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

• Published in: Journal of clinical oncology Vol. 29; no. 33; pp. 4394 - 4400
• Main Authors: BENDELL, Johanna C, NEMUNAITIS, John, VUKELJA, Sasha J, HAGENSTAD, Christopher, CAMPOS, Luis T, HERMANN, Robert C, SPORTELLI, Peter, GARDNER, Lesa, RICHARDS, Donald A
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.11.2011
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Capecitabine; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Double-Blind Method; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Medical sciences; Middle Aged; Neoplasm Metastasis; Phosphorylcholine - administration & dosage; Phosphorylcholine - analogs & derivatives; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Antineoplastic agent; Human; Rectal disease; Capecitabine; Perifosine; Fluoropyrimidine derivatives; Colorectal cancer; Malignant tumor; Metastasis; Prodrug; Randomized controlled trial; Colonic disease; Cancerology; Phase II trial; Placebo; Digestive diseases; Intestinal disease; Clinical trial; Advanced stage; Second line treatment; Pyrimidine nucleoside; Cancer; Third line treatment
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2011.36.1980

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 (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. 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. 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.