Aeterna Zentaris: Phase 1 Results Show Perifosine's Activity Against Neuroblastoma

Aeterna Zentaris Inc. AEZS today announced that Phase 1 trial results for its oral PI3K/Akt inhibitor, perifosine, showed the drug's activity against chemo-resistant and radio-resistant neuroblastoma, while allowing good quality of life and sparing vital organs. Neuroblastoma is a type of childhood cancer which usually begins in nerve tissues. Data were presented yesterday by Brian H. Kushner, MD, of the Memorial Sloan-Kettering Cancer Center in New York, during a poster session at the Advances in Neuroblastoma Research Conference which is being held in Toronto, Canada. The Study This was an open-label dose-escalating Phase 1 trial to assess toxicity and efficacy of perifosine, given in monotherapy to patients with neuroblastoma (clinicaltrials.gov NCT00776867). Patients were dosed using 50mg tablets and received a loading dose (100-200mg/m2) of perifosine on day 1, followed by daily maintenance doses (50-75mg/m2) until progressive disease or dose-limiting toxicity. Disease evaluation was every 8 weeks. The poster reported on the outcome of 24 patients treated to date; patients had a median age of 8.7 years (range 4.7 to 33.5) and a median disease duration of 4.6 years (range 2.5 to 8.0). Three patients were treated for neuroblastoma refractory to primary therapy, and 21 for neuroblastoma resistant to salvage therapy after 1 to 5 (median 2) prior relapses. Prior therapy included high-dose conventional induction and 2nd line chemotherapy (all patients); myeloablative chemotherapy and stem cell transplantation (10 patients) and/or targeted radiotherapy with I-131-MIBG (9 patients). Results Anti-neuroblastoma activity was evident by a 50% progression-free survival rate at 12 months (Standard Error 11%) and included 1 complete remission (CR) based on a normalized MIBG scan and 3 patients with improved MIBG scan and normalized bone marrow histology over prolonged follow-up (up to 37+months). No significant toxicity was seen, in particular no grade 3 problems, and no safety issues were encountered in 6 patients who started treatment with pre-existing thrombocytopenia and/or grade 3 elevations in liver enzymes. Conclusions Perifosine was well tolerated, without major toxicity - hence, compatible with good quality of life; Perifosine monotherapy may help in progression-free survival of patients with persistent/stable MIBG-positivity in skeletal sites; Perifosine may have a possible role with chemotherapy, radiation therapy, and/or other agents active in PI3K/Akt pathway.