Cancer Chemotherapy and Pharmacology

, Volume 64, Issue 2, pp 407–412 | Cite as

Dose-finding study of weekly docetaxel, epirubicin and capecitabine, as first-line treatment in advanced breast cancer

  • S. H. Waters
  • A. Gillibrand
  • H. Berry
  • S. Kumar
  • G. Velikova
  • D. J. Dodwell
  • Timothy J. PerrenEmail author
Clinical Trial Report



Combinations of anthracycline, taxane and fluoropyrimidine are highly active in advanced breast cancer (ABC). In a phase II study of epirubicin 50 mg/m2, docetaxel 75 mg/m2, and infusional 5-FU 200 mg/m2/day, we found dose-limiting neutropenia and frequent central venous catheter complications. An alternative approach has been tested using weekly fractionation of docetaxel, and oral capecitabine.


Initially, six women with ABC were treated with epirubicin 60 mg/m2 day 1, docetaxel 25 mg/m2 days 1,8,15, and capecitabine 1,000 mg/m2 twice daily days 1–14, every 21 days. Six further patients received the above with capecitabine escalated to 1,500 mg/m2


Four DLTs occurred in six patients at the second dose level (febrile neutropenia in 2). There were frequent dose delays/reductions, and fatigue, nausea/vomiting, and diarrhoea were common. Overall, six of ten assessable patients achieved a partial response.


An active regimen, but significant haematological toxicity precluded dose further escalation.


Anthracyclines Antineoplastic combined chemotherapy protocols Breast neoplasms Capecitabine Taxoids 



We would like to thank the research team at St James’s and Cookridge Hospitals for their help with treatment and the majority of the data collection, in particular the data manager Tahira Khan. We acknowledge the ongoing support of Cancer Research UK for salary and infrastructure support of the research team. Financial support for the study was provided by Aventis and F. Hoffmann-La Roche. The above took no part in the collection, analysis and interpretation of data; nor in the decision to submit the manuscript for publication. The protocol was investigator led and initiated, with input from Aventis and F. Hoffmann-La Roche, who also reviewed the manuscript.

Conflict of interest statement

D. Dodwell and T. Perren have received honoraria for advisory work and speaking engagements from Aventis and F. Hoffmann-La Roche, and S.Waters has received training funded by F. Hoffmann-La Roche.

Supplementary material

280_2009_1021_MOESM1_ESM.doc (46 kb)
Supplementary material 1 (DOC 46 kb)


  1. 1.
    Smith IE, A’Hern RP, Coombes GA et al (2004) A novel continuous infusional 5-fluorouracil-based chemotherapy regimen compared with conventional chemotherapy in the neo-adjuvant treatment of early breast cancer: 5 year results of the TOPIC trial. Ann Oncol 15:751–758PubMedCrossRefGoogle Scholar
  2. 2.
    Humphreys AC, Dent J, Rodwell S et al (2004) Phase II study of docetaxel in combination with epirubicin and protracted venous infusion 5-fluorouracil (ETF) in patients with recurrent or metastatic breast cancer. A Yorkshire breast cancer research group study. Br J Cancer 90:2131–2134PubMedGoogle Scholar
  3. 3.
    Greco FA (1999) Docetaxel (Taxotere) administered in weekly schedules. Semin Oncol 26:28–31PubMedGoogle Scholar
  4. 4.
    Hainsworth JD, Burris HA 3rd, Erland JB et al (1998) Phase I trial of docetaxel administered by weekly infusion in patients with advanced refractory cancer. J Clin Oncol 16:2164–2168PubMedGoogle Scholar
  5. 5.
    Hainsworth JD, Burris HA 3rd, Greco FA (1999) Weekly administration of docetaxel (Taxotere): summary of clinical data. Semin Oncol 26:19–24PubMedGoogle Scholar
  6. 6.
    Belotti D, Vergani V, Drudis T et al (1996) The microtubule-affecting drug paclitaxel has antiangiogenic activity. Clin Cancer Res 2:1843–1849PubMedGoogle Scholar
  7. 7.
    Nadella P, Shapiro C, Otterson GA et al (2002) Pharmacobiologically based scheduling of capecitabine and docetaxel results in antitumor activity in resistant human malignancies. J Clin Oncol 20:2616–2623PubMedCrossRefGoogle Scholar
  8. 8.
    Sawada N, Ishikawa T, Fukase Y et al (1998) Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res 4:1013–1019PubMedGoogle Scholar
  9. 9.
    Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41PubMedCrossRefGoogle Scholar
  10. 10.
    Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216PubMedCrossRefGoogle Scholar
  11. 11.
    O’Shaughnessy J, Miles D, Vukelja S et al (2002) Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 20:2812–2823PubMedCrossRefGoogle Scholar
  12. 12.
    Beslija S, Obralic N, Basic H et al (2006) Randomized trial of sequence vs. combination of capecitabine (X) and docetaxel (T): XT vs. T followed by X after progression as first-line therapy for patients (pts) with metastatic breast cancer (MBC). J Clin Oncol 24: Suppl 18S, abstract 571Google Scholar
  13. 13.
    Soto C, Torrecillas L, Reyes S et al (2006) Capecitabine (X) and taxanes in patients (pts) with anthracycline-pretreated metastatic breast cancer (MBC): sequential vs. combined therapy results from a MOSG randomized phase III trial. J Clin Oncol 24: Suppl 18S, abstract 570Google Scholar
  14. 14.
    Pagani O, Sessa C, Nole F et al (2005) Dose-finding study of weekly docetaxel, anthracyclines plus fluoropyrimidines as first-line treatment in advanced breast cancer. Ann Oncol 16:1609–1617PubMedCrossRefGoogle Scholar
  15. 15.
    Venturini M, Durando A, Garrone O et al (2003) Capecitabine in combination with docetaxel and epirubicin in patients with previously untreated, advanced breast carcinoma. Cancer 97:1174–1180PubMedCrossRefGoogle Scholar
  16. 16.
    Mansutti M, Fasola G, Cavazzini G et al (2004) Randomized phase III trial comparing TEX (docetaxel, epirubicin and capecitabine) vs. TE (docetaxel, epirubicin) in advanced breast cancer patients: findings from the 2nd interim analysis. Ann Oncol 15:iii42 (abstract 157P)Google Scholar
  17. 17.
    Wenzel C, Bartsch R, Locker GJ et al (2005) Preoperative chemotherapy with epidoxorubicin, docetaxel and capecitabine plus pegfilgrastim in patients with primary breast cancer. Anticancer Drugs 16:441–445PubMedCrossRefGoogle Scholar
  18. 18.
    Tannock IF, de Wit R, Berry WR et al (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502–1512PubMedCrossRefGoogle Scholar
  19. 19.
    Di Maio M, Perrone F, Chiodini P et al (2007) Individual patient data meta-analysis of docetaxel administered once every 3 weeks compared with once every week second-line treatment of advanced non-small-cell lung cancer. J Clin Oncol 25:1377–1382PubMedCrossRefGoogle Scholar
  20. 20.
    Di Costanzo F, Gasperoni S, Papaldo P et al (2006) Weekly paclitaxel plus capecitabine in advanced breast cancer patients: dose-finding trial of GOIRC and GOL. Ann Oncol 17:79–84PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • S. H. Waters
    • 1
  • A. Gillibrand
    • 1
  • H. Berry
    • 1
  • S. Kumar
    • 1
  • G. Velikova
    • 1
  • D. J. Dodwell
    • 1
  • Timothy J. Perren
    • 1
    Email author
  1. 1.St James’s Institute of OncologyLeedsUK

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