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For patients with pretreated, advanced non-small cell lung cancer (NSCLC). who do not harbor targetable molecular alterations, erlotinib may have similar efficacy compared with chemotherapy, a study in press for publication in Lung Cancer suggests. 1
Table 4: Selected Adverse Reactions Occurring with an Incidence Rate ≥ 10% and an Increase of ≥ 5% in Tarceva-treated Pancreatic Cancer Patients: 100 mg cohort (Study 2)
The aim of this study was to explore the effects of erlotinib combined with radiation on human nasopharyngeal carcinoma (NPC) radiosensitivity using the CNE1 and CNE2 cell lines. Human NPC cells were treated with erlotinib and/or radiation. The effect of erlotinib on the radiosensitivity of the cells was detected using a clonogenic cell survival assay. The rate of apoptosis and the cell cycle were evaluated using flow cytometry. An NPC xenograft model in NOD-SCID mice was used to evaluate the efficacy of the combination therapy of erlotinib with radiation. Erlotinib enhanced the sensitivity of the CNE1 and CNE2 cells to radiation, with sensitization enhancement ratios (SERs) of 1.076 and 1.109, respectively. Erlotinib combined with radiation induced G2/M phase cell cycle arrest in the two cell lines. The mouse tumor model demonstrated a significant reduction in NPC tumor volume in mice treated with erlotinib in combination with radiation when compared with that in mice treated with radiation alone. Erlotinib combined with radiation provoked G2-M phase cell cycle arrest, thereby enhancing the sensitivity of the NPC cells to radiation.
Ongoing phase II and III studies employing erlotinib in the treatment of NSCLC
Gefitinib, an oral small molecule agent that inhibits epidermal growth factor receptor (EGFR) tyrosine phosphorylation (1 ), is the first targeted agent to be approved for the treatment of the patients with advanced non-small cell lung cancer (NSCLC), which has demonstrated clinical efficacy in the second or third-line treatment of NSCLC, especially among never-smokers, females, East Asians, and patients with adenocarcinoma (2 ,3 ). Erlotinib, another EGFR-TKI, also has shown a survival benefit in second-line or third-line treatment for advanced NSCLC (4 ,5 ).
14: Shi L, Tang J, Tong L, Liu Z. Risk of interstitial lung disease with gefitinib and erlotinib in advanced non-small cell lung cancer: a systematic review and meta-analysis of clinical trials. Lung Cancer. 2014 Feb;83(2):231-9. doi: 10.1016/j.lungcan.2013.11.016. Epub 2013 Nov 27. Review. PubMed PMID: 24332320.
The primary endpoint of our study was OS which was defined as the period from definite disease progression before erlotinib or BSC alone until the date of death or final follow-up. Time to progression (TTP) of the erlotinib group was measured from the first day of erlotinib treatment until the first objective or clinical sign of disease progression or death. Tumor response evaluation was performed by computed tomography scan 4 weeks after commencement of gefitinib or erlotinib treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) Committee, and then every 8 weeks. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Survival curves were estimated by the Kaplan–Meier method 21 and compared by means of the log–rank test. 22 Patients’ characteristics before erlotinib treatment or BSC were analyzed in univariate and multivariate Cox proportional hazard regression models. 23 Comparison of the qualitative data was done by Pearson χ 2 or the Fisher exact test. Statistical significance was assumed at a P -value of 0.05 or less.
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FA Shepherd. K Ding. A Sakurada. etal: Updated molecular analyses of exons 19 and 21 of the epidermal growth factor receptor (Egfr) gene and codons 12 and 13 of the kras gene in non-small cell lung cancer (NSCLC) patients treated with erlotinib in National Cancer Institute of Cancer J Clin Oncol 25: 402s. 2007 suppl abstr 7571
These highlights do not include all the information needed to use TARCEVA safely and effectively. See full prescribing information for TARCEVA. TARCEVA (erlotinib hydrochloride) tablet for oral use Initial U.S. Approval: 2004
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Erlotinib Hydrochloride Tablets, 25 mg, 100 mg and 150 mg, had U.S. sales of approximately $638.7 million for the 12 months ending March 31, 2013, according to IMS Health.
