title: Temsirolimus Maintenance Therapy After Docetaxel Induction in Castration-Resistant Prostate Cancer.
abstract: CONCLUSIONS
  Temsirolimus maintenance therapy after docetaxel induction chemotherapyis safe in patients with castration-resistant prostate cancer, although biochemical or tumor responses are rare;does not diminish quality of life; anddelays radiological and/or symptomatic progression by approximately 6 months.
  
  
  BACKGROUND
  No standard therapy is available for men with castration-resistant prostate cancer (CRPC) who have responded to docetaxel and do not yet have disease progression. Hence, we designed a single-arm phase II trial to explore whether the mTOR inhibitor temsirolimus can maintain the response to docetaxel without compromising quality of life.
  
  
  METHODS
  After successful docetaxel induction (75 mg/m(2) every 3 weeks; 6-10 cycles), 21 CRPC patients underwent temsirolimus maintenance treatment (25 mg weekly; 4 weeks per cycle). The primary endpoint was the time to treatment failure (TTTF) (i.e., radiological and/or symptomatic progression). The secondary endpoints included the tumor response rate (RECIST 1.0), safety (National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0), quality of life (Functional Assessment of Cancer Therapy-Prostate [FACT-P]), pain (Present Pain Intensity [PPI] scale), prostate-specific antigen (PSA) parameters, including time to PSA progression (TTPP) according to Prostate Cancer Clinical Trials Working Group criteria, and serial enumeration of circulating endothelial cells (CECs) and endothelial progenitor cells (CEPs).
  
  
  RESULTS
  Patients received a median of 7 cycles of temsirolimus (range, 1-28), resulting in a median TTTF of 24.3 weeks (95% confidence interval [CI], 16.1-33.0), 1 partial tumor response (4.8%), 1 PSA response (4.8%), and a median TTPP of 12.2 weeks (95% CI, 7.8-23.9). Grade 3-4 adverse events were infrequent, and FACT-P and PPI scores remained stable during treatment. CECs did not predict clinical benefit, and CEPs were not consistently detectable.
  
  
  CONCLUSIONS
  Temsirolimus maintenance therapy after successful docetaxel induction is feasible, does not adversely affect quality of life, and, in this exploratory single-arm phase II study, resulted in a median TTTF of 24.3 weeks.
authors.affiliation: Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada urban.emmenegger@sunnybrook.ca.
authors.forename: Urban
authors.initials: U
authors.lastname: Emmenegger
authors.affiliation: Queen's University Cancer Research Institute, Kingston, Ontario, Canada.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Booth
authors.affiliation: Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Berry
authors.affiliation: Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Srikala S
authors.initials: SS
authors.lastname: Sridhar
authors.affiliation: London Health Sciences Centre, London, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.affiliation: Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nesan
authors.initials: N
authors.lastname: Bandali
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Chow
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: Lee
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shan
authors.initials: S
authors.lastname: Man
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kerbel
authors.affiliation: Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yoo-Joung
authors.initials: YJ
authors.lastname: Ko
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; C401859:temsirolimus; D020123:Sirolimus