A phase II trial of perifosine, an oral alkylphospholipid, in recurrent or metastatic head and neck cancer

摘要: Background Novel, effective therapies are warranted in the management of recurrent or metastatic squamous cell carcinoma head and neck (SCCHN). Perifosine is an oral alkylphospholipid that inhibits AKT phosphorylation has shown preclinical antitumor activity cancer lines xenografts. Patients methods We conducted a phase II trial perifosine patients with incurable, SCCHN. Previous therapy for disease was limited to no more than one prior chemotherapy targeted/biologic agent regimen. had have measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate laboratory parameters. given as loading dose 150 mg every 6 hours x doses orally first two days, antiemetic prophylaxis, followed by 100 mg/day without interruption. Administration via gastrostomy tube allowed. Tumor response assessed cycles (eight weeks). Biomarkers pathways potentially affected perifosine, including AKT, P-AKT, P38, p53 p21 were measured on tumor tissue immunohistochemistry manual automated methods. Results Nineteen enrolled. No objective responses observed. One patient stable best 18 progressed at evaluation. The median overall survival time 5.5 months progression-free 1.7 months. most frequent toxicities gastrointestinal (constipation, nausea, vomiting) fatigue. developed grade 4 anorexia. Although sample size small, significant correlation detected between high expression P38 baseline better survival. Conclusions schedule used lacks single-agent Our data do not justify further investigation single