However, this occurred in the N Height Idarubicin Idamycin limit in the Nacktm Mice tolerated. Lower doses were well tolerated Possible and effectively suppresses tumor growth in U87MG. Patients with GBM-F Ll PTEN in general have a poor prognosis negative. In clinical settings are gliomas resistant to EGFR inhibitors, radiation therapy, and most of the alkylating agent. In GBM, k PKI-587 can be effective either as monotherapy or in combination with cytostatic or cytotoxic drugs. Reason enough, these combinations of data showing that the PI3K/mTOR inhibitor in combination with temozolomide Novartis BEZ235 regression of tumor xenografts U87MG caused most derived. A central question for inhibitors of PI3K/mTOR signaling was: K, they can cause tumor regression in clinical pr models OSI-420 EGFR inhibitor Some compounds have responded positively to this question. But here we show how the m Chtige PKI Profile of 587 causes a regression to lower doses and / or fewer hours Frequently than those reported for other inhibitors of the PI3K signaling pathway.
One example is the comparison of PCI with 587 PKI 402, an inhibitor of PI3K/mTOR we have already reported. Aggressive in U87MG glioma tumor model, as a test of the critical Syk inhibition activity T used, PKI 402 to 100 mg / kg U87MG xenograft tumor growth only alleviated. PKI 587 only 25 mg / kg resulted in tumor regression U87MG. Less efficiency in the ICP 402 U87MG model with a shorter half-life of 3.5 hours in plasma that correlates of 14.4 hours for ICP 587th convincing efficacy profile of PKI-587 is more firmly established by direct experimental comparison of PCI with 587 other inhibitors of the PI3K/mTOR signaling. Closing Lich, in contrast to PI3K inhibitors cytotoxic agents that lead to tumor cell G0/G1 arrest, powerful PKI 587 inhibit class 1 PI3Ks can completely the activation of Akt Inhibit complete and may result in induction of apoptosis. This is the desired outcome for cancer cells. PKI 587 antitumor activity and favorable safety profile of drugs in toxicological studies erm It glicht him, phase 1 clinical evaluation in December 2009. The chemotherapy was docetaxel 100 mg/m2 on day 1 every 3 weeks with trastuzumab 8 mg / kg axitinib loading and maintenance dose of 6 mg / kg on day 1 every 3 weeks or vinorelbine 35 mg iv in combination / m2 on day 1 and 8 every three weeks with concurrent trastuzumab as described above. Tumor response was assessed every third cycle by clinical examination, R Ntgen, computed tomography or magnetic resonance imaging with the WHO criteria.
DNA of both HER2 and HER2 ECD assay was, 28 patients completed the study and treatment of a plasma sample was obtained before. One patient died before the second blood sample was taken. Four patients, it was not m Possible to obtain a second blood sample, and one patient a sufficient saturation plasma of the second blood sample for testing HER2 ECD. Thus, a plasma sample for HER2 ECD and HER2 DNA test after the first treatment with trastuzumab and 22 of 23 patients were obtained. DNA was extracted from plasma samples from 20 individuals without cancer, the Department of Clinical Biochemistry, h Consulted Pital University t Aarhus, and the DNA was isolated as a reference material used for the determination of HER-2 DNA. In Similar way was used plasma from 47 patients with diseases other than cancer as a reference material for the determination of HER2 ECD.