title: Single-agent estramustine phosphate (EMP) is active in advanced breast cancer after failure with anthracyclines and taxanes.
abstract: OBJECTIVE
  Estramustine phosphate (EMP) is an oral cytotoxic agent that depolymerizes tubuline, a mechanism of action that has been revisited during the last decade. Because of its lack of haematological toxicity and favourable tolerance profile, EMP is a good candidate for palliative chemotherapy. The aim of the study was to assess its tolerance and efficacy in advanced breast cancer after failure with usual regimens.
  
  
  METHODS
  Patients with a life expectancy of at least 12 weeks and bi-dimensionally measurable disease having received at least 1 line of chemotherapy (including taxanes and/or anthracyclines) for advanced breast cancer (ABC) were eligible. EMP was given daily at a dose of 10 mg/kg until disease progression, unacceptable toxicity or patient refusal to continue chemotherapy.
  
  
  RESULTS
  Forty patients were included between June 1998 and December 1999. Patients had previously received one to eight chemotherapy regimens (median is two) for ABC. Twenty-two patients (55%) had visceral involvement and eighteen patients (45%) had osseous, chest wall or soft tissue metastases. Adverse events leading to early interruption of EMP were grade 2 allergy (n = 1), grade 2-3 nausea (n = 6), deep-vein thrombosis (n = 1), grade 3 sepsis (n = 1). One patient died at twenty-four weeks from pulmonary embolism, and another at fourteen weeks from unknown cause. Seven objective responses were observed (17.5%; 95% confidence interval (CI): 6%-30%). Median time to failure was 24 weeks (14-52+) in responding patients. All objective responses but one were observed in patients with visceral metastases. In 10 other patients (25%), disease remained stable with a median time to failure of 27 weeks (16-50); 6 of these experienced a decrease of consumption of analgesics or an improvement of performance status.
  
  
  CONCLUSIONS
  EMP is an active drug in ABC after failure with taxanes and anthracyclines, whose tolerance profile appears favourable.
authors.affiliation: Department of Medicine, Institut Gustave-Roussy, Villejuif, France. laurent.zelek@aero-eu.org
authors.forename: L
authors.initials: L
authors.lastname: Zelek
authors.forename: S
authors.initials: S
authors.lastname: Barthier
authors.forename: M
authors.initials: M
authors.lastname: Riofrio
authors.forename: D
authors.initials: D
authors.lastname: Sevin
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
authors.forename: M
authors.initials: M
authors.lastname: Spielmann
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D016879:Salvage Therapy; D043823:Taxoids; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; D004961:Estramustine