Erlotinib Hydrochloride Selective EGFR inhibitor
U.S. Patent No. 7,625,911 ("the '911 patent") discloses a process for preparing amorphous form of erlotinib hydrochloride by dissolving crystalline erlotinib hydrochloride in methanol, ethanol or a mixture of ethanol and water to complete dissolution followed by removal of the solvent from the reaction mixture using distillation or spray drying.
Interestingly, the 4-amino-quinazoline motif interacts with BRD4 Asn 140 and the EGFR hinge region, thereby rationalizing its dual activity. 2870 binds EGFR with an IC 50 of 0.044 μ M as compared to 9.02 μ M for BRD4. This difference in binding affinity can be rationalized based on the trajectories obtained from the MD simulations of 2870 for each target. The molecular interactions analyzed in the MD simulations suggest possible positions for chemical optimization of 2870 to develop derivatives with more equal BRD4 and EGFR potency, which would likely increase compound efficacy. These include the alkoxy residues and the 4-alkyl-/aryl-amino substituents. Although the 4-amino-quanzoline is a well-known EGFR scaffold, all drugs have a 4-aryl substituent, in contrast to 2870, which is alkyl-amino substituted (2-fluorophenoxy-2-ethyl-amino). This allows more flexibility, but still enables the formation of aromatic interactions in the kinase binding site, and may explain its dual EGFR-BRD4 activity. This significant difference is also reflected in its low Tanimoto similarity to known EGFR kinase drugs. Among known EGFR inhibitors, 2870 is least dissimilar to Erlotinib (0.446), compared to Lapatinib (0.389), Gefitinib (0.261), and AEE788 (0.239). 2870 shares even less chemical similarity to any known BRD4(1) binder with the closest compound being 0.3 similar. 2870 can therefore be considered a novel multi-target inhibitor with respect to both BRD4 and EGFR.
[0042] The term "erlotinib or pharmaceutically acceptable acid addition salts of erlotinib substantially free of N-methoxyethyl impurity" refers to the erlotinib or pharmaceutically acceptable acid addition salts of erlotinib having the content of N-methoxyethyl impurity in less than about 0.1% by weight, preferably less than about 0.05% by weight and still more preferably having no traces of the N-methoxyethyl impurity.
This trial, known as BR.21 (BR stands for bronchus in the NCI Canada naming system), randomized 731 patients who had received one or two prior lines of chemotherapy to either tarceva at 150 mg by mouth daily for two thirds of patients, vs. placebo daily for the other third of patients. This showed a significant survival benefit of about two months for the recipients of tarceva, and also an improvement in the likelihood of not progressing at various time points (about 40% improvement compared with placebo). The chance of not progressing at 6 months after starting the trial was more than doubled in patients on tarceva vs. placebo. As with even our best chemo for previously treated NSCLC. tarceva showed a response rate (at least 50% shrinkage of the tumor) of 9%. Side effects were generally modest. While 76% of patients developed a rash, it was severe in less than 10% of patients on tarceva. Diarrhea was also seen in just over half of patients, but this was rarely a significant side effect. Overall, 27% had their drug held for a week or more, 19% of patients had dose reductions due to side effects, and 5% stopped tarceva due to side effects. Also interesting is the fact that 2% of patients found a placebo to be intolerably toxic.
29. The compound as claimed in claim 28, wherein the erlotinib or a pharmaceutically acceptable salt erlotinib is having no traces of the N-methoxyethyl impurity.
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Moore MJ. Goldstein D. Hamm J. et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 ; 25. 1960 - 1966.
Erlotinib Imp.2
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Gatzemeier U, Pluzanska A, Szczesna A, et al. Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC). J Clin Oncol ASCO Annual Meeting Proceedings (Post Meeting Edition) 2004 ; 22. 7010.
