title: Gemcitabine and oxaliplatin in patients with metastatic breast cancer resistant to or pretreated with both anthracyclines and taxanes: clinical and pharmacokinetic data.
abstract: OBJECTIVE
  To evaluate the efficacy, the toxicity and the pharmacokinetics of a gemcitabine (GEM) and oxaliplatin (OXA) combination in metastatic breast cancer patients (MBC), previously treated with anthracycline and taxanes.
  
  
  METHODS
  A total of 40 women were enrolled; 37 patients had visceral metastases as dominant site of disease, including 20 patients with liver metastases and 14 with multiple visceral metastases. Three patients received neo-adjuvant chemotherapy, 13 patients adjuvant chemotherapy alone, 24 patients chemotherapy for MBC alone. Gemcitabine was given at 1000 mg/m2 on days 1, 8 followed by oxaliplatin at 100 mg/m2 iv on day 2 every 2 weeks (GEM-OXA sequence). Possible pharmacokinetic interactions were studied in 10 patients, by administering on cycle 1 gemcitabine d1/oxaliplatin d2 (GEM-OXA) and on cycle 2 oxaliplatin d1/gemcitabine d2 (OXA-GEM).
  
  
  RESULTS
  After a median of 8 cycles, 10 partial response (PR) (25%), 16 stable disease (SD) (40%), and 14 progressive disease (PD) (35%) were obtained. The median duration of response was 6 months (3-9) for responding patients and 4.9 months (2-7.5) for patients with stable disease. For PR, SD and PD patients, median survival was 18 (10-23+), 13 (8-18), and 6 months (4-13), respectively. G3-4 neutropenia occurred in 20% of patients (febrile G3 neutropenia in 2.5%), G3-4 thrombocytopenia and anemia in 15% and 7.5%. The most frequent G3-4 nonhematologic toxicity was represented by peripheral neuropathy (20%), always reversible. The GEM-OXA and OXA-GEM schedules showed a similar pharmacokinetic behavior, with no sequence-dependent interaction.
  
  
  CONCLUSIONS
  The combination gemcitabine plus oxaliplatin has moderate activity in anthracycline and taxanes resistant/relapsed heavily treated patients, mild toxicity and no administration sequence-dependent pharmacokinetic interactions.
authors.affiliation: Medical Oncology Department, San Giovanni Antica Sede Hospital, Torino, Italy. airoldim@yahoo.com
authors.forename: Mario
authors.initials: M
authors.lastname: Airoldi
authors.forename: Luigi
authors.initials: L
authors.lastname: Cattel
authors.forename: Roberto
authors.initials: R
authors.lastname: Passera
authors.forename: Fulvia
authors.initials: F
authors.lastname: Pedani
authors.forename: Laura
authors.initials: L
authors.lastname: Delprino
authors.forename: Caterina
authors.initials: C
authors.lastname: Micari
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D011446:Prospective Studies; D016019:Survival Analysis; D043823:Taxoids; D000093542:Gemcitabine
chemical_list: D018943:Anthracyclines; D009944:Organoplatinum Compounds; D043823:Taxoids; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000093542:Gemcitabine