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Randomized placebo-controlled phase II trial of perifosine plus capecitabine as second- or third-line therapy in patients with metastatic colorectal cancer.

AbstractPURPOSE:
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.
PATIENTS AND 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.
CONCLUSION:
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.
AuthorsJohanna C Bendell, John Nemunaitis, Sasha J Vukelja, Christopher Hagenstad, Luis T Campos, Robert C Hermann, Peter Sportelli, Lesa Gardner, Donald A Richards
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 33 Pg. 4394-400 (Nov 20 2011) ISSN: 1527-7755 [Electronic] United States
PMID21969495 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Deoxycytidine
  • Phosphorylcholine
  • perifosine
  • Capecitabine
  • Fluorouracil
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
  • Capecitabine
  • Colorectal Neoplasms (drug therapy, mortality, pathology)
  • Deoxycytidine (administration & dosage, analogs & derivatives)
  • Double-Blind Method
  • Fluorouracil (administration & dosage, analogs & derivatives)
  • Humans
  • Middle Aged
  • Neoplasm Metastasis
  • Phosphorylcholine (administration & dosage, analogs & derivatives)

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