title: Evidence for in vivo synergism between docetaxel and gemcitabine in patients with metastatic breast cancer.
abstract: BACKGROUND
  The docetaxel and gemcitabine combination is active as salvage therapy in taxane-resistant/refractory patients with metastatic breast cancer (MBC). We conducted a phase II study to determine if this activity is due to an in vivo synergistic effect.
  
  
  METHODS
  Women with measurable MBC, who were refractory or resistant to docetaxel monotherapy as first- or second-line treatment, were enrolled. Patients with progressive disease (PD) or stable disease (SD) after receiving at least four cycles of docetaxel received gemcitabine 900 mg/m(2) on days 1 and 8 plus docetaxel 100 mg/m(2 )on day 8, every 3 weeks. Granulocyte colony-stimulating factor could be used prophylactically in patients who experienced grade 3/4 neutropenia after the first cycle.
  
  
  RESULTS
  Between January 1999 and March 2002, 173 courses of docetaxel and gemcitabine were administered to 50 patients. The median number of metastatic sites was two (range one to three). Forty-six percent of patients responded (three complete responses, 20 partial responses), whereas 28% had SD and 26% had PD. The median duration of response was 6.1 +/- 2.4 months. The median time to disease progression was 7.5 months (range 1-25) and the overall median survival was 15 months (range 3-57). Neutropenia was the only National Cancer Institute Common Toxicity Criteria grade 4 toxicity (in seven patients). Hematological grade 3 toxicities included neutropenia in 12 patients, thrombocytopenia in seven and anemia in one, while non-hematological toxicities were mild and manageable.
  
  
  CONCLUSIONS
  The high overall response rate of the docetaxel plus gemcitabine combination after docetaxel failure in patients with MBC can be attributed to an in vivo synergism between the two drugs. These data warrant confirmation in a randomized study.
authors.affiliation: 1st Department of Medical Oncology, St Savvas Anticancer-Oncologic Hospital, Athens, Greece. empika@ath.forthnet.gr
authors.forename: A
authors.initials: A
authors.lastname: Alexopoulos
authors.forename: D
authors.initials: D
authors.lastname: Tryfonopoulos
authors.forename: M V
authors.initials: MV
authors.lastname: Karamouzis
authors.forename: G
authors.initials: G
authors.lastname: Gerasimidis
authors.forename: I
authors.initials: I
authors.lastname: Karydas
authors.forename: K
authors.initials: K
authors.lastname: Kandilis
authors.forename: J
authors.initials: J
authors.lastname: Stavrakakis
authors.forename: H
authors.initials: H
authors.lastname: Stavrinides
authors.forename: C
authors.initials: C
authors.lastname: Georganta
authors.forename: A
authors.initials: A
authors.lastname: Ardavanis
authors.forename: G
authors.initials: G
authors.lastname: Rigatos
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000093542:Gemcitabine