Phase I/II Study of Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer
Vorinostat inhibits growth and induces apoptosis in various human carcinoma cells.
Furthermore, it affects the expression of various genes that are necessary for proliferation
of cancer cells. Vorinostat also appears to block angiogenic signaling. Pre-treating four
human cancer cell lines (including a brain tumor line) with vorinostat increased the killing
efficiency of etoposide, ellipticine, doxorubicin, or cisplatin, but not of the
topoisomerase I inhibitor camptothecin 13. Topoisomerase II is a ubiquitous nuclear enzyme
that is involved in DNA replication, transcription, chromosome segregation, and apoptosis.
It is the target for several anti-cancer drugs including etoposide. Treatment with HDAC
inhibitors induces expression of topoisomerase II in cancer cells and enhances the
sensitivity to etoposide 14.
Early phase clinical trials have demonstrated single agent anti-cancer activity with
vorinostat. In our study, combination of vorinostat with carboplatin and paclitaxel,
demonstrated promising anticancer activity against NSCLC, including histological subsets of
patients whose tumors demonstrated neuroendocrine differentiation 8. For all these reasons,
vorinostat is a rational choice to combine with the regimen of carboplatin and etoposide for
evaluation in patients with SCLC-ED.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Assess maximum tolerated dose of vorinostat combined with carboplatin + etoposide for patients with extensive disease SCLC.
An expected average of 2 years
Chandra P Belani, MD
Penn State College of Medicine
United States: Institutional Review Board
|Penn State College of Medicine, Penn State Milton S. Hershey Medical Center||Hershey, Pennsylvania 17033|