title: Randomized placebo-controlled phase II trial of perifosine plus capecitabine as second- or third-line therapy in patients with metastatic colorectal cancer.
abstract: OBJECTIVE
  In a multicenter, double-blind phase II trial, we compared the efficacy and safety of perifosine plus capecitabine (P-CAP) with placebo plus capecitabine (CAP) in patients with metastatic colorectal cancer (mCRC) who had progressed after as many as two prior therapies.
  
  
  METHODS
  Patients (n = 38) not previously treated with capecitabine received P-CAP (perifosine 50 mg orally once daily, days 1 to 21 and CAP 825 mg/m(2) orally twice daily, days 1 to 14) or CAP (825 mg/m(2) orally twice daily, days 1 to 14) in 21-day cycles until disease progression. The primary end point was time to progression (TTP). Secondary end points included overall survival (OS), overall response rate (ORR), safety, and tolerability.
  
  
  RESULTS
  Twenty patients were randomly assigned to P-CAP and 18 to CAP. Median TTP (27.5 v 10.1 weeks; P < .001) and median OS (17.7 v 7.6 months; P = .0052) were improved in patients receiving P-CAP versus CAP. ORR was 20% v 7% in the P-CAP and CAP groups, respectively, and one patient in the P-CAP group had a complete response. A subset analysis of fluorouracil-refractory patients showed a median TTP of 17.6 v 9.0 weeks (P < .001) and median OS of 15.1 v 6.5 months (P = .0061). Toxicities, including diarrhea, nausea, fatigue, and hand-foot syndrome, were manageable.
  
  
  CONCLUSIONS
  P-CAP showed promising clinical activity compared with CAP in previously treated patients with mCRC. A phase III trial is underway comparing P-CAP with CAP in patients with refractory mCRC.
authors.affiliation: Sarah Cannon Research Institute, 250 25th Ave North, Suite 100, Nashville, TN 37203, USA. jbendell@tnonc.com
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Bendell
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: Sasha J
authors.initials: SJ
authors.lastname: Vukelja
authors.forename: Christopher
authors.initials: C
authors.lastname: Hagenstad
authors.forename: Luis T
authors.initials: LT
authors.lastname: Campos
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hermann
authors.forename: Peter
authors.initials: P
authors.lastname: Sportelli
authors.forename: Lesa
authors.initials: L
authors.lastname: Gardner
authors.forename: Donald A
authors.initials: DA
authors.lastname: Richards
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004311:Double-Blind Method; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D003841:Deoxycytidine; D010767:Phosphorylcholine; C105905:perifosine; D000069287:Capecitabine; D005472:Fluorouracil