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Researchers at UCLA’s Jonsson Center, led by Dr. Steven Dubinett, have discovered biomarkers capable of predicting the response to a combination treatment by Celebrex and Tarceva by patients with advanced non-small cell lung cancer.
An erlotinib resistant subline (H1650-ER1) was generated upon continuous exposure of NSCLC cell line NCI-H1650 to erlotinib. Cancer stem cell like traits including expression of stem cell markers, enhanced ability to self-renew and differentiate, and increased tumorigenicity in vitro were assessed in erlotinib resistant H1650-ER1 cells.
The metabolism of Erlotinib can be decreased when combined with Lovastatin.
Gefitinib and erlotinib are potent EGFR TKIs, with antitumor activity. In this randomized, single-center, non-comparative phase II trial, the efficacy and safety of gefitinib and erlotinib was evaluated as the second-line therapy for advanced non-small cell lung cancer (NSCLC).
BACKGROUND OF THE INVENTION U.S. Patent No. 5,747,498 disclosed 4-(substituted phenylamino) quinazoline derivatives, processes for their preparation, pharmaceutical compositions in which they are present and method of use thereof. These compounds are Tyrosine Kinase Inhibitors and are useful in the treatment of hyperproliferative diseases, such as cancers, in mammals. Among them, erlotinib hydrochloride, chemically N-(3-ethynylphenyl)-6,7-bis(2-methoxy ethoxy)-4-quinazolinamine hydrochloride is a selective inhibitor of the erbB family of oncogenic and protooncogenic protein tyrosine kinases, such as epidermal growth factor receptor (EGFR), and is useful for the treatment of proliferative disorders, such as cancers, particularly non small cell lung cancer, pancreatic cancer, ovarian cancer, breast cancer, glioma, head cancer or neck cancer. Erlotinib is represented by the following structure:
Here is a collection of user reviews for the medication Tarceva sorted by most helpful.
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The metabolism of Erlotinib can be decreased when combined with Clozapine.
Dacomitinib was compared to erlotinib as second-line treatment of unselected NSCLC patients in this 1:1 randomized open-label study. Stratification factors for the randomization included race (Asian versus non-Asian), smoking status (never-smoker versus ever-smoker), and histology (adenocarcinoma versus nonadenocarcinoma). The primary end point of the trial was ≥45% improvement in median PFS with dacomitinib over erlotinib. 26
non-randomized open-label uncontrolled phase II trial erlotinib 150mg qd until disease progression or unacceptable toxicity
During the study, 24 female BALB/c nude mice were inoculated and dosed by gavage at 12.5 mg/kg erlotinib in 4% SBE-β-CD Captisol ® solution when the tumor size reached 0.95–1.00 cm 3. Blood samples were collected at 0, 0.5, 1, 3, 5, 7, 16, and 24 h (3 mice per time point) after dose, and the plasma layer was obtained by centrifugation at 1500× g for 15 min and stored at -20 °C until analysis. A two-compartment model with a first order absorption was applied to calculate the pharmacokinetics of erlotinib. According to the model, the clearance rate (Cl/F) was 0.739 L·kg −1 ·h −1 (RSE=13.3%), the absorption rate constant (K a ) was 0.952 h −1 (RSE=4.66%), the inter-compartment clearance (Q/F) was 0.0308 L·kg −1 ·h −1 (RSE=40.3%) and the apparent volume of the central and the peripheral compartment were 0.817 L/kg (RSE=13.0%) and 0.152 L/kg (RSE=18.4%), respectively.
