Cancer Chemotherapy and Pharmacology

, Volume 81, Issue 2, pp 365–372 | Cite as

CYP1A1 genetic polymorphism is a promising predictor to improve chemotherapy effects in patients with metastatic breast cancer treated with docetaxel plus thiotepa vs. docetaxel plus capecitabine

  • Xinna Zhou
  • Guoliang Qiao
  • Xiaoli Wang
  • Qingkun Song
  • Michael A. Morse
  • Amy Hobeika
  • William R. Gwin
  • Jun RenEmail author
  • H. Kim LyerlyEmail author
Original Article



A prospective study was performed to compare the outcome for metastatic breast cancer (MBC) patients treated with docetaxel plus thiotepa (DT) or docetaxel plus capecitabine (DC), and to explore the value of CYP1A1*2C polymorphisms in predicting clinical efficacy of these chemotherapies.


MBC patients (n = 130) were randomized to treatment with DT (n = 65) or DC (n = 65). Response rate, disease control rate, progression-free and overall survival were monitored. Genotyping of CYP1A1*2C was performed in all patients.


DT and DC produced similar overall disease control rates (76.9 vs 69.2%), median PFS (6.7 vs. 7.5 months) and OS (20.1 vs. 21.0 months) (P > 0.05 for all comparisons); however, DT exhibited a higher rate of control of localized liver metastases (78.6 vs 41.2%, P = 0.023). Among patients homozygous for wild-type CYP1A1*1 genotype (AA), DT treatment was associated with a significantly longer PFS (8.4 vs. 6.4 months, P = 0.019) and OS (33.4 vs. 15.8 months, P = 0.018). Conversely, among patients carrying the variant CYP1A1*2C genotype (AG/GG), DC treatment was associated with a significantly longer PFS (8.4 vs. 5.5 month, P = 0.005), and OS (28.5 vs. 19.6 months, P = 0.010). After adjusting for competing risk factors, CYP1A1*2C genotype was confirmed to be an independent predictor of PFS and OS for each chemotherapy combination.


Overall, DT and DC result in similar clinical efficacy for MBC patients; however, efficacy for each therapy differs depending on CYP1A1*2C genotype.


CYP1A1 Single nucleotide polymorphism Breast cancer Liver metastasis Docetaxel Thiotepa Capecitabine 


Compliance with ethical standards


This study was funded by Susan G Komen for Cure Foundation (no. SPCHIN1201), Youth Foundation of Beijing Shijitan Hospital of Capital Medical University (no. 2013-q-04) and China Railway Corporation Research Project (2016-A44).

Conflict of interest

The authors declared that they have no conflicts of interest related to this work.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

280_2017_3500_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 13 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer VaccinesCapital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical UniversityBeijingChina
  2. 2.Department of Medical OncologyKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital and Institute, Peking University School of OncologyBeijingChina
  3. 3.Department of MedicineDuke University Medical CenterDurhamUSA
  4. 4.Department of SurgeryDuke University Medical CenterDurhamUSA
  5. 5.Department of MedicineUniversity of WashingtonSeattleUSA

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