title: The mTOR inhibitor everolimus in combination with carboplatin in metastatic breast cancer--a phase I trial.
abstract: OBJECTIVE
  Despite advances in the the first- and second-line treatment of metastatic breast cancer, there remains a large unmet need for additional treatment options. As preclinical studies have suggested that combining everolimus with carboplatin may produce higher activity than each drug by itself, we initiated a phase I study of this combination.
  
  
  METHODS
  Patients with pre-treated metastatic breast cancer received weekly carboplatin at AUC2 and daily oral everolimus at different dose-levels (level I: 2.5 mg; II: 5 mg; III: 7.5 mg; IV: 10 mg). Three patients were assigned to dose-levels I to III, and six to dose-level IV. The primary end-point was to determine the maximum tolerated dose (MTD).
  
  
  RESULTS
  Fifteen patients were recruited to the study. The median number of previous chemotherapies was four (range: 1-11). No dose-limiting toxicity occurred at levels I-III during the first cycle. Based on the pre-determined definition, the maximum planned dose-level IV was selected as the MTD. Patients received a median of four cycles of treatment (range 1-13). Most frequent grade 3 and 4 toxicities included leukopenia, thrombocytopenia and infection. Response rates were as follows: 21% partial response, 43% stable disease, and 36% progressive disease.
  
  
  CONCLUSIONS
  Carboplatin and everolimus is a well-tolerated combination for heavily pre-treated metastatic breast cancer. Everolimus (10 mg/d) and carboplatin (AUC2 weekly) were defined as the MTD. This dose is currently being employed in an ongoing phase II trial.
authors: Department of Oncology and Hematology, Charité - Universitätsmedizin Berlin, Charitéplatz 1,10117 Berlin, Germany.
authors: Sandra
authors: S
authors: Schwarzlose-Schwarck
authors: Christian W
authors: CW
authors: Scholz
authors: Anne C
authors: AC
authors: Regierer
authors: Peter
authors: P
authors: Martus
authors: Christian
authors: C
authors: Neumann
authors: Piet
authors: P
authors: Habbel
authors: Hongyu
authors: H
authors: Liu
authors: Chuanbing
authors: C
authors: Zang
authors: Jan-Hendrik
authors: JH
authors: Schefe
authors: Carsten-Oliver
authors: CO
authors: Schulz
authors: Kurt
authors: K
authors: Possinger
authors: Jan
authors: J
authors: Eucker
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage; D000068338:Everolimus; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000068338:Everolimus; D016190:Carboplatin; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus