TY - JOUR
T1 - A phase II trial of perifosine, an oral alkylphospholipid, in recurrent or metastatic head and neck cancer
AU - Argiris, Athanassios
AU - Cohen, Ezra
AU - Karrison, Theodore
AU - Esparaz, Benjamin
AU - Mauer, Ann
AU - Ansari, Rafat
AU - Wong, Stuart
AU - Lu, Yi
AU - Pins, Michael
AU - Dancey, Janet
AU - Vokes, Everett
N1 - Funding Information:
24. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000; 92:205-16.
PY - 2006/7
Y1 - 2006/7
N2 - Background: Novel, effective therapies are warranted in the management of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Perifosine is an oral alkylphospholipid that inhibits AKT phosphorylation and has shown preclinical antitumor activity in head and neck cancer cell lines and xenografts. Patients And Methods: We conducted a phase II trial of perifosine in patients with incurable, recurrent or metastatic SCCHN. Previous therapy for recurrent or metastatic disease was limited to no more than one prior chemotherapy and one prior targeted/ biologic agent regimen. Patients had to have measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and adequate laboratory parameters. Perifosine was given as a loading dose of 150 mg every 6 hours x 6 doses orally in the first two days, with antiemetic prophylaxis, followed by 100 mg/day orally without interruption. Administration via gastrostomy tube was allowed. Tumor response was assessed every two cycles (eight weeks). Biomarkers in pathways potentially affected by perifosine, including AKT, P-AKT, P38, p53 and p21 were measured on tumor tissue by immunohistochemistry by manual and automated methods. Results: Nineteen patients were enrolled. No objective responses were observed. One patient had stable disease as best response and 18 patients progressed at first evaluation. The median overall survival time was 5.5 months and the median progression-free survival time was 1.7 months. The most frequent toxicities were gastrointestinal (constipation, nausea, vomiting) and fatigue. One patient developed grade 4 anorexia. Although the sample size was small, a significant correlation was detected between high expression of P38 and AKT in baseline tumor tissue and better survival. Conclusions: Perifosine in the doses and schedule used lacks single-agent activity in SCCHN. Our data do not justify further investigation of perifosine as a single agent in SCCHN.
AB - Background: Novel, effective therapies are warranted in the management of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Perifosine is an oral alkylphospholipid that inhibits AKT phosphorylation and has shown preclinical antitumor activity in head and neck cancer cell lines and xenografts. Patients And Methods: We conducted a phase II trial of perifosine in patients with incurable, recurrent or metastatic SCCHN. Previous therapy for recurrent or metastatic disease was limited to no more than one prior chemotherapy and one prior targeted/ biologic agent regimen. Patients had to have measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and adequate laboratory parameters. Perifosine was given as a loading dose of 150 mg every 6 hours x 6 doses orally in the first two days, with antiemetic prophylaxis, followed by 100 mg/day orally without interruption. Administration via gastrostomy tube was allowed. Tumor response was assessed every two cycles (eight weeks). Biomarkers in pathways potentially affected by perifosine, including AKT, P-AKT, P38, p53 and p21 were measured on tumor tissue by immunohistochemistry by manual and automated methods. Results: Nineteen patients were enrolled. No objective responses were observed. One patient had stable disease as best response and 18 patients progressed at first evaluation. The median overall survival time was 5.5 months and the median progression-free survival time was 1.7 months. The most frequent toxicities were gastrointestinal (constipation, nausea, vomiting) and fatigue. One patient developed grade 4 anorexia. Although the sample size was small, a significant correlation was detected between high expression of P38 and AKT in baseline tumor tissue and better survival. Conclusions: Perifosine in the doses and schedule used lacks single-agent activity in SCCHN. Our data do not justify further investigation of perifosine as a single agent in SCCHN.
KW - AKT
KW - Alkylphospholipids
KW - Head and neck cancer
KW - Perifosine
KW - Recurrent or metastatic
KW - Squamous cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=33751184394&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751184394&partnerID=8YFLogxK
U2 - 10.4161/cbt.5.7.2874
DO - 10.4161/cbt.5.7.2874
M3 - Article
C2 - 16760642
AN - SCOPUS:33751184394
VL - 5
SP - 766
EP - 770
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
SN - 1538-4047
IS - 7
ER -