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Vinorelbine and capecitabine in anthracycline- and/or taxane-pretreated metastatic breast cancer: sequential or combinational?

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Abstract

Purpose

The difference between combinational and pre-planned sequential therapies using regimens that include non-anthracycline and taxane in the first-line setting remains unclear. The purpose of this study is to explore the interaction between vinorelbine (N) and capecitabine (X) in breast cancer cells and to compare the simultaneous or sequential administration of the two drugs in patients with metastatic breast cancer (MBC) as first-line treatment.

Methods

First, we explored the effects of vinorelbine on thymidine phosphorylase (TP) and thymidylate synthase (TS) expression in breast cancer cells. Next, we designed a prospective randomized phase II trial of MBC patients comparing the combinational and pre-planned sequential administration of vinorelbine and capecitabine in the first-line metastatic setting. The primary end point was progression-free survival (PFS). The correlation between clinical characteristics and class III β-tubulin expression and patient survival was also explored.

Results

Vinorelbine upregulates TP and downregulates TS in breast cancer cells, thereby further sensitizing tumor cells to capecitabine, which indicated the proper order for sequential therapy should be N → X. Sixty patients were eligible for the phase II trial. No significant difference was observed between the combinational arm and the sequential arm in terms of progression-free survival (PFS), overall response rate (ORR), and overall survival (OS). Only in the subgroup of patients with liver metastases were median PFS and OS significantly prolonged in the combinational arm (8.5 vs. 6.4 months, P = 0.041 and 23.8 vs. 13.9 months, P = 0.028, respectively). No association between class III β-tubulin expression and patient outcome was identified. Grade 3/4 adverse events were more common in the combinational arm.

Conclusions

Both the NX regimen and pre-planned sequential N → X regimen are acceptable as first-line treatments with comparable efficacies for MBC patients previously treated with anthracyclines and/or taxanes. Sequential monotherapies are recommended as the preferred approach to first-line chemotherapy for most MBC patients in the absence of an imminent visceral crisis and the need for rapid symptom and/or disease control.

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Authors and Affiliations

  1. Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China

    Jian Zhang, Shi-Yang Gu, Zhong-Hua Wang, Bi-Yun Wang, Hai-Yi Guo, Jia-Lei Wang, Lei-** Wang, **n-Min Zhao & **-Chun Hu

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Jian Zhang, Shi-Yang Gu, Zhong-Hua Wang, Bi-Yun Wang, Hai-Yi Guo, Jia-Lei Wang, Lei-** Wang, **n-Min Zhao & **-Chun Hu

  3. Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Yu Gan

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Supplementary material 1 (DOCX 21 kb)

280_2012_1983_MOESM2_ESM.docx

Supplemental figure 1. Representative images of class III β-tubulin expression. (A) High expression; (B) Low expression. (original magnification: ×200) (DOCX 775 kb)

280_2012_1983_MOESM3_ESM.tif

Supplemental figure 2. The diagram that vinorelbine can upregulate thymidine phosphorylase (TP) and downregulate thymidylate synthase (TS) in breast cancer cells (TIFF 1391 kb)

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Zhang, J., Gu, SY., Gan, Y. et al. Vinorelbine and capecitabine in anthracycline- and/or taxane-pretreated metastatic breast cancer: sequential or combinational?. Cancer Chemother Pharmacol 71, 103–113 (2013). https://doi.org/10.1007/s00280-012-1983-y

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