Phase I study of perifosine monotherapy in patients with recurrent or refractory neuroblastoma

Pediatric Blood & Cancer
Kimikazu MatsumotoHideo Mugishima

Abstract

Perifosine is an alkylphospholipid analog that inhibits or modulates signaling through signal transduction pathways such as Akt, which is enhanced in neuroblastoma (NB) by activation of tyrosine kinase receptors. We conducted a phase I study of perifosine in Japanese patients with recurrent or refractory NB. All patients enrolled were over 2 years of age; all had refractory or relapsed NB and a performance status of greater than 50%. Perifosine was orally administered at a loading dose (100-300 mg) on day 1 and at a maintenance dose (50-150 mg) from day 2 onward. Dose-limiting toxicity (DLT) and pharmacokinetics were assessed in Step 1 and safety and efficacy in Step 2. Nineteen patients were recruited. No DLT was observed. Adverse reactions occurring in more than 30% of the patients were vomiting (63%), nausea (53%), and diarrhea (37%). The mean plasma concentration of perifosine was 27.5 ± 9.8 μM on day 15 and 27.3 ± 11.5 μM on day 29. The response rate (RR) in 18 patients evaluable according to modified International Neuroblastoma Response Criteria was 0%; the disease control rate (DCR) was 56%. Median progression-free survival (PFS) was 122 days. In 11 patients evaluable according to the Response Evaluation Criteria in Soli...Continue Reading

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Citations

Jul 17, 2019·EMBO Molecular Medicine·Sofie MohlinDaniel Bexell
Mar 3, 2020·Mutation Research·M IidaM Toulany
Apr 8, 2020·ACS Pharmacology & Translational Science·Marion Le GrandMaria Kavallaris

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