New drug-PD-0332991-stops growth brain tumors in animal testing Glioblastoom. Once again with this medication was stopped the tumors grow went. Phase I study in 33 patients with kidney cancer and lymfklier cancer confirms safety of this medium and gives encouraging results. Article update 19 July 2011
19 July 2011: last year came the news that a particular means the growth of outward brain tumors would stop. Meanwhile in New York a phase I study in patients with kidney cancer and done with this medium-lymfklier cancer. In the Academic Hospital of Groningen are now laboratory tests with this medium-done. Here is the abstract of the study with patients from New York:
Phase I study of cyclin-dependent PD 0332991, a kinase inhibitor, administered in 3-week cycles (Schedule 2/1).
Source
Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Abstract
Background: This phase I, open-label, first-in-human study determined dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) or PD 0332991cyclin-dependent kinase, an oral inhibitor with potent anti-proliferative 4/6 activity in vitro/vivo.
Methods: A total of 33 patients with advanced solid tumours retinoblastoma protein-positive lymphoma refractory to standard therapy or non-Disease or for which no therapy was available received once daily (QD) PD 0332991 for 14 days followed by 7 days off treatment (21-day cycles; Schedule 2/1).
Results: Six patients had DLTs (18%; four receiving 200 mg QD; two receiving 225 mg QD); the MTD was 200 mg QD. Treatment-related adverse events occurred in 29, non-haematological patients (88%) during cycle 1 and 27 patients (82%) thereafter. Adverse events were generally mild-moderate. Evaluable patients, one with testicular cancer or 31 achieved a partial response; nine had stable disease (10 cycles in three cases). PD 0332991 was slowly absorbed (mean T (max) 4.2 h) and eliminated (mean half-life 26.7 h). Volume of distribution was large (mean 3241 l) with dose-proportional exposure. Using a maximum effective concentration model, was proportional to exposure neutropenia.
Conclusion: was generally well tolerated0332991 PD , with related mainly to DLTs myelosuppression. The MTD, 200 mg QD, is recommended for phase II study.
- PMID:
- 21610706
- [PubMed-in process]
april 18, 2010: source: Cancer Res. 2010 Apr 15; 70 (8): 3788-38. Epub 2010 Mar 30.
Scientists at the University of San Fransisco in pre-clinical studies report that they in the laboratory as well as in animals a medication PD-0332991 have tested that the growth of tumors in the brain (glioblastomen) would stop. Several studies showed that mice so long they took this medication with a brain tumor, and the tumor itself doorleefden not grew. Once the scientists stopped with this medication, the tumors grow again and the mice died. The mice in the control group were already long dead gone to the tumors.
The medicine saves only to those tumors that a particular gene P16 miss in conjunction with certain molecules, the cyclin-dependent kinasen 4 and 6 (CDK4/6) this gene is present, or where little. The status of this gene in combination with CDK4/6, is easy to establish in advance to the treatment, the researchers said. The scientists also say that they investigate and try this medication now in animals injected with tumors of Kahler-multiple myeloma and breast cancer.
Here's a post about this medication of clinical trials:
Cancer Res. 2010 Apr 15; 70 (8): 3788-38. Epub 2010 Mar 30.
Cyclin-dependent kinases Pharmacologic inhibition or 4 and 6 arrests the growth of glioblastoma multiforme GA xenografts.
Solomon DA Michaud K, E Oermann,, Kim JS, Zhong WZ, Prados MD, Ozawa T, James CD, Waldman T.
Department of Neurological Surgery, Helen Diller Comprehensive Cancer Center, University of California San Francisco, California 94143-0520, USA.
Abstract
Activation of cyclin-dependent kinases 4 and 6 (cdk4/6) occurs in the majority of tumors, and glioblastoma multiforme (GBM) represents a promising molecular target for the development of small molecule inhibitors. In the current study, we investigated the molecular determinants and cell lines and in vivo response or various GBM xenografts to PD-cdk4/6-0332991, a specific inhibitor. In vitro testing of PD-0332991 against a panel or GBM cell lines revealed a potent G (1) cell cycle arrest and induction of senescence in each retinoblastoma protein (Rb) or 16-proficient cell lines regardless of other genetic lesions, whereas 5 cell lines with resistant to inactivation or Rb were completely homozygous treatment. Short hairpin RNA expression conferred resistance or depletion or Rb GBM cells to PD-0332991, further demonstrating a requirement or Rb for sensitivity to cdk4/6 inhibition. PD-0332991 was found to efficiently cross the blood-brain barrier and proved highly effective in suppressing the growth of tumors, including those that had GA GBM xenograft recurred after initial therapy with temozolomide. Remarkably, no mice receiving PD-0332991 died as a result of disease progression while on therapy. Additionally, the combination of PD-0332991 and radiation therapy resulted in significantly increased survival benefit compared with either therapy alone. In total, our results support clinical trial evaluation of PD-0332991 against newly diagnosed as well as recurrent GBM, and indicate that Rb status is the primary determinant of potential benefit from this therapy. (c) 2010 AACR.
PMID: 20354191 [PubMed-in process]
