Safety and Pharmacokinetics of Escalated Doses of Weekly Intravenous Infusion of CCI-779, a Novel mTOR Inhibitor, in Patients With Cancer

Abstract

CCI-779 displayed no immunosuppressive effects with manageable and reversible adverse events at doses up to 220 mg/m(2), the highest dose tested. Based on our results, weekly doses of 25, 75, and 250 mg CCI-779 not based on classical definitions of maximum-tolerated dose are being tested in phase II trials in patients with breast and renal cancer.

References

Page 1

	Year	Citations
Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor Markus Guba, Philipp von Breitenbuch, Markus Steinbauer, Nature Medicine OncologyAngiogenesisMetastatic Tumor GrowthMedicinePathology	2002	1.7K
Continual Reassessment Method: A Practical Design for Phase 1 Clinical Trials in Cancer John O’Quigley, Margaret S. Pepe, Lloyd D. Fisher Biometrics Cancer ManagementClinical EndpointDose Toxicity CurveOncologyClinical Trials	1990	1.6K
Phase I and Pharmacologic Study of OSI-774, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced Solid Malignancies Manuel Hidalgo, Lillian L. Siu, John Nemunaitis, Journal of Clinical Oncology	2001	997
Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR Mehran S. Neshat, Ingo K. Mellinghoff, Chris Tran, Proceedings of the National Academy of Sciences	2001	973
Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells Candace J. Sabers, Mary M. Martin, Gregory J. Brunn, Journal of Biological Chemistry	1995	872
Phase I Safety, Pharmacokinetic, and Pharmacodynamic Trial of ZD1839, a Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Five Selected Solid Tumor Types José Baselga, Danny Rischin, Malcolm Ranson, Journal of Clinical Oncology	2002	829
A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. A Sekulić, Christine C. Hudson, J L Homme, PubMed ImmunologyMtor MutantsTumor BiologyInflammationMammalian Target	2000	716
An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in<i>Pten</i><sup>+/−</sup>mice Katrina Podsypanina, Richard Lee, Chris Politis, Proceedings of the National Academy of Sciences	2001	571
Regulation of eIF-4E BP1 Phosphorylation by mTOR Kenta Hara, Kazuyoshi Yonezawa, Mark T. Kozlowski, Journal of Biological Chemistry	1997	514
mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Ker Yu, Lourdes Toral‐Barza, Carolyn Discafani, Endocrine Related Cancer Breast OncologyCell CycleCancer BiologyTumor BiologySensitive Lines	2001	418

Page 1