A phase II trial of perifosine, an oral alkylphospholipid, in recurrent or metastatic head and neck cancer. Cancer Biol Ther 2006 Jul;5(7):766-70
Date
06/09/2006Pubmed ID
16760642DOI
10.4161/cbt.5.7.2874Scopus ID
2-s2.0-33751184394 (requires institutional sign-in at Scopus site) 102 CitationsAbstract
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.
Author List
Argiris A, Cohen E, Karrison T, Esparaz B, Mauer A, Ansari R, Wong S, Lu Y, Pins M, Dancey J, Vokes EAuthor
Stuart J. Wong MD Center Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Administration, OralAdult
Aged
Aged, 80 and over
Antineoplastic Agents
Biomarkers, Tumor
Carcinoma, Squamous Cell
Female
Head and Neck Neoplasms
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
Phospholipids
Phosphorylcholine
Proto-Oncogene Proteins c-akt
p38 Mitogen-Activated Protein Kinases