Gefitinib (ZD1839) combined with weekly epirubicin in patients with metastatic breast cancer: A phase I study with biological correlate

G. Gasparini, R. Sarmiento, S. Amici, R. Longo, D. Gattuso, M. Zancan, M. Gion

Research output: Contribution to journalArticlepeer-review


Purpose: Epidermal growth factor receptor (EGFR) is overexpressed in approximately 50% of invasive breast carcinomas and it is correlated with hormone resistance and poor prognosis. EGFR suppression by gefitinib, a quinazoline derivative that inhibits phosphorylation of the specific receptor, represents a novel therapeutic strategy. A dose-finding study was performed to evaluate the combination of gefitinib with weekly epirubicin in patients with pretreated metastatic breast cancer. Methods: Fifteen patients were enrolled at four sequential dose levels. Gefitinib was administered orally, at the fixed daily dose of 250 mg. The starting dose of epirubicin was 20 mg/m2. Escalating dose levels of epirubicin were planned by increments of 5 mg/m2 per level, up to the maximum tolerated dose (MTD). Pharmacodynamic studies were performed by determining serum and tissue ERBB2 and EGFR. Results: At the first three dose levels tested no patient experienced a dose-limiting toxicity (DLT). In cohort 4, two patients experienced DLTs (grade 4 dyspnea and asthenia, grade 3 diarrhea and thrombocytopenia) identifying the MTD of epirubicin as 35 mg/m2. Of the 14 cases assessable for response, partial response was documented in two patients, and stable disease in seven, giving an overall disease control rate of 64.2%. The comparison of pre- and post-therapy ERBB2 and EGFR values was not statistically significant between the subgroups of patients regarding responsiveness to treatment. Conclusions: The recommended dose of epirubicin for phase II studies is 30 mg/m2 in combination with gefitinib at the daily dose of 250 mg. Pharmacodynamic studies did not identify any biomarker predictive of response.

Original languageEnglish
Pages (from-to)1867-1873
Number of pages7
JournalAnnals of Oncology
Issue number12
Publication statusPublished - Dec 2005


  • Breast cancer
  • Epirubicin
  • Gefitinib
  • Phase I study

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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