High Quality - Low Cost Anti-Cancer Drugs
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*
No evidence has been found yet that the treatment with tarceva beyond the progression of disease is beneficial.
The serum concentration of Erlotinib can be decreased when it is combined with Magnesium oxide.
Pregnancy. Tarceva can harm an unborn baby. Women should use effective birth control during treatment and for at least 1 month after the last dose of Tarceva. Tell your HCP if you have become pregnant, or if you think you may be pregnant, during treatment with Tarceva. Do not breast-feed during treatment with Tarceva and for 2 weeks after the final dose.
Continue erlotinib at current dose and monitor for change in severity; continue treatment of rash
Tumor Growth Reduced With Cabozantinib Plus Erlotinib in EGFR-Positive NSCLC
ARM I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
According to another object of the present invention is to provide a novel process for preparing erlotinib hydrochloride crystalline polymorph form A substantially free of polymorph B.
www.blago-svet.com.ua/index.php?option=c...82&func=post&lang=en
Brand Name. Tarceva Active Ingredients. Erlotinib Hydrochloride Manufacturer. Roche Holding AG Strength: 150 mg Form: Tablets Packing: Pack of 30 Tablets
PRODUCT OF NATCO COMPANY - ERLONAT
Cetuximab in Patients With Lung Adenocarcinoma Receiving Erlotinib That Have Developed "Acquired Resistance" to Erlotinib
The paradigm that EGFR mutations confer sensitivity to gefitinib or erlotinib provides no insight into whether these mutations also confer sensitivity to the monoclonal antibody cetuximab, and some data exist to suggest that they will not. Clinical responses to tyrosine kinase inhibitors after failure with cetuximab have been reported (51 ). Mechanistic differences between the two approaches to EGFR inhibition clearly exist (52 ): cetuximab binds to the cell-surface receptor, resulting in internalization and degradation, whereas the kinase inhibitors bind to the intracellular tyrosine kinase domain. Cetuximab may induce antibody-dependent cell-mediated cytotoxicity and thus may be able to target any cell-surface EGFR, whether mutated or not. Simple overepxression could confer sensitivity to cetuximab but not to the tyrosine kinase inhibitor. Treatment with gefitinib, erlotinib, or the anti-EGFR antibody cetuximab induced apoptosis in HCC827, a NSCLC cell line with EGFR gene amplification and exon 19 deletion (30 ). However, in other EGFR-mutant cell lines, cetuximab had relatively little effect (53 ). Intriguingly, in the gefitinib-insensitive H1975 cell line, which harbors two mutations (L858R and T790M), a dose-dependent induction of apoptosis was observed with cetuximab (47 ). This resistance-inducing secondary T790M EGFR mutation has been observed in half of drug-resistant NSCLCs, making the observation with cetuximab of particular relevance (11. 54. 55 ). Cetuximab also induced apoptosis in the EGFR-wild-type cell line expressing K-ras mutations (Hop18; ref. 47 ). Whereas the role of cetuximab in NSCLC is still not completely defined, it is well established in colorectal cancer, in which EGFR amplification and the absence of K-ras mutations are associated with cetuximab response (56. 57 ).
Results showed no statistically significant difference in median disease-free survival (50.5 months with erlotinib vs 48.2 months with placebo; HR = 0.90; 95% CI: 0.74, 1.10; P <.001).
To confirm the role of the CIP2A / PP2A / p-Akt pathway in mediating induction of apoptosis of HCC cells by TD52, we generated PCL5 cells with ectopic overexpression of myc-tagged CIP2A by transient transfection ( Figure 2e ). Compared with wild-type cells, the expression level of p-AKT was upregulated in the CIP2A-overexpressing cells. Furthermore, using sub-GI analysis, we found that the apoptotic effect of TD52 was significantly reduced in these CIP2A-overexpressing PLC5 cells. Next, we investigated the role of PP2A in mediating the effects of TD52 on HCC cells by two strategies, knockdown of PP2A by silencing RNA (siRNA), and co-treatment with a PP2A inhibitor, okadaic acid (OA) ( Figures 2f and g ). When PLC5 cells were treated with OA at 100   nM, the expression level of p-Akt was enhanced and TD52-induced HCC tumor cell apoptosis was reduced ( Figure 2f ). Similarly, when PP2A was knocked down by siRNA of PP2A, expression of p-Akt was increased and the antitumor effects of TD52 were reversed. In previous studies, we found that Akt serves as an important downstream effector of PP2A in erlotinib treatment. Therefore, we further generated Akt-overexpressing PLC5 cells by transient transfection and found that TD52-induced apoptosis of HCC cells was significantly reduced ( Figure 2h ). The results of PP2A inhibition and ectopic overexpression of CIP2A and Akt thus validated the critical role of the CIP2A / PP2A / p-Akt signaling pathway in mediating the effect of TD52 in HCC cells.
autoamalgama.ru/forum/zadajte-vopros/313...how-is-tarceva-given
Comparison of Gefitinib and Erlotinib for Patients with Advanced Non-Small-Cell Lung Cancer Lee, Jin Hwa; Lee, Kyoung Eun; Ryu, Yon Ju; Chun, Eun Mi; Chang, Jung Hyun;
28 Tabla 6: Resultados de eficacia (TR, SLP y SG) de cada uno de los estudios Estudio Grupo de tratamiento RC + RP (%) SLP (meses) SG (meses) IPASS Mok T, et al. FIRST-SIGNAL Lee SM, et al. Maemondo M, et al. Gefitinib 250 mg/día 71,2 9,5 21,6 Paclitaxel 200 mg/m 2 + carboplatino (AUC=5-6), ambos día 1, ciclos de 21 días x 6 ciclos 47,3 6,3 21,9 Gefitinib 250 mg/día 84,6 8,4 30,6 Gemcitabina mg/m 2 días 1 y 8 + cisplatino 80 mg/m 2 día 1, ciclos de 21 días x 9 ciclos 37,5 6,7 26,5 Gefitinib 250 mg/día 73,7 10,8 30,5 Paclitaxel 200 mg/m 2 + carboplatino (AUC=6), ambos día 1, ciclos de 21 días, más de 3 ciclos 30,7 5,4 23,6 Gefitinib 250 mg/día 62,1 9,2 30,9 Mitsudomi T, et al. Docetaxel 60 mg/m 2 + cisplatino 80 mg/m 2, ambos día 1, ciclos de 21 días, de 3 a 6 ciclos OPTIMAL Zhou C, et al EURTAC Rossel R, et al. 32,2 6,3 ND Erlotinib 150 mg/día 83,0 13,1 ND Gemcitabina mg/m 2 días 1 y 8 + carboplatino (AUC = 5) día 1, ciclos de 21 días, x 4 ciclos 36,0 4,6 ND Erlotinib 150 mg/día 55,0 9,4 18,9 Doblete con quimioterapia estándar basada en platino* * Opciones de doblete con quimioterapia estándar basada en platino: - gemcitabina mg/m 2 días 1 y 8 + cisplatino 75 mg/m 2, día 1 - docetaxel 75 mg/m 2 día 1 + cisplatino 75 mg/m 2, día 1 - docetaxel 75 mg/m 2 día 1 + carboplatino (AUC = 6) día 1 - gemcitabina mg/m 2 días 1 y 8 + carboplatino (AUC = 5) día 1 AUC = área bajo la curva ND = datos no disponibles RC = respuesta completa RP = respuesta parcial SLP = supervivencia libre de progresión SG = supervivencia global 11,0 5,2 14,4 En las Tablas 4 y 5 se indican las principales características de los ECAs de gefitinib y erlotinib frente a quimioterapia, en pacientes previamente no tratados con CPNM avanzado o metastásico, con mutación activadora EGFR. En la Tabla 6 se indican los resultados de eficacia de cada uno de los estudios incluidos en la RS. < 26 >
What Went Wrong? Failure of MetMab with Tarceva in Advanced 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:
Erlotinib (Tarceva) package insert (locally hosted backup). Original source: www.gene.com/gene/products/information/p...ceva-prescribing.pdf, accessed 5/14/2013.
