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For patients with activating mutations to the EGFR receptor kinase, small molecule specific inhibitors Iressa (gefintinib) or Tarceva (erlotinib) are administered as front-line treatments. But, non-small cell lung cancers develop resistance after about one year of treatment via a single recurrent missense mutation (T790M) to the tyrosine kinase. This is similar to resistance observed in patients with CML (Chronic Myeloid Leukemia) following treatment Gleevec (imatinib), which is mediated by a mutation to the Bcr-Abl transgene. Continue reading →
In Study NP16787, subjects were planned to receive 100 mg erlotinib orally once a day for 8 days. Twenty-two subjects participated in this study but only 11 subjects received the planned 8 days of treatment because of premature termination of the study following a serious adverse event (dyspnea) and a Grade 4 laboratory abnormality (Grade 4 elevation in creatine phosphokinase). In the subject with elevated creatine phosphokinase, thyroid function tests and anti-muscle autoantibodies were negative. The subject denied any injury and he did not receive any injections. He also confirmed that he had not performed any physical activity. This event did not qualify as a serious adverse event. Skin reactions were experienced by most subjects (19/22, 86%) of whom 17 experienced mild rash, reaching Grade 2 in only 1 subject. Gastrointestinal events were also frequent, but only 1 subject required loperamide for treatment of diarrhea.
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The serum concentration of Erlotinib can be increased when it is combined with Conivaptan.
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This trial is designed to investigate the safety, tolerability and the effectiveness when OSI-774 (tarceva) is combined with oxaliplatin and capecitabine in treating patients with metastatic colorectal cancer.
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My wife has been using Tarceva for 2 weeks now. Her rash started within 5 days of starting this medication. For her face she is using a mixture of milk & turmeric powder. She takes a tablespoon of milk & 2 pinches of turmeric and mixes them to a creamy paste. With a cotton ball she dabs it over her entire face. It has had a very cooling effect & helps a lot with the rash. She does this twice daily… in the early morning before showering & at night before bed. Just be aware that turmeric stains are extremely difficult to remove from porcelain sinks and also from linens. Hope this helps.
Tarceva ha indotto benefici sintomatici prolungando significativamente, rispetto al placebo, il tempo al peggioramento della tosse, della dispnea e del dolore.
As described in a prior post, chemotherapy after surgery is often recommended after surgery, at least for a subset of patients with stage IB to IIIA (without mediastinal lymph node involvement) NSCLC. based on a potential to increase cure long-term survival compared to surgery alone. At this point, two forms of targeted therapy (erlotinib, or Tarceva, as a single agent in second- and third-line advanced NSCLC. and bevacizumab, or Avastin, combined with carboplatin and paclitaxel for first-line treatment of advanced NSCLC ) have been approved by the FDA for advanced NSCLC because they have demonstrated an improvement in survival. At this point, however, we don’t know whether adding targeted therapies as a strategy in earlier stage NSCLC can increase cure rates. But one key trial that is evaluating this possibility is the RADIANT trial.
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Drs. Nasser Hanna and Melissa Johnson discuss new trial evidence for the use of adjuvant Erlotinib for early-stage lung cancer.
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MedKoo Cat#: 100300 Name: Erlotinib hydrochloride CAS#: 183319-69-9 (Erlotinib hydrochloride); 183321-74-6 (Erlotinib free base). Chemical Formula: C22H24ClN3O4 Exact Mass: Molecular Weight: 429.9 Elemental Analysis: C, 61.47; H, 5.63; Cl, 8.25; N, 9.77; O, 14.89
14 Katayama T. Shimizu J. Suda K et al . Efficacy of erlotinib for brain and leptomeningeal metastases in patients with lung adenocarcinoma who showed initial good response to gefitinib. J Thorac Oncol 2009 ; 4. 1415 – 9.
. Final evaluation of Tarceva (erlotinib) in combination with FOLFOX4 in patients with solid tumors. Clin Cancer Res 2003 ; 9. 6095s. (Abstr A108).
