PERIFOSINE IN COLORECTAL CANCER

J Clin Oncol. 2011 Oct 3. [Epub ahead of print]

Randomized Placebo-Controlled Phase II Trial of Perifosine Plus Capecitabine As
Second- or Third-Line Therapy in Patients With Metastatic Colorectal Cancer.

Bendell JC, Nemunaitis J, Vukelja SJ, Hagenstad C, Campos LT, Hermann RC,
Sportelli P, Gardner L, Richards DA.

Johanna C. Bendell, Sarah Cannon Research Institute, Nashville, TN; John
Nemunaitis, Mary Crowley Cancer Research Center, Dallas; Sasha J. Vukelja and
Donald A. Richards, Texas Oncology, Tyler; Luis T. Campos, Oncology Consultants, 
Houston, TX; Christopher Hagenstad, Suburban Hematology/Oncology, Lawrenceville; 
Robert C. Hermann, Northwest Georgia Oncology Center, Marietta, GA; and Peter
Sportelli and Lesa Gardner, Keryx Biopharmaceuticals, New York, NY.

PURPOSEIn 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 METHODSPatients (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.ResultsTwenty 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. CONCLUSIONP-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.