title: Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer.
abstract: OBJECTIVE
  In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated.
  
  
  METHODS
  Patients (n = 109) were randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, adverse events, and pharmacokinetics of temsirolimus.
  
  
  RESULTS
  Temsirolimus produced an objective response rate of 9.2% (10 partial responses) in the intent-to-treat population. Median time to tumor progression was 12.0 weeks. Efficacy was similar for both dose levels but toxicity was more common with the higher dose level, especially grade 3 or 4 depression (10% of patients at the 250-mg dose level, 0% at the 75-mg dose level). The most common temsirolimus-related adverse events of all grades were mucositis (70%), maculopapular rash (51%), and nausea (43%). The most common, clinically important grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%).
  
  
  CONCLUSIONS
  In heavily pretreated patients with locally advanced or metastatic breast cancer, 75 and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a generally tolerable safety profile.
authors.affiliation: Department of Clinical Oncology, Nottingham City Hospital, Hucknall Rd, Nottingham N65 1PB, United Kingdom. schan2@ncht.trent.nhs.uk
authors.forename: Stephen
authors.initials: S
authors.lastname: Chan
authors.forename: Max E
authors.initials: ME
authors.lastname: Scheulen
authors.forename: Stephen
authors.initials: S
authors.lastname: Johnston
authors.forename: Klaus
authors.initials: K
authors.lastname: Mross
authors.forename: Fatima
authors.initials: F
authors.lastname: Cardoso
authors.forename: Christian
authors.initials: C
authors.lastname: Dittrich
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eiermann
authors.forename: Dagmar
authors.initials: D
authors.lastname: Hess
authors.forename: Rudolph
authors.initials: R
authors.lastname: Morant
authors.forename: Vladimir
authors.initials: V
authors.lastname: Semiglazov
authors.forename: Markus
authors.initials: M
authors.lastname: Borner
authors.forename: Marc
authors.initials: M
authors.lastname: Salzberg
authors.forename: Valerijus
authors.initials: V
authors.lastname: Ostapenko
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Illiger
authors.forename: Dirk
authors.initials: D
authors.lastname: Behringer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bardy-Bouxin
authors.forename: Joseph
authors.initials: J
authors.lastname: Boni
authors.forename: Steven
authors.initials: S
authors.lastname: Kong
authors.forename: Maria
authors.initials: M
authors.lastname: Cincotta
authors.forename: Laurence
authors.initials: L
authors.lastname: Moore
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019540:Area Under Curve; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011494:Protein Kinases / Q000187:drug effects*; D012449:Safety; D016879:Salvage Therapy; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012983:Soft Tissue Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D058570:TOR Serine-Threonine Kinases; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus