The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Safety and Pharmacokinetics of Escalated Doses of Weekly Intravenous Infusion of CCI-779, a Novel mTOR Inhibitor, in Patients With Cancer
Open accessAbstract
Purpose: To establish the safety, tolerability, and pharmacokinetic parameters of CCI-779, a selective inhibitor of the mammalian target of rapamycin, in patients with advanced cancer. Patients and Methods: Using a modified continuous reassessment method, we performed a phase I with pharmacokinetic study of CCI-779 given as a weekly 30 minutes intravenous (IV) infusion. Results: Twenty-four patients received CCI-779 at doses ranging 7.5 to 220 mg/m 2. No immunosuppressive effect was reported. Dose-limiting thrombocytopenia occurred in two patients at 34 or 45 mg/m 2. At 220 mg/m 2, dose-limiting toxicities consisted of manic-depressive syndrome, stomatitis, and asthenia in two of nine patients, preventing further dose escalation. The most frequent drug-related toxicities were acne-like, maculopapular rashes and mucositis or stomatitis. All toxicities were reversible on treatment discontinuation. Maximum concentration and area under the concentration-time curve increase sub-proportionally with dose. Mean steady-state volume of distribution ranged from 127 to 385L. Sirolimus was a major metabolite (metabolite-to-parent ratio range, 2.5 to 3.5). Whole blood clearance was nonlinear, ranging from 19 to 51 L/h (34 to 220 mg/m 2). Variability predicted with flat doses appears comparable with data based on body-surface area–normalized treatment. Partial responses were observed in one patient with renal clear-cell carcinoma and in one patient with breast adenocarcinoma. Conclusion: 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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
TOR, a Central Controller of Cell Growth
Schmelzle, T., & Hall, M. N. (2000) · Cell · doi:10.1016/s0092-8674(00)00117-3 · Cited by 1,924
Guba, M., von Breitenbuch, P., Steinbauer, M., Koehl, G., Flegel, S., Hornung, M., Bruns, C. J., Zuelke, C., Farkas, S., Anthuber, M., et al. (2002) · Nature Medicine · doi:10.1038/nm0202-128 · Cited by 1,739
Continual Reassessment Method: A Practical Design for Phase 1 Clinical Trials in Cancer
O'Quigley, J., Pepe, M., & Fisher, L. (1990) · Biometrics · doi:10.2307/2531628 · Cited by 1,577
Status of Epidermal Growth Factor Receptor Antagonists in the Biology and Treatment of Cancer
Mendelsohn, J., & Baselga, J. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.01.504 · Cited by 1,255
Hidalgo, M., Siu, L. L., Nemunaitis, J., Rizzo, J., Hammond, L. A., Takimoto, C., Eckhardt, S. G., Tolcher, A., Britten, C. D., Denis, L., et al. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.13.3267 · Cited by 1,001
Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR
Neshat, M. S., Mellinghoff, I. K., Tran, C., Stiles, B., Thomas, G., Petersen, R., Frost, P., Gibbons, J. J., Wu, H., & Sawyers, C. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171076798 · Cited by 969
Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells
Sabers, C. J., Martin, M. M., Brunn, G. J., Williams, J. M., Dumont, F. J., Wiederrecht, G., & Abraham, R. T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.2.815 · Cited by 887
Baselga, J., Rischin, D., Ranson, M., Calvert, H., Raymond, E., Kieback, D. G., Kaye, S. B., Gianni, L., Harris, A., Bjork, T., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.03.100 · Cited by 829
Self-citationSekulić, A., Hudson, C. C., Homme, J. L., Yin, P., Otterness, D. M., Karnitz, L. M., & Abraham, R. T. (2000) · PubMed · Cited by 708
The rapamycin-sensitive signal transduction pathway as a target for cancer therapy
Hidalgo, M., & Rowinsky, E. K. (2000) · Oncogene · doi:10.1038/sj.onc.1204091 · Cited by 582
Cited by
Dose Escalation Methods in Phase I Cancer Clinical Trials
Le Tourneau, C., Lee, J. J., & Siu, L. L. (2009) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djp079 · Cited by 867
Chapter 2 PI3K/PTEN Signaling in Angiogenesis and Tumorigenesis
(2009) · Advances in Cancer Research · doi:10.1016/s0065-230x(09)02002-8 · Cited by 620
Tabernero, J., Rojo, F., Calvo, E., Burris, H., Judson, I., Hazell, K., Martinelli, E., Cajal, S. R. Y., Jones, S., Vidal, L., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.5482 · Cited by 474
Targeting mammalian target of rapamycin (mTOR) for health and diseases
Tsang, C. K., Qi, H., Liu, L. F., & Zheng, X. F. S. (2007) · Drug Discovery Today · doi:10.1016/j.drudis.2006.12.008 · Cited by 406
A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas
Duran, I., Kortmansky, J., Singh, D., Hirte, H., Kocha, W., Goss, G., Le, L., Oza, A., Nicklee, T., Ho, J., et al. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603419 · Cited by 317
Metadata
- Authors
- Raymond, E., Alexandre, J., Faivre, S., Vera, K., Materman, E., Boni, J., Leister, C., Korth-Bradley, J., Hanauske, A., & Armand, J.-P.
- Venue
- Journal of Clinical Oncology
- Published
- 2004-06-15
- Volume
- 22
- Issue
- 12
- Pages
- 2336-2347
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2147394591
- Cited by
- 499
- References
- 37
- FWCI
- 13.45
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Safety and Pharmacokinetics of Escalated Doses of Weekly Intravenous Infusion of CCI-779, a Novel mTOR Inhibitor, in Patients With Cancer. https://app.cochat.ai/papers/10.1200/jco.2004.08.116
- The paper
- Raymond, E., Alexandre, J., Faivre, S., Vera, K., Materman, E., Boni, J., Leister, C., Korth-Bradley, J., Hanauske, A., & Armand, J.-P. (2004). Safety and Pharmacokinetics of Escalated Doses of Weekly Intravenous Infusion of CCI-779, a Novel mTOR Inhibitor, in Patients With Cancer. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2004.08.116
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
