title: 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.affiliation: Practice for Gynecology, Dr.-Doerffel-Strasse 1, 08371 Glauchau, Germany. dr.matthias.john@web.de
authors.forename: Matthias
authors.initials: M
authors.lastname: John
authors.forename: Axel
authors.initials: A
authors.lastname: Hinke
authors.forename: Martina
authors.initials: M
authors.lastname: Stauch
authors.forename: Heiner
authors.initials: H
authors.lastname: Wolf
authors.forename: Benno
authors.initials: B
authors.lastname: Mohr
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Hindenburg
authors.forename: Jens
authors.initials: J
authors.lastname: Papke
authors.forename: Joachim
authors.initials: J
authors.lastname: Schlosser
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068878:Trastuzumab; D017239:Paclitaxel