All treatment was delivered in an outpatient setting. Erlotinib was administered at a continuous, daily dose of 150   mg. Patients were instructed to take erlotinib with at least 200   ml of water each morning before breakfast, and they had to fast for at least 2   h before and 1   h after treatment. A cycle was considered to be 28 days. Before starting study medication and on day 8 of therapy, patients underwent tumour biopsies, unless medically contraindicated. Tumour biopsies were performed as either ultrasound-guided liver core needle biopsies or tissue biopsies performed during a colonoscopic procedure if possible.
Core needle tumour biopsies were taken before and after 1 week of treatment with erlotinib. They were collected into 10 % neutral-buffered formalin, fixed overnight before transferred to 70 % ethanol and shipped to Princess Margaret Hospital for processing into paraffin blocks. Sections of 4   μ m thickness was cut onto Surgipath x-tra slides with pretreatment and on-treatment specimen placed side by side on the same slide. Sections were dewaxed in xylene and rehydrated through graded alcohol. Epidermal growth factor receptor status was determined on sections cut from archival paraffin blocks after pretreatment in 0.4 % pepsin, pH 2.0, and stained for immunohistochemistry with EGFR monoclonal antibody (Zymed, Markham, Ontario, Canada; clone 31G7, 1  .   50 dilution). Antigen retrieval was performed on the other slides in a Milestone T / T Mega microwave oven for 10   min at 120°C in 10   m M citrate buffer, pH 6.0. After cooling, sections were covered with normal serum and then incubated in primary antibodies. Tumour biopsies were stained using immunofluorescence techniques and dual labelling for cytokeratin (cocktail of Dako monoclonal antibodies to AE1 / AE3, HMWK, CK7, CK20 or Dako rabbit polyclonal antikeratin wide spectrum screening) was usually carried out to help with the identification of epithelial tumour cells. Slides were rinsed in phosphate-buffered saline (PBS) and the appropriate secondary antibodies (Cy3 conjugated for the pharmacodynamic markers and Cy5 conjugated for cytokeratin) were applied for 30   min at room temperature in darkness. After rinsing in PBS, sections were counterstained with the DNA-specific dye 4,6-diamidino-2-phenylindole (DAPI; Roche, Indianapolis, IN, USA) at 1   μ g   ml −1 for 5   min at 4°C, then rinsed twice for 5   min with distilled water and allowed to air dry. Slides were stored in the refrigerator until image analysis was performed.
Mapping of the CI-1033 resistance mutants on to the EGFR-13-JAB structure highlighted three interesting resistance clusters. The first cluster (C797S/G, G796R/C and P794L) was located near the solubilizing and reactive groups of CI-1033 (Figure 3 d). Cys 797 was the most frequently mutated residue identified in our CI-1033 screens (see Supplementary Figure S1c). Cys 797 is critical for irreversible inhibitor binding [21 ], since it contains the thiol group that reacts with CI-1033 to form the covalent bond. Gly 796 is positioned adjacent to the critical Cys 797. whereas Pro 794 is located close to the morpholine group of CI-1033. The second mutation cluster (T790M and M766V/T) is located close to the aniline group of CI-1033 (Figure 3 d). Interestingly, the T790M mutation was significantly less prevalent in the CI-1033 screen when compared with the erlotinib screen (Supplementary Figure S1c). The final cluster observed (V742A, A743S and I744F) was located above the quinazoline ring of CI-1033 (Figure 3 d).
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To evaluate the effect of erlotinib on the PSA response rate in patients with non-metastatic prostate cancer and a rising PSA on androgen deprivation therapy
Hepatic failure and hepatorenal syndrome, including fatal cases, can occur with Tarceva treatment in patients with normal hepatic function; the risk of hepatic toxicity is increased in patients with baseline hepatic impairment.
I managed 28 months of Tarceva incredibly well with acupuncture and am continuing to see how she can help with the hot flashes and night sweats. I’ve been told I respond very well to it and after a session yesterday to help with sleep I did have a better night’s rest than I’ve had in ages. But acupuncture can only help so far. This Clovis is strong!
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Generic Name: erlotinib (Pronunciation: er LOE ti nib)
Before you take TARCEVA