Randomized phase II study of perifosine in combination with capecitabine versus capecitabine alone in patients with second- or third-line metastatic colon cancer
| Autor: | C. Bedell, L. T. Campos, Svetislava J. Vukelja, Donald A. Richards, J. P. Letzer, William J. Hyman, Peter Sportelli, L. Gardner, John Nemunaitis, Christopher Hagenstad |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Colorectal cancer business.industry Peri Placebo-controlled study Phases of clinical research Pharmacology medicine.disease Placebo Perifosine Capecitabine chemistry.chemical_compound chemistry Internal medicine medicine business Protein kinase B medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 27:4081-4081 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2009.27.15_suppl.4081 |
| Popis: | 4081 Background: Perifosine (Peri), a synthetic alkylphospholipid, inhibits or modifies a number of different signal transduction pathways (AKT, MAPK and JNK). Peri as a single agent or in combination with other cytotoxic agents, has shown clinical benefit with a manageable safety profile. In a phase I solid tumor trial, Peri was safely combined with capecitabine (Cap) and demonstrated interesting activity in patients (pts) with metastatic colorectal cancer (mCRC), with one patient progression-free for 49 weeks (wks). To assess the true effect of Peri, a phase II was initiated as an exploratory randomized double-blind, placebo controlled study where mCRC pts received Cap in combination with Peri or placebo. Methods: Pts with 2nd or 3rd line mCRC, not previously treated with single agent Cap. ECOG PS 0–1, normal organ/marrow function required. Dose for Cap was 825 mg/m2 BID d 1–14 q 3 weeks. Dose for Peri or placebo was 50 mg qd. Primary outcome analyses included median time to progression (TTP) and response rate (CR+PR). Results: 37 pts have been randomized. Median age 68 (range 32–83) and 57% were male. Median prior Rx was 2 (range 1 - 5). For the analyses, 25 pts were unblinded (12 too early) with 22/25 pts evaluable for response (2 pts off for toxicity at d 14, 46 and 1 patient off at d 4 for other disease; all 3 pts were on Cap + placebo). Results in table below. The log-rank p-value comparing active to placebo for TTP is 0.01. As of 12/08, all unblinded pts are off treatment and 11/12 that were too early remain on treatment with enrollment ongoing. Most frequent (>5%) grade 3 /4 adverse events for Cap + Peri was hand/foot syndrome (16%) and anemia (8%); for Cap + placebo was fatigue (8%). Conclusions: Perifosine in combination with capecitabine was well tolerated, clinically active and more than doubled median TTP over capecitabine alone in pts with advanced, metastatic CRC. [Table: see text] [Table: see text] |
| Databáze: | OpenAIRE |
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