Stop taking erlotinib and call your doctor at once if you have a serious side effect such as:
The PBAC noted that the key EURTAC trial in mutation positive patients suggested a statistically significant and potentially clinically important benefit for erlotinib monotherapy over platinum-based chemotherapy in terms of an additional median progression-free survival of approximately 4.5 months (log rank p < 0.0001, 26 January 2011 cut-off) compared to platinum chemotherapy. Because the EURTAC trial allowed for switching (cross-over) on disease progression, the results for overall survival inform a comparison of early versus late erlotinib; and they currently show no benefit (as at 26 January 2011 cut-off, log rank p = 0.8702). The PBAC noted that the comparison of early versus late erlotinib is relevant in the Australian context because erlotinib is currently listed second-line in unselected patients. Thus the clinical benefit for EGFR activating mutation positive patients of listing erlotinib as first-line treatment in addition to second-line treatment is an improvement in quality of life, but not a prolongation of life.
microgorod24.ru/forum/ochered-1/656-post...17-erlotinib-tribute
No clinically relevant interaction of bevacizumab was observed on the pharmacokinetics of co-administered interferon alpha 2a, erlotinib (and its active metabolite OSI-420), or the chemotherapies irinotecan (and its active metabolite SN38), capecitabine, oxaliplatin (as determined by measurement of free and total platinum), and cisplatin. Conclusions on the impact of bevacizumab on gemcitabine pharmacokinetics cannot be drawn.
Patient characteristics. After a review of EGFR genotyped patients in our centers from 2004 to 2008, we identified 18 EGFR mutated patients that had received gefitinib and erlotinib. Clinical, demographic, pathologic, and molecular characteristics of this cohort are displayed in Table 1. Sixty-one percent of patients were women (11 of 18) and the majority never smokers (11 of 18). Ages varied between 43 and 80 years (Table 1 ). Almost all (16 of 18) patients had adenocarcinoma as the main histologic type of their tumor. These characteristics are similar to historic cohorts of EGFR mutated tumors (17 ). Exon 19 deletion-containing tumors were found in 13 (72%) patients, L858R mutations in 4 (22%) patients, and L861Q in 1 patient (Table 1 ).
"ASPIRATION supports the efficacy of first-line erlotinib therapy in patients with EGFR mutation-positive NSCLC and that treatment beyond progression is feasible and may delay salvage therapy in selected patients," the authors write.
Treatment with TKI and chemotherapy was well tolerated. TKI-patients had a significantly longer OS from progression on TKI (case–control: median 14.5 vs. 2.0 months, HR 0.154) and longer OS from diagnosis of lung cancer (case–control: median 54.5 vs. 28.3 months, HR 0.474). An activating EGFR mutation was detected in 13 of the 23 patient tested (57%). Both among patients with and without detection of an activating EGFR mutation, those treated with erlotinib beyond progression had a longer survival.
Pancreatic Cancer Bevacizumab Avastin™ Anti-VEGF monoclonal antibody rhuMAb-VEGF Erlotinib
“We used a matched-pair design to maximize the reduction of potential bias due to the retrospective nature of study, although the results regarding differences in side effects between the two drugs were not fully determined in this study,” said lead author Myung-Ju Ahn, MD . of Samsung Medical Center, Sungkyunkwan University School of Medicine. Seoul, South Korea. “Based on these results, both gefitinib and erlotinib can be recommended for the treatment of patients with EGFR -mutant NSCLC.”
tsariki.ru/forum/vakansii-v-rajone-tsari...6-16-46-erlonat-wiki
Drug: Vinorelbine (Navelbine) Drug: Erlotinib
Erlotinib in Treating Patients With Solid Tumors and Liver or Kidney Dysfunction
stom05.ru/kunena/reklamnyj-razdel/3003-p...harmacokinetics.html
This labeling supplement is based on the results of the IUNO trial, a randomized, double-blind, placebo-controlled study of erlotinib administered as maintenance therapy in 643 patients with advanced NSCLC who had not experienced disease progression or unacceptable toxicity during four cycles of platinum-based first-line chemotherapy. Patients whose tumors harbored activating EGFR mutations (exon 19 deletions or exon 21 L858R mutations) were excluded from the study. Participants were randomly assigned to receive erlotinib (n = 322) or placebo (n = 321) orally once daily until disease progression or unacceptable toxicity occurred. After progression on initial therapy, the patients were eligible to enter an open-label phase. Fifty percent of patients treated with erlotinib entered the open-label phase and received chemotherapy, while 77% of patients given placebo entered the open-label phase and received erlotinib.
Establishment of an erlotinib-resistant cell line
23 Rudin CM. Liu W. Desai A. et al. Pharmacogenomic and pharmacokinetic determinants of erlotinib toxicity. J Clin Oncol. 2008 ; 26. 1119 - 1127.
