title: Minimal clinical benefit of single agent Orathecin (Rubitecan) in heavily pretreated metastatic breast cancer.
abstract: OBJECTIVE
  The purpose of this phase II study was to evaluate the efficacy and tolerability of Orathecin, an oral camptothecin analog that has exhibited antitumor activity in breast cancer patients during preclinical studies.
  
  
  METHODS
  Sixteen patients with metastatic breast cancer previously treated with anthracycline and taxane were utilized in the study. Orathecin was administered orally at 1.5 mg/m2 /day for the first five consecutive days of the cycle followed by 2 days of rest on a 7-day schedule. The end points of the study were efficacy and toxicity.
  
  
  RESULTS
  The median age of the patients was 51 years (range, 35-73). Eight patients (50%) had multiple disease sites, and nine patients (56%) received more than three chemotherapy regimens. All patients were evaluated for toxicity, three patients were removed from the study for toxicity or disease progression prior to 8 weeks and were thus not evaluated for efficacy. The median follow-up was 110 days (range, 15-554). There were no responses to treatment. Five of the 13 evaluable patients (38%) had stable disease, eight (61%) had progressive disease. Most adverse events were mild to moderate in intensity. The median time to progression (TTP) for evaluable patients was 109 days (range, 56-374 days) (lower 95% C.I., 57 days). The median survival time was 272 days (lower 95% C.I., 209 days).
  
  
  CONCLUSIONS
  Orathecin at the dose and regimen used in this study resulted in no objective tumor responses for this heavily pretreated population. Accurate risk stratification strategies can improve patients' selection and contribute to determine the appropriate benefit of therapies in MBC.
authors.affiliation: Department of Breast Medical Oncology, M. D. Anderson Cancer Center, The University of Texas, 1515 Holcombe Boulevard, Unit 424, Houston, TX, 77030-4095, USA.
authors.forename: Silwan
authors.initials: S
authors.lastname: Chedid
authors.forename: Edgardo
authors.initials: E
authors.lastname: Rivera
authors.forename: Debbie K
authors.initials: DK
authors.lastname: Frye
authors.forename: Nuhad
authors.initials: N
authors.lastname: Ibrahim
authors.forename: Francisco
authors.initials: F
authors.lastname: Esteva
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Gabriel
authors.initials: G
authors.lastname: Hortobagyi
authors.forename: Karl L
authors.initials: KL
authors.lastname: Mettinger
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C079905:rubitecan; D002166:Camptothecin