#2450
miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells
The pharmacokinetics of erlotinib after administration of a single dose in female BALB/c nude mice plasma was determined by a LC-MS/MS method previously described by our group 17. The concentration range was 0.5–200 ng/mL, and samples with concentration greater than 200 ng/mL were diluted until the concentration was within the appropriate range. The intra- and inter-day accuracies ranged from 2.00% to 8.00% and 0.07% to 4.0%, respectively, and the intra- and inter-day precision ranged from 2.28% to 8.22% and 5.66% to 14.12%, respectively; all of these values were within the predefined acceptance criteria. The method also presented good stability of erlotinib in plasma at room temperature for 8 h, at -20 °C for 30 d, and after three daily freeze-thaw cycles. The recoveries were 97.01%±14.97%, 101.92%±10.95% and 93.04%±8.36% for erlotinib, at low, medium and high concentrations, respectively, where no matrix effect was observed.
Pre-treatment with the CYP3A4 inducer rifampicin decreased erlotinib AUC by about 2/3 to 4/5, which is equivalent to a dose of about 30 to 50 mg in NSCLC patients. Use of alternative treatments lacking CYP3A4 inducing activity is strongly recommended. If an alternative treatment is unavailable, adjusting the starting dose should be considered. (see DOSING AND ADMINISTRATION - Dose Modifications section). If the TARCEVA dose is adjusted upward, the dose will need to be reduced immediately to the indicated starting dose upon discontinuation of rifampicin or other inducers. Other CYP3A4 inducers include, but are not limited to, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John's Wort (see CLINICAL PHARMACOLOGY - Interactions and DOSAGE AND ADMINISTRATION - Dose Modifications sections).
Adverse events were observed in animal reproduction studies. Based on the mechanism of action, may cause fetal harm if administered in pregnancy. Females of reproductive potential should be advised to avoid pregnancy; highly effective contraception is recommended during treatment and for at least 2 weeks after the last erlotinib dose.
It is well known that EGFR mutations are associated with sensitivity or resistance to erlotinib. Thus, the EGFR status is a potential strong confounding factor for the analysis of miR-17-5p in erlotinib resistance. In the ideal case, the patients should be stratified according to the EGFR status and the real contribution of miR-17-5p to erlotinib resistance could be investigated. However, it is difficult to perform stratification analysis in small size samples. Thus we investigated wild-type EGFR patients whose erlotinib resistance could not be simply attributed to EGFR mutations. In these patients, miR-17-5p might play an important role in erlotinib resistance.
Experimental: Erlotinib and Chemotherapy
des2pro.ru/forum/dobro-pozhalovat/4490-p...-vand-tarceva-150-mg
Table 1. Comparison of the phase II study results of Tivantinib and MetMab, both of which were studied in combination with erlotinib compared to placebo and erlotinib.
Which begs the all important question – which patients did well on METMab plus erlotinib?
gtpartner.by/index.php/component/kunena/...eva-medication-guide
Enterovirus Infections Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Erlotinib Hydrochloride Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action
Chaft JE, Oxnard GR, Sima CS, Kris MG, Miller VA, Riely GJ. Disease flare after tyrosine kinase inhibitor discontinuation in patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib: implications for clinical trial design. Clin Cancer Res . 2011 Oct 1. 17(19):6298-303. [Medline].
Patients are eligible if they have not had prior exposure to an EGFR inhibitor (e.g.Gefitinib, Erlotinib) or antibody (e.g. Cetuximab).