Erlotinib metabolism and drug adjustments
Sales of the best Erlotinib hydrochloride /OSI-774/cas: 183319-69-9
Erlotinib is in Pregnancy Category D. Both breast-feeding and pregnancy should be avoided in patients receiving erlotinib. 4
Motesanib + Gemcitabine + Erlotinib
www.clubmycity.ru/forum/2-dobro-pozhalov...nd-coughing-up-blood
Neither erlotinib (small decrease) nor bevacizumab (small increase) administered alone had a significant impact on tumour cell proliferation ( P >0.05 vs controls) ( Figure 3 ). In contrast, RT application induced cell proliferation ( P = 0.007 vs controls). This RT-related effect on tumour cell proliferation was diminished by the presence of erlotinib + bevacizumab to a level similar to the controls ( P = 0.0037 vs RT; P = 0.587 vs controls).
Erlotinib was kindly provided by Roche (Neuilly sur Seine, France) and bevacizumab by our institution's pharmacy. Working solutions were prepared as follows: erlotinib (7.5   g   l −1 ) was suspended in 0.9 % NaCl and 0.01 % Tween 80, and bevacizumab (750   mg   l −1 ) was diluted in 0.9 % NaCl. For both drugs, the concentrations were adjusted so as to include the daily dose in 0.2   ml of drug suspension. Dulbecco's modified Eagle's medium (DMEM), penicillin, streptomycin and glutamine were purchased from Whittaker (Verviers, Belgium). Fetal bovine serum (FBS) was obtained from Dutscher (Brumath, France).
Patients were treated preoperatively with erlotinib (150 mg once daily for 3 weeks) up to 48 hours before surgery. Plasma samples were collected during treatment. Surgical resection involved radical resection of the lung tumor and tumor biopsies were frozen directly after surgery. Erlotinib and O-desmethyl erlotinib concentrations in lung tumor tissue and predose plasma were determined using high performance liquid chromatography coupled with tandem mass spectrometry.
creativemanufacturing.net/profiles/blogs...13-00-erlotinib-drug
A 66-year-old African-American man presented to the emergency department with dyspnea and dry cough. He had an oxygen saturation of 83% on room air. Four months before presentation, the patient was diagnosed with metastatic non-small cell lung cancer (NSCLC). The patient was started on 150 mg of erlotinib daily, five days before presentation after failure of carboplatin and paclitaxel chemotherapy three months earlier. Two days before presentation, a dry cough and a low-grade fever were reported by the patient. He experienced worsening of the cough and dyspnea. The patient was an ex-smoker. Physical examination revealed a temperature of 37.7°C, a blood pressure of 127/65 mmHg, a respiratory rate of 24 breaths/min and a heart rate of 88 beats/min. Chest auscultation was significant for bilateral diffuse crackles, and jugular venous distention was not present. A chest radiograph showed bilateral alveolar-patterned lung opacifications ( Figure 1A ). An echocardiogram showed normal left ventricular systolic and diastolic functions and a computed tomography (CT) scan of the chest showed bilateral ground-glass infiltrates ( Figure 2A ). Pulmonary embolism was not seen on a CT angiogram of the chest. The patient developed respiratory failure and subsequently intubation and mechanical ventilation became necessary. Bronchoscopy showed no evidence of diffuse alveolar hemorrhage (DAH). Bronchoalveolar lavage (BAL) cultures were negative for bacterial, viral, Legionella . Mycobacterium and fungal pathogens. BAL total cell count was 117×10 5 cells/mL and BAL differential cell count showed 76% neutrophils. Erlotinib-associated acute pneumonitis was diagnosed and 250 mg of methylprednisolone intravenously, every 6 h for three days, was started. Corticosteroid therapy was continued with 60 mg of prednisone daily thereafter. Hypoxemia improved after four days and the patient was extubated. A repeat chest radiograph showed marked reduction of the bilateral lung opacities. Two weeks after presentation, the patient was transferred to a rehabilitation centre on tapering prednisone. He still required supplemental oxygen at rest.
Tarceva (erlotinib) is the first next-generation treatment for non-small cell lung cancer (NSCLC) to win marketing approval and has shown it can help prolong the lives of patients with advanced lung cancer, compared to existing treatments.
Generic Erlotinib Dosage and Administrartion
This appears to be the first adequately powered evaluation of erlotinib/bevacizumab specifically in patients with EGFR mutations.
