Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Tortora, G.
Right arrow Articles by Bianco, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tortora, G.
Right arrow Articles by Bianco, A. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Annals of Oncology 13:392-398, 2002
© 2002 European Society for Medical Oncology

Preclinical and phase I study of oxaliplatin and topotecan in combination in human cancer

G. Tortora1,+, F. Ciardiello1, V. Damiano1, M. De Laurentiis1, E. Matano1, S. Pepe1, M. Pensabene1, G. Catalano2, S. De Placido1 and A. R. Bianco1

1Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università di Napoli Federico II, Napoli, Italy; 2Dipartimento di Medicina Sperimentale F. Magrassi, Seconda Universitá di Napoli, Napoli, Italy

Received 18 May 2001; revised 23 August 2001; accepted 6 September 2001.

Background

DNA damage caused by platinum agents is frequently followed by induction of topoisomerase I, providing a rationale for use of platinum-based compounds with topoisomerase I inhibitors.

Materials and methods

We studied the effect of a sequential schedule of oxaliplatin on day 1 and topotecan on days 2–5, in human colon and ovarian cancer cells in vitro, in nude mice bearing human cancer xenografts and finally in cancer patients in a phase I trial.

Results

We demonstrated a supra-additive effect of this combination on inhibition of colony formation and induction of apoptosis in vitro. We then demonstrated that the two agents in combination markedly inhibit tumor growth in nude mice. We translated these results into a clinical setting, conducting a phase I study in cancer patients with oxaliplatin 85 mg/m2 on day 1 and topotecan at doses escalating from 0.5 to 1.5 mg/m2 on days 2–5. Sixty cycles of treatment were administered to 18 patients affected prevalently by ovarian and colorectal cancer. Combination with topotecan 1.5 mg/m2 caused a dose-limiting toxicity. Therefore the maximum tolerated dose of topotecan was 1.25 mg/m2, at which six patients experienced a mild hematological and gastrointestinal toxicity. We also obtained evidence of clinical activity, particularly in ovarian cancer.

Conclusions

Our results provide a solid biological and clinical rationale for a phase II trial at the recommended doses of oxaliplatin 85 mg/m2 and topotecan 1.25 mg/m2, possibly in ovarian cancer patients.

Key words: ovarian cancer, oxaliplatin, phase I, topotecan


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.