Annals of Oncology Advance Access originally published online on July 19, 2005
Annals of Oncology 2005 16(10):1624-1631; doi:10.1093/annonc/mdi321
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© 2005 European Society for Medical Oncology
Primary chemotherapy with gemcitabine as prolonged infusion, non-pegylated liposomal doxorubicin and docetaxel in patients with early breast cancer: final results of a phase II trial
1 Medizinische Klinik mit Schwerpunkt Onkologie und Hämatologie, Charité Campus Mitte, Humboldt Universität zu Berlin, Berlin; 2 Frauenklinik, Oskar-Ziethen-Krankenhaus, Berlin; 3 Frauenklinik, Universitätsklinikum Ulm, Ulm; 4 Klinik für Gynäkologie und Geburtshilfe, Charité Campus Mitte, Humboldt Universität zu Berlin, Berlin; 5 Department for Intelligent Systems, University of Bremen, Bremen; 6 Department of Pathology, University of Halle, Halle, Germany
* Correspondence to: Dr P. Schmid, Department of Oncology and Hematology, Charité Campus Mitte, Humboldt University Berlin, Schumannstr. 20/21, 10117 Berlin, Germany. Tel: +49-30-450-613005; Fax: +49-30-450-513952; E-mail: peter.schmid{at}charite.de
Background: Combinations of anthracyclines, taxanes and gemcitabine have shown high activity in breast cancer. This trial was designed to evaluate a modified combination regimen as primary chemotherapy. Non-pegylated liposomal doxorubicin (NPLD) was used instead of conventional doxorubicin to improve cardiac safety. Gemcitabine was given 72 h after NPLD and docetaxel as a prolonged infusion over 4 h in order to optimize synergistic effects and accumulation of active metabolites.
Patients and methods: Forty-four patients with histologically confirmed stage II or III breast cancer were treated with NPLD (60 mg/m2) and docetaxel (75 mg/m2) on day 1 and gemcitabine as 4-h infusion (350 mg/m2) on day 4. Treatment was repeated every 3 weeks for a maximum of six cycles. All patients received prophylactically recombinant granulocyte colony-stimulating factor. Patients with axillary lymph node involvement after primary chemotherapy received adjuvant treatment with cyclophosphamide, methotrexate and fluorouracil.
Results: The clinical response rate was 80%, and complete remissions of the primary tumor occurred in 10 patients (25%). Breast conservation surgery was performed in 19 out of 20 patients (95%) with an initial tumor size of less than 3 cm and in 14 patients (70%) with a tumor size 
3 cm. Seven patients had histologically confirmed complete responses accounting for a pCR rate of 17.5%. Expression of Ki-67 was the most important predictive parameter for response with high 38.9% breast pCR rate in patients with elevated Ki-67 expression. Although the predominant toxicity was myelosuppression with grade 3/4 neutropenia in 61% of patients few neutropenic complications resulted. Non-hematological toxicity was generally moderate with grade 3 or 4 toxicity in 10.0% of cycles. Most common non-hematologic toxicities were nausea, vomiting, alopecia, mucositis, asthenia and elevation of liver enzymes.
Conclusion: The evaluated schedule provides a safe and highly effective combination treatment for patients with early breast cancer, which is suitable for phase III studies.
Key words: adjuvant treatment, docetaxel, gemcitabine, liposomal doxorubicin, locally advanced breast cancer, neoadjuvant treatment, primary chemotherapy