To estimate the overall survival in patients with advanced hepatocellular carcinoma treated with bevacizumab and erlotinib hydrochloride vs sorafenib tosylate.
www.ladies-news.ru/index.php/forum/obsuz...74218-erlotinib-2015
Drug interactions with butalbital-acetaminophen-caff oral and erlotinib oral
Als u zwanger wordt tijdens de behandeling met Tarceva, vertel dit dan direct aan uw arts die dan
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Tarceva is prescribed for patients with metastatic non-small cell lung cancer (NSCLC) whose cancer has been identified to have certain Epidermal Growth Factor Receptor (EGFR) mutations by an FDA-approved test (first-line treatment).
souzsadovodov.su/forum/razdel-predlozhen...03-48-tarceva-200-mg
Table 3. Selected adverse events of gemcitabine/erlotinib treatment for advanced pancreatic cancer.
May, 2012 sales of Tarceva in the US have been reported to be around $564.2 million.
3. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol . 2011;12(:735-742.
All of the EGFR-TKIs discussed here undergo faecal excretion. For gefitinib, 86% of unchanged drug and metabolites is excreted in the faeces, with a minor proportion excreted in the bile [61]. Urinary recovery of unchanged drug accounts for <0.5% of the oral doses [50] and [73]. Similarly, less than 10% of the erlotinib dose is recovered in the urine, with <1% excreted as parent drug [69]. The irreversible ErbB family blockers show a similar excretion profile, with faecal excretion of the unchanged parent drug accounting for 85% (afatinib) and 79% (dacomitinib) of the dose [63] and [66]. Renal elimination is responsible for <5% of the administered dose [63] and [66] .
"Smar" targeted photosensitizer conjugated with small molecule target-based anticancer drug which has a simple chemical structure and high stability, is a new promising targeted therapeutic strategy. We herein extended this strategy and reported a novel series of zinc(II) phthalocyanine-erlotinib analogue conjugates with different peripheral substituted positions and lengths of the linker. Having erlotinib analogue as the targeting moiety, all conjugates exhibited high specificity and potent affinity to HepG2 cancer cells and kept high photodynamic activity (IC 50 =3.7–16.7 nmol/L). Structure-activity relationships of these conjugates were assessed by investigating their photophysical/photochemical properties, targeting intracellular uptake and in vitro phototoxicity. The results suggested that α -substituted conjugates showed slightly higher photodynamic activity than β -substituted ones. In conclusion, we have developed a series of promising anticancer agents with high tumor selectivity and anticancer activity for targeted photodynamic therapy.
www.viveramebel.ru/forum/boltalka/8507-p...ls-with-tarceva.html
Didesmethyl Erlotinib CAS No. 183320-12-9 C21H23N3O4 M.W. 381.44 CSTE289
Only minimal published data are available regarding the clinical activity of one EGFR TKI administered after the failure of another. 30 ,31 Govindan et al 31 reported that erlotinib is not effective in patients progressing while receiving gefitinib. It should be noted, however, that all five cases in their report may have had an activating EGFR mutation because they had hallmarks associated with such mutations, such as female sex and/or never-smoker status. 41 As the authors pointed out, they may have ceased responding because of the development of a resistance mutation, and therefore could not be expected to respond to erlotinib. Consistent with this assumption, none of the six patients who initially responded to gefitinib showed responses to erlotinib in our study.
Winer E. Cobleigh M, Dickler M, Miller K, Fehrenbacher L, Jones C & Justice R 2002 Phase II multicenter study to evaluate the efficacy and safety of Tarceva (erlotinib, OSI- 774) in women with previously treated locally advanced or metastatic breast cancer. Breast Cancer Research and Treatment 76 Abstract 445.
There were no relationships between erlotinib PK parameters reflecting drug exposure and clinical activity in this study, which is not surprising. Indeed, the large intrapatient variability of the erlotinib PK observed in this and other studies, as well as the relatively small size of the trial, may have contributed negatively, in part, to this observation ( Soulieres et al . 2004 ; Herbst et al . 2005 ; Perez-Soler and Van Cutsem, 2007 ). The lack of relationships between PK parameters of drug exposure with toxicity and clinical activity also underscores the importance of tumour biology and host features relative to dose and drug exposure in the development of toxicity and clinical benefit in this disease setting. Similarly, no relationship between the PK parameters of OSI-420, the main active metabolite of erlotinib and clinical activity were observed.