*
No evidence has been found yet that the treatment with tarceva beyond the progression of disease is beneficial.
The serum concentration of Erlotinib can be decreased when it is combined with Magnesium oxide.
Pregnancy. Tarceva can harm an unborn baby. Women should use effective birth control during treatment and for at least 1 month after the last dose of Tarceva. Tell your HCP if you have become pregnant, or if you think you may be pregnant, during treatment with Tarceva. Do not breast-feed during treatment with Tarceva and for 2 weeks after the final dose.
Continue erlotinib at current dose and monitor for change in severity; continue treatment of rash
Tumor Growth Reduced With Cabozantinib Plus Erlotinib in EGFR-Positive NSCLC
ARM I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
According to another object of the present invention is to provide a novel process for preparing erlotinib hydrochloride crystalline polymorph form A substantially free of polymorph B.
www.blago-svet.com.ua/index.php?option=c...82&func=post&lang=en
Brand Name. Tarceva Active Ingredients. Erlotinib Hydrochloride Manufacturer. Roche Holding AG Strength: 150 mg Form: Tablets Packing: Pack of 30 Tablets
PRODUCT OF NATCO COMPANY - ERLONAT
Cetuximab in Patients With Lung Adenocarcinoma Receiving Erlotinib That Have Developed "Acquired Resistance" to Erlotinib
The paradigm that EGFR mutations confer sensitivity to gefitinib or erlotinib provides no insight into whether these mutations also confer sensitivity to the monoclonal antibody cetuximab, and some data exist to suggest that they will not. Clinical responses to tyrosine kinase inhibitors after failure with cetuximab have been reported (51 ). Mechanistic differences between the two approaches to EGFR inhibition clearly exist (52 ): cetuximab binds to the cell-surface receptor, resulting in internalization and degradation, whereas the kinase inhibitors bind to the intracellular tyrosine kinase domain. Cetuximab may induce antibody-dependent cell-mediated cytotoxicity and thus may be able to target any cell-surface EGFR, whether mutated or not. Simple overepxression could confer sensitivity to cetuximab but not to the tyrosine kinase inhibitor. Treatment with gefitinib, erlotinib, or the anti-EGFR antibody cetuximab induced apoptosis in HCC827, a NSCLC cell line with EGFR gene amplification and exon 19 deletion (30 ). However, in other EGFR-mutant cell lines, cetuximab had relatively little effect (53 ). Intriguingly, in the gefitinib-insensitive H1975 cell line, which harbors two mutations (L858R and T790M), a dose-dependent induction of apoptosis was observed with cetuximab (47 ). This resistance-inducing secondary T790M EGFR mutation has been observed in half of drug-resistant NSCLCs, making the observation with cetuximab of particular relevance (11. 54. 55 ). Cetuximab also induced apoptosis in the EGFR-wild-type cell line expressing K-ras mutations (Hop18; ref. 47 ). Whereas the role of cetuximab in NSCLC is still not completely defined, it is well established in colorectal cancer, in which EGFR amplification and the absence of K-ras mutations are associated with cetuximab response (56. 57 ).
Results showed no statistically significant difference in median disease-free survival (50.5 months with erlotinib vs 48.2 months with placebo; HR = 0.90; 95% CI: 0.74, 1.10; P <.001).
To confirm the role of the CIP2A / PP2A / p-Akt pathway in mediating induction of apoptosis of HCC cells by TD52, we generated PCL5 cells with ectopic overexpression of myc-tagged CIP2A by transient transfection ( Figure 2e ). Compared with wild-type cells, the expression level of p-AKT was upregulated in the CIP2A-overexpressing cells. Furthermore, using sub-GI analysis, we found that the apoptotic effect of TD52 was significantly reduced in these CIP2A-overexpressing PLC5 cells. Next, we investigated the role of PP2A in mediating the effects of TD52 on HCC cells by two strategies, knockdown of PP2A by silencing RNA (siRNA), and co-treatment with a PP2A inhibitor, okadaic acid (OA) ( Figures 2f and g ). When PLC5 cells were treated with OA at 100   nM, the expression level of p-Akt was enhanced and TD52-induced HCC tumor cell apoptosis was reduced ( Figure 2f ). Similarly, when PP2A was knocked down by siRNA of PP2A, expression of p-Akt was increased and the antitumor effects of TD52 were reversed. In previous studies, we found that Akt serves as an important downstream effector of PP2A in erlotinib treatment. Therefore, we further generated Akt-overexpressing PLC5 cells by transient transfection and found that TD52-induced apoptosis of HCC cells was significantly reduced ( Figure 2h ). The results of PP2A inhibition and ectopic overexpression of CIP2A and Akt thus validated the critical role of the CIP2A / PP2A / p-Akt signaling pathway in mediating the effect of TD52 in HCC cells.
