Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs
dc.contributor.author | Conrad, Charles | en_US |
dc.contributor.author | Schiff, David | en_US |
dc.contributor.author | Chang, Susan M. | en_US |
dc.contributor.author | Kuhn, John E. | en_US |
dc.contributor.author | Wen, Patrick | en_US |
dc.contributor.author | Greenberg, Harry S. | en_US |
dc.contributor.author | Fink, Karen | en_US |
dc.contributor.author | Robins, H. Ian | en_US |
dc.contributor.author | Cloughesy, Timothy | en_US |
dc.contributor.author | De Angelis, Lisa | en_US |
dc.contributor.author | Razier, Jeffrey | en_US |
dc.contributor.author | Hess, Kenneth | en_US |
dc.contributor.author | Dancey, Janet | en_US |
dc.contributor.author | Prados, Michael D. | en_US |
dc.date.accessioned | 2006-09-11T15:50:53Z | |
dc.date.available | 2006-09-11T15:50:53Z | |
dc.date.issued | 2004-11 | en_US |
dc.identifier.citation | Chang, Susan M.; Kuhn, John; Wen, Patrick; Greenberg, Harry; Schiff, David; Conrad, Charles; Fink, Karen; Robins, H. Ian; Cloughesy, Timothy; De Angelis, Lisa; Razier, Jeffrey; Hess, Kenneth; Dancey, Janet; Prados, Michael D.; (2004). "Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs." Investigational New Drugs 22(4): 427-435. <http://hdl.handle.net/2027.42/45250> | en_US |
dc.identifier.issn | 0167-6997 | en_US |
dc.identifier.issn | 1573-0646 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/45250 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=15292713&dopt=citation | en_US |
dc.description.abstract | Objectives : CCI-779 is an ester of the immunosuppressive agent sirolimus (rapamycin) that causes cell-cycle arrest at G1 via inhibition of key signaling pathways resulting in inhibition of RNA translation. Antitumor activity has been demonstrated using cell lines and animal models of malignant glioma. Patients receiving enzyme-inducing anti-epileptic drugs (EIAEDs) can have altered metabolism of drugs like CCI-779 that are metabolized through the hepatic cytochrome P450 enzyme system. The objectives of this study were to determine the pharmacokinetic profile and the maximum tolerated dose of CCI-779 in patients with recurrent malignant gliioma taking EIAEDs. Study design: The starting dose of CCI-779 was 250 mg intravenously (IV) administered weekly on a continuous basis. Standard dose escalation was performed until the maximum tolerated dose was established. Toxicity was assessed using the National Cancer Institute common toxicity criteria. Results : Two of 6 patients treated at the second dose level of 330 mg sustained a dose-limiting toxicity: grade III stomatitis, grade 3 hypercholesterolemia, or grade 4 hypertriglyceridemia. The maximum tolerated dose was reached at 250 mg IV. Pharmacokinetic profiles were similar to those previously described, but the area under the whole blood concentration-time curve of rapamycin was 1.6 fold lower for patients on EIAEDs. Conclusions : The recommended phase II dose of CCI 779 for patients on enzyme-inducing antiepileptic drugs is 250 mg IV weekly. A phase II study is ongoing to determine the efficacy of this agent. | en_US |
dc.format.extent | 117658 bytes | |
dc.format.extent | 3115 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Kluwer Academic Publishers; Springer Science+Business Media | en_US |
dc.subject.other | Medicine & Public Health | en_US |
dc.subject.other | Pharmacology/Toxicology | en_US |
dc.subject.other | Oncology | en_US |
dc.subject.other | Chemotherapy | en_US |
dc.subject.other | Rapamycin | en_US |
dc.subject.other | CCI-779 | en_US |
dc.subject.other | Toxicity | en_US |
dc.title | Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Chemistry | en_US |
dc.subject.hlbsecondlevel | Radiology | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbsecondlevel | Chemical Engineering | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Engineering | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan, USA | en_US |
dc.contributor.affiliationother | University of Virginia, USA | en_US |
dc.contributor.affiliationother | University of California, San Francisco | en_US |
dc.contributor.affiliationother | University of Texas, San Antonio | en_US |
dc.contributor.affiliationother | Dana Farber Cancer Institute, USA | en_US |
dc.contributor.affiliationother | MD Anderson Cancer Center, USA | en_US |
dc.contributor.affiliationother | University of Texas, Southwestern | en_US |
dc.contributor.affiliationother | Unversity of Wisconsin, USA | en_US |
dc.contributor.affiliationother | University of California, Los Angeles | en_US |
dc.contributor.affiliationother | Memorial Sloan Kettering Cancer Center, USA | en_US |
dc.contributor.affiliationother | Memorial Sloan Kettering Cancer Center, USA | en_US |
dc.contributor.affiliationother | MD Anderson Cancer Center, USA | en_US |
dc.contributor.affiliationother | Cancer Therapy Evaluation Program, National Cancer Institute, USA | en_US |
dc.contributor.affiliationother | University of California, San Francisco | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 15292713 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/45250/1/10637_2004_Article_5273867.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1023/B:DRUG.0000036685.72140.03 | en_US |
dc.identifier.source | Investigational New Drugs | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.