Reversible pan-HER kinase inhibitors Sample Clauses

Reversible pan-HER kinase inhibitors. X. Xxxxxxxxx Lapatinib (Tykerb), the first dual inhibitor of the EGFR and HER2 tyrosine kinases, binds to the receptor ATP binding pocket, thereby preventing receptor phosphorylation and subsequent activation of downstream pathways. A trial of single-agent lapatinib in trastuzumab-refractory advanced breast cancer showed a 12.8% response rate with a median time to progression in the single-agent trial of approximately 4 months (Xxxxxxxxx et al, 2009). As with trastuzumab treatment, patients who initially responded to lapatinib eventually developed resistance, making it necessary to elucidate mechanisms by which resistance develops. A Phase III trial comparing lapatinib plus capecitabine with capecitabine alone indicated the combination treatment was associated with improved overall response rate versus single agent capecitabine (22% vs 14%) and significantly increased median TTP (8.4 vs 4.4 months) in patients with pre-treated HER2-over-expressing advanced disease (Xxxxx et al, 2006). Lapatinib was subsequently approved by the FDA in 2007 for use in combination with capecitabine for treatment in patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have previously been treated with an anthracycline, taxane, and trastuzumab (Xxxxxx et al, 2008). Thus, lapatinib is an important and effective therapy for a subset of HER2-over-expressing metastatic breast cancers that have progressed on trastuzumab. However, similar to trastuzumab, the median duration of response to lapatinib was less than one year, and a majority of trastuzumab pre-treated patients (almost 80%) failed to respond to lapatinib. Combination trastuzumab plus lapatinib treatment has been shown to induce apoptosis in part via down-regulation of survivin in cell culture and animal models (Xxx et al, 2005). Initial phase I data suggested the combination is well-tolerated and elicits partial or complete responses in a subset of patients who have progressed on prior trastuzumab therapy (Xxxxxxxxx et al, 2008). The combination has been tested clinically in advanced phase trials in patients who have progressed on trastuzumab-based regimens. Progression-free survival and quality of life were improved in patients treated with the combination versus lapatinib alone (Xx et al, 2011). EGF104900 showed the combination was superior to lapatinib alone in the trastuzumab-resistant setting, with a clinical benefit rate of 24.7% versus 12.4% (Xxxxxxxxx et al, 2010). A potentially ...
AutoNDA by SimpleDocs

Related to Reversible pan-HER kinase inhibitors

  • Hepatitis B Vaccine Where the Hospital identifies high risk areas where employees are exposed to Hepatitis B, the Hospital will provide, at no cost to the employees, a Hepatitis B vaccine.

  • Human Leukocyte Antigen Testing This plan covers human leukocyte antigen testing for A, B, and DR antigens once per member per lifetime to establish a member’s bone marrow transplantation donor suitability in accordance with R.I. General Law §27-20-36. The testing must be performed in a facility that is: • accredited by the American Association of Blood Banks or its successors; and • licensed under the Clinical Laboratory Improvement Act as it may be amended from time to time. At the time of testing, the person being tested must complete and sign an informed consent form that also authorizes the results of the test to be used for participation in the National Marrow Donor program.

  • Rhytidectomy Scar revision, regardless of symptoms. • Sclerotherapy for spider veins. • Skin tag removal. • Subcutaneous injection of filling material. • Suction assisted Lipectomy. • Tattooing or tattoo removal except tattooing of the nipple/areola related to a mastectomy. • Treatment of vitiligo. • Standby services of an assistant surgeon or anesthesiologist. • Orthodontic services related to orthognathic surgery. • Cosmetic procedures when performed primarily: o to refine or reshape body structures or dental structures that are not functionally impaired; o to improve appearance or self-esteem; or o for other psychological, psychiatric or emotional reasons. • Drugs, biological products, hospital charges, pathology, radiology fees and charges for surgeons, assistant surgeons, attending physicians and any other incidental services, which are related to cosmetic surgery.

  • Biological Samples If so specified in the Protocol, Institution and Principal Investigator may collect and provide to Sponsor or its designee Biological Samples (“Biological Samples”). 12.2.

  • Influenza Vaccine Upon recommendation of the Medical Officer of Health, all employees shall be required, on an annual basis to be vaccinated and or to take antiviral medication for influenza. If the costs of such medication are not covered by some other sources, the Employer will pay the cost for such medication. If the employee fails to take the required medication, she may be placed on an unpaid leave of absence during any influenza outbreak in the home until such time as the employee has been cleared by the public health or the Employer to return to the work environment. The only exception to this would be employees for whom taking the medication will result in the employee being physically ill to the extent that she cannot attend work. Upon written direction from the employee’s physician of such medical condition in consultation with the Employer’s physician, (if requested), the employee will be permitted to access their sick bank, if any, during any outbreak period. If there is a dispute between the physicians, the employee will be placed on unpaid leave. If the employee gets sick as a reaction to the drug and applies for WSIB the Employer will not oppose the application. If an employee is pregnant and her physician believes the pregnancy could be in jeopardy as a result of the influenza inoculation and/or the antiviral medication she shall be eligible for sick leave in circumstances where she is not allowed to attend at work as a result of an outbreak. This clause shall be interpreted in a manner consistent with the Ontario Human Rights Code.

  • Library CONTRACTOR shall provide an inmate law library in compliance with Rule 33-501.301, F.A.C., FDC’s Policy 501.301, and ACA Standards.

  • PROGENY Unmodified descendant from the MATERIAL, such as virus from virus, cell from cell, or organism from organism.

  • Geological and Archeological Specimens If, during the execution of the Work, the Contractor, any Subcontractor, or any servant, employee, or agent of either should uncover any valuable material or materials, such as, but not limited to, treasure trove, geological specimens, archival material, archeological specimens, or ore, the Contractor acknowledges that title to the foregoing is vested in the Owner. The Contractor shall notify the Owner upon the discovery of any of the foregoing, shall take reasonable steps to safeguard it, and seek further instruction from the Design Professional. Any additional cost incurred by the Contractor shall be addressed under the provision for changed conditions. The Contractor agrees that the Geological and Water Resources Division and the Historic Preservation Division of the Georgia Department of Natural Resources may inspect the Work at reasonable times.

  • Preceptor A per diem Registered Nurse 2 may serve as a preceptor after successfully completing a preceptor workshop or equivalent documented training and agreeing to and being appointed to be specifically responsible for planning, organizing, and evaluating the new skill development of one or more RNs as appropriate enrolled in a defined orientation program, the parameters of which have been set forth in writing by the Employer. This includes teaching, clinical supervision, role modeling, feedback, evaluation (verbal and written) and follow up of the new or transferring employee. The per diem RN 2 preceptor is eligible to receive preceptor premium pay when actually engaged in preceptor role responsibilities with/on behalf of the orienting RN. A per diem RN 2 substituting for the original preceptor during a period of absence and who has been designated to carry out the preceptor's complete responsibility (including following and/or adjusting the plan to meet learning needs and providing oral and written evaluation input) will receive preceptor pay. A preceptor may be assigned to a student when it is determined by the Employer that the employee has completed the required preceptor training or has agreed to and been appointed a preceptor. The employee is specifically responsible for planning, organizing, and evaluating the new skill development of the student as appropriately enrolled in a defined program, the parameters of which have been set forth in writing by the Employer. This includes teaching, clinical supervision, role modeling, feedback, evaluation (verbal and written) and follow up of the student.

  • Geographical Indications 1. Each Party shall recognise that geographical indications may be protected through a trade xxxx or sui generis system or other legal means in accordance with its laws and regulations.

Time is Money Join Law Insider Premium to draft better contracts faster.