title: Hydroxyurea did not enhance the clinical response to vinblastine in patients with anthracycline-resistant metastatic breast cancer.
abstract: BACKGROUND
  Vinblastine is commonly used in metastatic breast cancer after anthracycline failure. The response rate to vinblastine is approximately 20%, with short duration of response. In vitro studies have shown that the addition of hydroxyurea resulted in increased accumulation of vinblastine in tumor cells and in loss of double minutes. We evaluated the combination of vinblastine and hydroxyurea in patients with anthracycline-resistant metastatic breast cancer.
  
  
  METHODS
  Fourteen assessable patients with metastatic breast cancer were entered in the study. All patients had progressed on anthracyclines or progressed within 8 months of stopping anthracyclines. Patients received hydroxyurea (500 mg orally) every Monday, Wednesday and Friday starting one week before the first course of chemotherapy and continuing throughout treatment until disease progression. Vinblastine (6 mg/m2) was given intravenously every 21 days,
  
  
  RESULTS
  The median number of courses for vinblastine was 3.5 (range, 1-6). Three patients had partial responses in soft tissue metastases (21%). Four patients had stable disease. Four patients had > grade 2 neutropenia, and 1 patient had grade 4 thrombocytopenia. There were 2 cases of grade 3 constipation, 2 of grade 3 nausea, and 1 each of grade 2 neuropathy and myalgia. There was no treatment-related mortality.
  
  
  CONCLUSIONS
  Low-dose hydroxyurea in combination with vinblastine has a 21% response rate in metastatic breast cancer after anthracycline failure. Toxicity was mild and generally reversible. At the adopted dose schedule of hydroxyurea, the antitumor activity of vinblastine in anthracycline-resistant metastatic breast cancer did not appear to be enhanced.
authors.affiliation: Division of Medical Oncology, Ottawa Regional Cancer Centre, Ontario, Canada.
authors.forename: S D
authors.initials: SD
authors.lastname: Huan
authors.forename: J C
authors.initials: JC
authors.lastname: Yau
authors.forename: E
authors.initials: E
authors.lastname: Tomiak
authors.forename: R
authors.initials: R
authors.lastname: Goel
authors.forename: C
authors.initials: C
authors.lastname: Cripps
authors.forename: S Z
authors.initials: SZ
authors.lastname: Gertler
authors.forename: I A
authors.initials: IA
authors.lastname: Prosser
authors.forename: D J
authors.initials: DJ
authors.lastname: Stewart
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D008875:Middle Aged; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D006918:Hydroxyurea