Open Access Research article

Weekly paclitaxel plus trastuzumab in metastatic breast cancer pretreated with anthracyclines-a phase II multipractice study

Matthias John1*, Axel Hinke2, Martina Stauch3, Heiner Wolf4, Benno Mohr5, Hans-Joachim Hindenburg6, Jens Papke7, Joachim Schlosser8 and for the FAKT Study Group

Author Affiliations

1 Practice for Gynecology, Dr.-Doerffel-Strasse 1, 08371, Glauchau, Germany

2 WiSP Research Institute, Karl-Benz-Str. 1, 40764, Langenfeld, Germany

3 Practice for Medical Oncology, Niederbonner Arnoldstrasse 2, 96317, Kronach, Germany

4 Practice for Medical Oncology, Arnoldstrasse 18, 01307, Dresden, Germany

5 Practice for Medical Oncology, Breite Strasse 52, 13597, Berlin, Germany

6 Practice for Medical Oncology, Pichelsdorfer Str. 105, 13595, Berlin, Germany

7 Praxis for Medical Oncology, Rosa-Luxemburg-Strasse 6, 01844, Neustadt/Sachsen, Germany

8 Practice for Gynecology, Clausstrasse 76-80, 09126, Chemnitz, Germany

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BMC Cancer 2012, 12:165  doi:10.1186/1471-2407-12-165

Published: 4 May 2012

Abstract

Background

The 3-weekly combination of trastuzumab and paclitaxel has been approved for the treatment of advanced breast cancer based on a large pivotal study. However, mono and combination chemotherapy trials suggest that weekly paclitaxel has a better therapeutic index, especially in the palliative setting. The present trial examined the efficacy and safety of weekly paclitaxel over a limited duration combined with continued trastuzumab in HER2+ patients.

Methods

Patients with histologically confirmed metastatic breast cancer overexpressing HER2 were eligible if pretreated with anthracycline in either the adjuvant or palliative setting. Treatment consisted of weekly trastuzumab (2 mg/kg/week for up to one year after a loading dose of 4 mg/kg in week 1) and paclitaxel (90 mg/m², administered in weeks 1–6 and 8–13).

Results

Twenty-seven German centers enrolled 121 patients. The median number of metastatic sites was two (range 1–5); 38% of patients had received chemotherapy for advanced disease. After a median 42 weeks of trastuzumab treatment, limited by disease progression in roughly half the patients, a best objective response rate (complete response + partial response) of 76% was achieved, including complete remissions in 29%. 74% of patients lived without tumor progression at six months. Median progression-free and overall survival were 9.4 (95% confidence interval [CI]: 8.1–11.3) and 22 months (95% CI: 17–46). After alopecia, Common Toxicity Criteria grade ≥2 toxicity was predominantly hematological (leukopenia [31%] and anemia [41%]); however, thrombocytopenia occurred in only 5%. Neurotoxicity was remarkably low. Two cardiac events (grades 2 and 3) were presumed treatment-related.

Conclusions

Weekly paclitaxel plus trastuzumab allows an increased dose density and offers an attractive and effective alternative to the conventional schedule. Limiting the duration of cytotoxic therapy to 3 months seems to be an option to reduce neurotoxicity without impairing long-term outcome.