autoamalgama.ru/forum/zadajte-vopros/313...how-is-tarceva-given
Comparison of Gefitinib and Erlotinib for Patients with Advanced Non-Small-Cell Lung Cancer Lee, Jin Hwa; Lee, Kyoung Eun; Ryu, Yon Ju; Chun, Eun Mi; Chang, Jung Hyun;
28 Tabla 6: Resultados de eficacia (TR, SLP y SG) de cada uno de los estudios Estudio Grupo de tratamiento RC + RP (%) SLP (meses) SG (meses) IPASS Mok T, et al. FIRST-SIGNAL Lee SM, et al. Maemondo M, et al. Gefitinib 250 mg/día 71,2 9,5 21,6 Paclitaxel 200 mg/m 2 + carboplatino (AUC=5-6), ambos día 1, ciclos de 21 días x 6 ciclos 47,3 6,3 21,9 Gefitinib 250 mg/día 84,6 8,4 30,6 Gemcitabina mg/m 2 días 1 y 8 + cisplatino 80 mg/m 2 día 1, ciclos de 21 días x 9 ciclos 37,5 6,7 26,5 Gefitinib 250 mg/día 73,7 10,8 30,5 Paclitaxel 200 mg/m 2 + carboplatino (AUC=6), ambos día 1, ciclos de 21 días, más de 3 ciclos 30,7 5,4 23,6 Gefitinib 250 mg/día 62,1 9,2 30,9 Mitsudomi T, et al. Docetaxel 60 mg/m 2 + cisplatino 80 mg/m 2, ambos día 1, ciclos de 21 días, de 3 a 6 ciclos OPTIMAL Zhou C, et al EURTAC Rossel R, et al. 32,2 6,3 ND Erlotinib 150 mg/día 83,0 13,1 ND Gemcitabina mg/m 2 días 1 y 8 + carboplatino (AUC = 5) día 1, ciclos de 21 días, x 4 ciclos 36,0 4,6 ND Erlotinib 150 mg/día 55,0 9,4 18,9 Doblete con quimioterapia estándar basada en platino* * Opciones de doblete con quimioterapia estándar basada en platino: - gemcitabina mg/m 2 días 1 y 8 + cisplatino 75 mg/m 2, día 1 - docetaxel 75 mg/m 2 día 1 + cisplatino 75 mg/m 2, día 1 - docetaxel 75 mg/m 2 día 1 + carboplatino (AUC = 6) día 1 - gemcitabina mg/m 2 días 1 y 8 + carboplatino (AUC = 5) día 1 AUC = área bajo la curva ND = datos no disponibles RC = respuesta completa RP = respuesta parcial SLP = supervivencia libre de progresión SG = supervivencia global 11,0 5,2 14,4 En las Tablas 4 y 5 se indican las principales características de los ECAs de gefitinib y erlotinib frente a quimioterapia, en pacientes previamente no tratados con CPNM avanzado o metastásico, con mutación activadora EGFR. En la Tabla 6 se indican los resultados de eficacia de cada uno de los estudios incluidos en la RS. < 26 >
What Went Wrong? Failure of MetMab with Tarceva in Advanced 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:
Erlotinib (Tarceva) package insert (locally hosted backup). Original source: www.gene.com/gene/products/information/p...ceva-prescribing.pdf, accessed 5/14/2013.
