Perifosine Prolongs Survival in Neuroblastoma Patients

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(ChemotherapyAdvisor) – Perifosine shows activity against chemoresistant and radioresistant neuroblastoma, according to a team of researchers from Memorial Sloan-Kettering Cancer Center, New York, NY. This conclusion is based on an abstract entitled “Targeting the PI3K/Akt pathway: Perifosine monotherapy for resistant neuroblastoma (NB) in a phase I/Ib study,” which was presented at the Neuroblastoma Research Conference, which was held in Toronto, Ontario, Canada from June 18 to 21.

Perifosine inhibits Akt, which is aberrantly activated in NB. Phase 1 trials in children and adults with various solid tumors showed modest toxicity with dosages 50–75mg/m2/day using 50mg tablets after a loading dose of 100–200mg/m2 on day 1, noted lead author Brian Kushner, MD, of Memorial Sloan-Kettering Cancer Center. In this Phase 1/2b study, patients with evidence of NB by 123I-metaiodobenzylguanidine (MIBG) received a loading dose of oral perifosine on Day 1 followed by daily maintenance until the primary endpoint of progressive disease (PD) or excessive toxicity was reached.

The investigators reported the following anti-neuroblastoma activity in this study. Complete response (CR) was observed in one patient and a median prolonged progression-free survival of 11 (9±33) months was observed in nine patients, including three with CR in bone marrow by histology. Eight patients had early PD (<1–3 months), while other patients are progression-free with short a follow-up (<4+ months). From Day 1 of perifosine, progression-free survival is 56% (SE+11%) at 12 months. No significant toxicity was observed.

The investigators concluded: “Perifosine shows activity against chemoresistant and radioresistant NB while allowing excellent quality of life and sparing vital organs.”

Abstract (Click on link and find “POC27 on page 188)

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