Response to erlotinib after failure of gefitinib in a patient with advanced non-small-cell lung cancer
Erlotinib is a small-molecule EGFR-specific tyrosine kinase inhibitor that has shown clinical activity in patients with NSCLC. In a multicenter phase II study, single-agent erlotinib has 14.3% objective response and 28.6% stable disease among 46 patients with recurrent NSCLC. 9 In a large randomized, placebo-controlled trial, single-agent erlotinib prolonged survival compare with placebo in previously treated NSCLC patients. 10 Despite these advances, the activity of erlotinib is confined to a selective group of patients with NSCLC and two large randomized trials of combination of erlotinib with standard chemotherapy as first-line treatment has so far failed to improve the outcome. 11  and 12
In the monotherapy RP2D cohort, the median administered dose was ficlatuzumab 20   mg   kg –1 (range, 16–21), with a median duration of 8.1 weeks (range, 2–102). In the erlotinib combination cohort, patients received median doses of ficlatuzumab 20.0   mg   kg –1 and erlotinib 150   mg   day –1 ; 11 of 13 combination patients had 90 % relative dose intensity. The median treatment duration in the combination cohort was 4 weeks. Of the patients who withdrew from the study, the most common reasons were disease progression (monotherapy RP2D, n = 8; erlotinib combination, n = and treatment failure (monotherapy RP2D, n = 5; erlotinib combination, n = 3). Patient disposition and treatment for all solid tumour cohorts are summarised in Supplementary Table A6 .
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To investigate the tolerability and safety of erlotinib in patients, who can not receive chemotherapy, by registration of side-effects. [ Time Frame: 2010 ] [ Designated as safety issue: No ]
Addition of bevacizumab to erlotinib does not improve survival in patients with recurrent or refractory NSCLC.
Ramalingam SS, Blackhall F, Krzakowski M, et al. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol . 2012;30:3337–3344.
with erlotinib: quality of life analysis of the National Cancer Institute of Canada Clinical
The PBAC also considered that erlotinib and afatinib were relevant comparators.
www.cpja.org.uk/forum/viewtopic.php?f=9&t=1797405
Los pacientes no comunicaron trastornos en el crecimiento ni en la calidad del pelo. El único paciente que no presentó efectos adversos relacionados con el consumo de erlotinib desarrolló metástasis cutáneas del carcinoma epidermoide de pulmón, detectadas por el dermatólogo tras 8 semanas de tratamiento.
Pre-treatment with the CYP3A4 inducer rifampicin for 7 days prior to TARCEVA 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. In a separate study, treatment with rifampicin for 11 days, with co-administration of a single 450 mg dose of TARCEVA on day 8 resulted in a mean erlotinib exposure (AUC) that was 57.6% of that observed following a single 150 mg TARCEVA dose in the absence of rifampicin treatment [see Dose Modifications (2.3 )]. Use of alternative treatments lacking CYP3A4 inducing activity is strongly recommended. If an alternative treatment is unavailable, adjusting the starting dose should be considered. 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 Dosage and Administration (2.3 )].
Erlotinib induces cell cycle arrest but neither immediate cytotoxicity nor apoptosis in esophageal cancer cells
I saw the University of Arizona clinical trial of Avastin/Tarceva and says that this combination has synergistic effect. While Avastin is an antiangiogenesis drug (meaning it stops pathways from feeding tumors) Erlotinib(Tarceva) is an EGFR (Epidermal Growth Factor Inhibitor) receptor inhibitor. EGFR is activated in approx. 30% of all solid tumors. Tarceva alone had a clinical trial on OvCa in 2001 and it had a 59% positive response rate (partial plus stabilization).
Do you take Tarceva and Omeprazole?
Positives CHMP-Votum für Erlotinib in der Erstlinientherapie bei Patienten mit EGFR-Mutation