HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Efficacy of the novel camptothecin gimatecan against orthotopic and metastatic human tumor xenograft models.

AbstractPURPOSE:
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:
The models include two orthotopic central nervous system tumors, two melanomas growing intracranially, and an ovarian carcinoma growing i.p. In addition, gimatecan was tested against experimental lung metastases of two tumor types (lung and ovarian carcinomas). Gimatecan was delivered by oral gavage according to various schedules (daily or intermittent). The time (in days) mice required to show evident signs of disease was used as end point for drug efficacy.
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.
AuthorsMichelandrea De Cesare, Graziella Pratesi, Silvia Veneroni, Raffaella Bergottini, Franco Zunino
JournalClinical 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
PMID15534112 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • ST 1481
  • Camptothecin
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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: