Phase II study of single agent perifosine in patients with hepatocellular carcinoma (HCC)
| Autor: | Peter Sportelli, John Nemunaitis, R. Niecestro, L. T. Campos, D. Richards, Minal A. Barve, L. Gardner, Joe Stephenson |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Sorafenib
Oncology Cancer Research medicine.medical_specialty business.industry Peri Phases of clinical research Perifosine medicine.disease law.invention Surgery chemistry.chemical_compound Randomized controlled trial chemistry law Hepatocellular carcinoma Internal medicine medicine In patient business Protein kinase B medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 27:e15505-e15505 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2009.27.15_suppl.e15505 |
| Popis: | e15505 Background: Perifosine (Peri) is a novel oral alkylphospholipid with effects on multiple signal transduction pathways including Akt, MAPK and JNK. Unresectable HCC continues to have dismal prognosis. In a phase III randomized study, sorafenib demonstrated a 2% partial response (PR) rate with a median time to symptomatic progression of 4.1 months (mos) and radiologic progression of 5.5 mos, however patients (pts) had not received prior systemic treatment. Hence, additional therapies are needed. Peri was evaluated in a phase II multi-disease trial where 558 pts were randomized to daily vs. weekly schedules of Peri (50/100 mg daily or 900/1,200 mg weekly) with 42 of the pts having HCC. The following are the efficacy and safety results of this sub-group. Methods: Pts with advanced measurable HCC, up to 3 prior systemic treatments allowed. Normal organ / marrow function required. Primary outcome analyses included median time to progression (TTP) and disease control rate (DCR; CR+PR+SD > 12 weeks). Results: Of the 42 HCC pts treated, the median age was 71 (range 26–83), 22 were male and 48% had received > 1 prior systemic therapy. Child-Pugh status not available. As of 12/08, 32/42 pts were evaluable for efficacy (5 withdrew consent < 30 days, 4 toxicity < 30 days, 1 lost to follow up). One patient achieved a PR (3%) and 15 (47%) had stable disease > 12 weeks; overall DCR of 50%. Median TTP was 14 wks (range 2–86). As of 12/08, one patient remains active at 12 mos. The daily dose was well tolerated. The weekly dose was significantly more toxic (3 of the 4 who came off treatment < 30 days due to toxicity were on weekly). Most common grade 1/2 toxicities were GI related and fatigue. Grade 3/4 drug-related toxicities > 10% included: abdominal pain (12%), elevated liver enzymes (10%) and fatigue (10%). Conclusions: Perifosine was well tolerated at the daily dose and overall demonstrates clinical benefit in patients with advanced HCC as reflected by an encouraging TTP. A combination study with sorafenib is ongoing and future randomized studies are under consideration. [Table: see text] |
| Databáze: | OpenAIRE |
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