Stop taking erlotinib and call your doctor at once if you have a serious side effect such as:
The PBAC noted that the key EURTAC trial in mutation positive patients suggested a statistically significant and potentially clinically important benefit for erlotinib monotherapy over platinum-based chemotherapy in terms of an additional median progression-free survival of approximately 4.5 months (log rank p < 0.0001, 26 January 2011 cut-off) compared to platinum chemotherapy. Because the EURTAC trial allowed for switching (cross-over) on disease progression, the results for overall survival inform a comparison of early versus late erlotinib; and they currently show no benefit (as at 26 January 2011 cut-off, log rank p = 0.8702). The PBAC noted that the comparison of early versus late erlotinib is relevant in the Australian context because erlotinib is currently listed second-line in unselected patients. Thus the clinical benefit for EGFR activating mutation positive patients of listing erlotinib as first-line treatment in addition to second-line treatment is an improvement in quality of life, but not a prolongation of life.
microgorod24.ru/forum/ochered-1/656-post...17-erlotinib-tribute
No clinically relevant interaction of bevacizumab was observed on the pharmacokinetics of co-administered interferon alpha 2a, erlotinib (and its active metabolite OSI-420), or the chemotherapies irinotecan (and its active metabolite SN38), capecitabine, oxaliplatin (as determined by measurement of free and total platinum), and cisplatin. Conclusions on the impact of bevacizumab on gemcitabine pharmacokinetics cannot be drawn.
Patient characteristics. After a review of EGFR genotyped patients in our centers from 2004 to 2008, we identified 18 EGFR mutated patients that had received gefitinib and erlotinib. Clinical, demographic, pathologic, and molecular characteristics of this cohort are displayed in Table 1. Sixty-one percent of patients were women (11 of 18) and the majority never smokers (11 of 18). Ages varied between 43 and 80 years (Table 1 ). Almost all (16 of 18) patients had adenocarcinoma as the main histologic type of their tumor. These characteristics are similar to historic cohorts of EGFR mutated tumors (17 ). Exon 19 deletion-containing tumors were found in 13 (72%) patients, L858R mutations in 4 (22%) patients, and L861Q in 1 patient (Table 1 ).
"ASPIRATION supports the efficacy of first-line erlotinib therapy in patients with EGFR mutation-positive NSCLC and that treatment beyond progression is feasible and may delay salvage therapy in selected patients," the authors write.
Treatment with TKI and chemotherapy was well tolerated. TKI-patients had a significantly longer OS from progression on TKI (case–control: median 14.5 vs. 2.0 months, HR 0.154) and longer OS from diagnosis of lung cancer (case–control: median 54.5 vs. 28.3 months, HR 0.474). An activating EGFR mutation was detected in 13 of the 23 patient tested (57%). Both among patients with and without detection of an activating EGFR mutation, those treated with erlotinib beyond progression had a longer survival.
Pancreatic Cancer Bevacizumab Avastin™ Anti-VEGF monoclonal antibody rhuMAb-VEGF Erlotinib
“We used a matched-pair design to maximize the reduction of potential bias due to the retrospective nature of study, although the results regarding differences in side effects between the two drugs were not fully determined in this study,” said lead author Myung-Ju Ahn, MD . of Samsung Medical Center, Sungkyunkwan University School of Medicine. Seoul, South Korea. “Based on these results, both gefitinib and erlotinib can be recommended for the treatment of patients with EGFR -mutant NSCLC.”
tsariki.ru/forum/vakansii-v-rajone-tsari...6-16-46-erlonat-wiki
Drug: Vinorelbine (Navelbine) Drug: Erlotinib
Erlotinib in Treating Patients With Solid Tumors and Liver or Kidney Dysfunction
stom05.ru/kunena/reklamnyj-razdel/3003-p...harmacokinetics.html
This labeling supplement is based on the results of the IUNO trial, a randomized, double-blind, placebo-controlled study of erlotinib administered as maintenance therapy in 643 patients with advanced NSCLC who had not experienced disease progression or unacceptable toxicity during four cycles of platinum-based first-line chemotherapy. Patients whose tumors harbored activating EGFR mutations (exon 19 deletions or exon 21 L858R mutations) were excluded from the study. Participants were randomly assigned to receive erlotinib (n = 322) or placebo (n = 321) orally once daily until disease progression or unacceptable toxicity occurred. After progression on initial therapy, the patients were eligible to enter an open-label phase. Fifty percent of patients treated with erlotinib entered the open-label phase and received chemotherapy, while 77% of patients given placebo entered the open-label phase and received erlotinib.
Establishment of an erlotinib-resistant cell line
23 Rudin CM. Liu W. Desai A. et al. Pharmacogenomic and pharmacokinetic determinants of erlotinib toxicity. J Clin Oncol. 2008 ; 26. 1119 - 1127.
