Skip Navigation


Annals of Oncology Advance Access originally published online on April 11, 2008
Annals of Oncology 2008 19(8):1417-1422; doi:10.1093/annonc/mdn154
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
19/8/1417    most recent
mdn154v1
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 arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Mrozek, E.
Right arrow Articles by Shapiro, C. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mrozek, E.
Right arrow Articles by Shapiro, C. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

breast cancer

Phase II study of sequentially administered low-dose mitomycin-C (MMC) and irinotecan (CPT-11) in women with metastatic breast cancer (MBC)

E. Mrozek1,2,*, J. Kolesar3, D. Young4, J. Allen2,5, M. Villalona-Calero1 and C. L. Shapiro1,2

1 Division of Hematology and Oncology, Ohio State University Medical Center, Columbus, Beijing Cancer Hospital and Institute, Peking University School of Oncology, Beijing
2 Comprehensive Breast Health Services, Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus
3 School of Pharmacy, University of Wisconsin, Madison
4 Center for Biostatistics, Comprehensive Cancer Center, The Ohio State University, Columbus
5 Clinical Trials Office, Comprehensive Cancer Center, Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, USA

* Correspondence to: Dr E. Mrozek, Division of Hematology and Oncology and Comprehensive Breast Health Services, Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, 320 West 10th Avenue, Columbus, OH 43210, USA. Tel: +1 614-293-6453; Fax: +1 614-293-7529; E-mail: ewa.mrozek{at}osumc.edu

Background: Preclinical studies show that mitomycin-C (MMC) followed by irinotecan (CPT-11) is synergistic. Therefore, we evaluated the toxicity and efficacy of sequentially administered low-dose MMC and CPT-11 in patients (pts) with pretreated metastatic breast cancer (MBC). Secondary objective was to evaluate the correlation between MMC-induced topoisomerase I (TOPO I) expression and NAD(P)H:quinone oxireductase 1 (NQO1) genotypes in peripheral blood mononuclear cells (PBMC) and efficacy or toxicity of the regimen.

Design: Thirty-two pts received MMC i.v. 6 mg/m2 day 1 and CPT-11 i.v. 125 mg/m2 days 2 and 8 every 28 days for maximum of six cycles. TOPO I expression and NQO1 reductase genotyping in 23 of 32 (72%) pts were assayed by PCR.

Results: The median time to progression (TTP) was 4.7 months (95% confidence interval 4.0–5.4 months). TOPO I expression was increased 5- to 10-fold and 20- to 30-fold in PBMC at 24 and 168 h, respectively. There was no relationship between these markers and efficacy or toxicity of the regimen.

Conclusions: Sequential low-dose MMC and CPT-11 was active and tolerable by pretreated MBC pts. Future trials should focus on less pretreated MBC pts and sequential tumor biopsies to test the hypothesis that increased intratumoral expression of TOPO I is related to efficacy.

Key words: breast cancer, irinotecan, mitomycin, topoisomerase I

Received for publication October 14, 2007. Revision received February 24, 2008. Accepted for publication March 10, 2008.


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.