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

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.

• Authors: Matthias John, Axel Hinke, Martina Stauch, Heiner Wolf, Benno Mohr, Hans-Joachim Hindenburg, Jens Papke, Joachim Schlosser, FAKT Study Group
• Journal: BMC cancer (BMC Cancer) Vol. 12 Pg. 165 (May 04 2012) ISSN: 1471-2407 [Electronic] England
• PMID: 22559145 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Trastuzumab
• Paclitaxel

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Breast Neoplasms (drug therapy, mortality, pathology)
• Disease Progression
• Female
• Humans
• Middle Aged
• Neoplasm Grading
• Neoplasm Metastasis
• Neoplasm Staging
• Paclitaxel (administration & dosage)
• Prognosis
• Trastuzumab
• Treatment Outcome