Erlotinib metabolism and drug adjustments
Sales of the best Erlotinib hydrochloride /OSI-774/cas: 183319-69-9
Erlotinib is in Pregnancy Category D. Both breast-feeding and pregnancy should be avoided in patients receiving erlotinib. 4
Motesanib + Gemcitabine + Erlotinib
www.clubmycity.ru/forum/2-dobro-pozhalov...nd-coughing-up-blood
Neither erlotinib (small decrease) nor bevacizumab (small increase) administered alone had a significant impact on tumour cell proliferation ( P >0.05 vs controls) ( Figure 3 ). In contrast, RT application induced cell proliferation ( P = 0.007 vs controls). This RT-related effect on tumour cell proliferation was diminished by the presence of erlotinib + bevacizumab to a level similar to the controls ( P = 0.0037 vs RT; P = 0.587 vs controls).
Erlotinib was kindly provided by Roche (Neuilly sur Seine, France) and bevacizumab by our institution's pharmacy. Working solutions were prepared as follows: erlotinib (7.5   g   l −1 ) was suspended in 0.9 % NaCl and 0.01 % Tween 80, and bevacizumab (750   mg   l −1 ) was diluted in 0.9 % NaCl. For both drugs, the concentrations were adjusted so as to include the daily dose in 0.2   ml of drug suspension. Dulbecco's modified Eagle's medium (DMEM), penicillin, streptomycin and glutamine were purchased from Whittaker (Verviers, Belgium). Fetal bovine serum (FBS) was obtained from Dutscher (Brumath, France).
Patients were treated preoperatively with erlotinib (150 mg once daily for 3 weeks) up to 48 hours before surgery. Plasma samples were collected during treatment. Surgical resection involved radical resection of the lung tumor and tumor biopsies were frozen directly after surgery. Erlotinib and O-desmethyl erlotinib concentrations in lung tumor tissue and predose plasma were determined using high performance liquid chromatography coupled with tandem mass spectrometry.
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A 66-year-old African-American man presented to the emergency department with dyspnea and dry cough. He had an oxygen saturation of 83% on room air. Four months before presentation, the patient was diagnosed with metastatic non-small cell lung cancer (NSCLC). The patient was started on 150 mg of erlotinib daily, five days before presentation after failure of carboplatin and paclitaxel chemotherapy three months earlier. Two days before presentation, a dry cough and a low-grade fever were reported by the patient. He experienced worsening of the cough and dyspnea. The patient was an ex-smoker. Physical examination revealed a temperature of 37.7°C, a blood pressure of 127/65 mmHg, a respiratory rate of 24 breaths/min and a heart rate of 88 beats/min. Chest auscultation was significant for bilateral diffuse crackles, and jugular venous distention was not present. A chest radiograph showed bilateral alveolar-patterned lung opacifications ( Figure 1A ). An echocardiogram showed normal left ventricular systolic and diastolic functions and a computed tomography (CT) scan of the chest showed bilateral ground-glass infiltrates ( Figure 2A ). Pulmonary embolism was not seen on a CT angiogram of the chest. The patient developed respiratory failure and subsequently intubation and mechanical ventilation became necessary. Bronchoscopy showed no evidence of diffuse alveolar hemorrhage (DAH). Bronchoalveolar lavage (BAL) cultures were negative for bacterial, viral, Legionella . Mycobacterium and fungal pathogens. BAL total cell count was 117×10 5 cells/mL and BAL differential cell count showed 76% neutrophils. Erlotinib-associated acute pneumonitis was diagnosed and 250 mg of methylprednisolone intravenously, every 6 h for three days, was started. Corticosteroid therapy was continued with 60 mg of prednisone daily thereafter. Hypoxemia improved after four days and the patient was extubated. A repeat chest radiograph showed marked reduction of the bilateral lung opacities. Two weeks after presentation, the patient was transferred to a rehabilitation centre on tapering prednisone. He still required supplemental oxygen at rest.
Tarceva (erlotinib) is the first next-generation treatment for non-small cell lung cancer (NSCLC) to win marketing approval and has shown it can help prolong the lives of patients with advanced lung cancer, compared to existing treatments.
Generic Erlotinib Dosage and Administrartion
This appears to be the first adequately powered evaluation of erlotinib/bevacizumab specifically in patients with EGFR mutations.