The failure of the first-line combination trials was postulated to be a result of EGFR– TKIs being antagonistic with chemotherapy by arresting the cell cycle; however, the sequential administration of erlotinib and chemotherapy might be superior to chemotherapy alone. 56. 57 The phase 2 FAST–ACT trial (First-Line Asian Sequential Tarceva plus Chemotherapy Trial) examined an alternative treatment sequence; 154 patients (94% Asian) received a gemcitabine-platinum doublet for a maximum of six weeks with subsequent randomization to erlotinib or placebo, combined with chemotherapy, on days 15 and 28 of each four-week chemotherapy cycle. 58 The responding patients continued to receive erlotinib or placebo until disease progression. The median progression-free survival was significantly improved in the erlotinib arm (7.2 vs. 5.5 months, HR = 0.57; P = 0.02). It may be that novel dosing schemes, as used in FAST–ACT, might be required.
She started Tarceva yesterday. The oncologist prescribed 150 mg. But since she is 88 years old and weak, she split the pill in half and had only 75 mg. yesterday. She had 100 mg today.
tenho 2 cx de tarceva para vender rs 3.000,00 cada cx fone 62.84435950
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Phase I Study of Erlotinib (Tarceva) in Combination With AT-101 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
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I had 1/2 lung removed and went thru chemo and radiation and then in Dec 07 went on 150 mg of Tarceva, in Dec 08 changed to 100 mg due to rash, cracked finger tips. I have been cancer free since the surgery, still have diarear problems, but I can handle it. Very grateful and blessed to have this med. Have had 3 PET scans since starting and still cancer free.
I also found some other anecdotal evidence for Tarceva and fevers.
In the analysis by stratification factors used in the randomisation, the gain in PFS favouring erlotinib over chemotherapy was particularly large (74% reduction in risk) for patients with very good performance status (ECOG=0). The difference between the treatment arms was not statistically significant for either the ECOG =2 or the mutation Exon 21 subgroups although each trend favoured erlotinib. These subgroups had small patient numbers and likely lacked adequate statistical power.
Tarceva causing Jaundice.
An Introduction to Tarceva Side Effects
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Lung Neoplasms Erlotinib Gefitinib Epidermal growth factor receptor genes
In the TArceva Italian Lung Optimization tRial (TAILOR), Italian investigators led by Massimo Broggini (Istituto di Ricerche Farmacologiche Mario Negri, Milan) compared erlotinib with chemotherapy as second-line treatment for metastatic NSCLC.
The findings thus far suggest that "adjuvant erlotinib has, at least, a cytostatic effect on micrometastatic disease," the investigators wrote.
21. The process as claimed in claim 1. wherein the process of the invention is carried out by dissolving or suspending crude erlotinib pharmaceutically acceptable acid addition salt in a solvent medium comprising dimethylsulfoxide and an alcoholic solvent, and isolating erlotinib pharmaceutically acceptable acid addition salt substantially free of N- methoxyethyl impurity.
To understand whether sensitivity to erlotinib and expression of EMT genes is mediated by similar mechanisms in pancreatic cancers, as in NSCLC, ZEB1 protein expression was also evaluated in the PDAC cell lines. We hypothesised that ZEB1 gene expression would be reduced in the erlotinib-sensitive cell lines (Aspc-1 and Bxpc-3) compared with the erlotinib-resistant lines (MiaPaCa and Panc-1). ZEB1 mRNA was highly expressed in three of the four lines, but was not significantly expressed in Bxpc-3 cells ( Figure 3B ). ZEB1 protein expression correlated with gene expression data in three of four cell lines. Importantly, in erlotinib-sensitive pancreatic cancer lines, ZEB1 protein levels were reduced ( Figure 3C ). These data indicate that miRNAs can inhibit translation or promote message degradation, and ZEB1 mRNA expression alone is not a reliable surrogate for ZEB1 protein levels. Figure 3D illustrates expression levels of the 13 signature miRNA genes demonstrating that erlotinib-sensitive pancreatic cancer cell lines have high expression of the mir-200 family similar to the NSCLC-sensitive cells.
Erlonat is used in combination with for the treatment of pancreatic cancer