Abstract | PURPOSE:
Gimatecan, a novel oral lipophilic camptothecin characterized by favorable features at molecular/cellular level and by a promising profile of preclinical activity, is currently in clinical phase I/II. The aim of the study was to additionally investigate the therapeutic potential of the drug in human tumor xenografts growing in different organs as models representative of tumor growth in the clinical setting. EXPERIMENTAL DESIGN: RESULTS:
Gimatecan was highly effective in delaying disease manifestations in all tumor systems investigated. In the intracranially growing tumors, a significant time increase (versus control mice) was achieved by the drug administered according to all of the schedules. In addition, almost all treated mice were alive and tumor-free at the end of the experiment in the metastatic models and in the ascitic ovarian tumor. The daily prolonged treatment schedule was the best one. CONCLUSIONS: In all tumor systems investigated, including orthotopic tumor growth models and lung metastases, the oral administration of gimatecan showed a therapeutic benefit in terms of survival increase. The good oral availability allowed a prolonged daily treatment regimen, which seems the most promising to exploit the therapeutic potential of the drug.
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Authors | Michelandrea De Cesare, Graziella Pratesi, Silvia Veneroni, Raffaella Bergottini, Franco Zunino |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 10
Issue 21
Pg. 7357-64
(Nov 01 2004)
ISSN: 1078-0432 [Print] United States |
PMID | 15534112
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Animals
- Brain
(pathology)
- Camptothecin
(analogs & derivatives, pharmacology)
- Female
- Humans
- Melanoma
(drug therapy)
- Mice
- Mice, Nude
- Neoplasm Metastasis
- Neoplasm Transplantation
- Neoplasms, Experimental
(drug therapy)
- Nervous System Neoplasms
(drug therapy)
- Ovarian Neoplasms
(drug therapy)
- Time Factors
- Xenograft Model Antitumor Assays
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