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01-08-2012 | Clinical Trial Report

Metronomic oral combination chemotherapy with capecitabine and cyclophosphamide: a phase II study in patients with HER2-negative metastatic breast cancer

Authors: Masataka Yoshimoto, Shintaro Takao, Masaru Hirata, Yasushi Okamoto, Sumio Yamashita, Yoshihiro Kawaguchi, Makoto Takami, Hidemi Furusawa, Satoshi Morita, Chigusa Abe, Junichi Sakamoto

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2012

Abstract

Purpose

Metronomic combination chemotherapy with the oral fluoropyrimidine doxifluridine/5′-deoxy-5-fluorouridine (5 -DFUR) and oral cyclophosphamide (C) showed promising efficacy in a single-arm study. The oral fluoropyrimidine capecitabine was designed to deliver 5-fluorouracil preferentially to tumors, potentially improving efficacy over doxifluridine. We conducted a phase II multicenter study to evaluate an all-oral XC combination in patients with HER2-negative metastatic breast cancer (MBC).

Materials and methods

Patients received capecitabine 828 mg/m² twice daily with cyclophosphamide 33 mg/m² twice daily, days 1–14 every 3 weeks. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.

Results

Between May 2007 and April 2009, 51 patients were enrolled and 45 were included in the efficacy analysis. The median follow-up was 18.1 months. ORR was 44.4% and stable disease (≥24 weeks) was achieved in 13.4%, resulting in a 57.8% clinical benefit response rate. Median PFS was 12.3 months (95% confidence interval: 8.9–18.9 months). Median PFS was 10.7 months in triple-negative disease and 13.2 months in estrogen-receptor positive, HER2-negative disease. The 1- and 2-year OS rates were 86 and 71%, respectively. Median OS has not been reached. Grade 3 adverse events comprised leukopenia (26%), neutropenia (16%), and decreased hemoglobin (2%). There was no grade 3 hand-foot syndrome.

Conclusions

Oral XC is an effective first- or second-line therapy for MBC, demonstrating high activity in both luminal A and triple-negative disease with few severe side effects. This metronomic oral combination chemotherapy could be beneficial for the treatment of HER2-negative MBC.

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Title: Metronomic oral combination chemotherapy with capecitabine and cyclophosphamide: a phase II study in patients with HER2-negative metastatic breast cancer
Authors: Masataka Yoshimoto
Shintaro Takao
Masaru Hirata
Yasushi Okamoto
Sumio Yamashita
Yoshihiro Kawaguchi
Makoto Takami
Hidemi Furusawa
Satoshi Morita
Chigusa Abe
Junichi Sakamoto
Publication date: 01-08-2012
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 2/2012
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-012-1826-x

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