title: A Phase II study of intravenous exatecan mesylate (DX-8951f) administered daily for 5 days every 3 weeks to patients with metastatic breast carcinoma.
abstract: BACKGROUND
  The objective of the current study was to determine the antitumor activity, safety, and pharmacokinetic (PK) profile of exatecan mesylate in patients with anthracycline-resistant and taxane-resistant, metastatic breast carcinoma.
  
  
  METHODS
  All patients had clinical evidence of metastatic breast carcinoma; disease resistance or progression after chemotherapy that included anthracyclines and taxanes; no prior chemotherapy with camptothecin derivatives; and bidimensionally measurable disease. The starting dose of exatecan mesylate was either 0.5 mg/m(2) per day or 0.3 mg/m(2) per day, depending on prior chemotherapy exposure. PK blood samples were collected from each patient during the first course of therapy.
  
  
  RESULTS
  Thirty-nine patients received a total of 172 courses of therapy (median, 4 courses; range, 1-16 courses). Three patients (7.7%) had a partial response, and 20 patients (51.3%) had either a minor response or stable disease. Approximately 20% of patients had stable disease for 6 months or longer. The median time to disease progression was 3 months, and the median survival was 14 months. The most frequent severe adverse event was neutropenia. The most frequent severe (Grade 3-4) nonhematologic toxicities were fatigue, nausea, headache, myalgia, constipation, emesis, and paresthesias in 28%, 10%, 10%, 8%, 8%, 5%, and 5% of patients, respectively. Exatecan mesylate displayed linear PK characteristics at the doses administered. The average plasma clearance, total volume of distribution, and terminal elimination half-life were approximately 1.4 L per hour per m(2), 12 L/m(2), and 8 hours, respectively.
  
  
  CONCLUSIONS
  Exatecan mesylate had moderate activity in patients with anthracycline-refractory and taxane-refractory, metastatic breast carcinoma. The toxicity profile of exatecan mesylate was acceptable, and it appeared to have linear PK characteristics on the basis of multiple dose administration.
authors.affiliation: Department of Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 424, Houston, TX 77030, USA. festeva@mdanderson.org
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
authors.forename: Edgardo
authors.initials: E
authors.lastname: Rivera
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Melanie
authors.initials: M
authors.lastname: Royce
authors.forename: Anil
authors.initials: A
authors.lastname: Duggal
authors.forename: Philippe
authors.initials: P
authors.lastname: Colucci
authors.forename: Robert
authors.initials: R
authors.lastname: DeJager
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C095887:exatecan; D002166:Camptothecin