PEPI: Protracted Etoposide in a Phase II Upfront Window for Induction Therapy for High Risk Neuroblastoma
Neuroblastoma is the most common extracranial solid tumor of childhood. Approximately half
of the children newly diagnosed with this tumor will have metastatic disease or
histologically aggressive large tumors that are at "high risk" for treatment failure.
Therapy for high risk neuroblastoma consists of intensive chemotherapy, surgery, radiation
therapy, high dose therapy with autologous hematopoietic stem cell rescue (HDT/SCR), and
biologic agents such as retinoids. Dose intensification has long been the focus of clinical
research with development of maximum intensity induction regimens and multiple cycles of
HDT/SCR. The majority of tumors will respond initially to this combination therapy, but
relapse is common with a three-year event free survival of 30 to 40%. Additionally, the risk
of acute and chronic toxicities from therapy is high and increases with intensification.
Review of risk factors for relapse or progressive disease suggests that response of tumors
to induction chemotherapy is a predictor of poor outcomes with current treatment strategies.
Novel approaches to induction therapy may be beneficial to the overall survival of children
with HRNB; because the response rate to induction has historically been good, care must be
taken when modifying the standard regimens. The trial that follows aims to address the
initial tumor response by changing the dosing of etoposide, a known effective agent in both
newly- diagnosed and salvage therapy, from bolus to protracted dosing. This dosing schedule
may provide an anti- angiogenic effect as well as a cytotoxic anti-tumor effect. If this
regimen proves equally effective as prior regimens it could serve as a backbone for the
incorporation of other novel targeted agents. Additional research to improve understanding
of neuroblastoma, the patients, and the impacts of therapy are also included for design of
future clinical trials.
This study will evaluate the efficacy of protracted etoposide in combination with standard
Cisplatin dosing. Although the most common schedule for children has historically been 50
mg/m2/day for 21 days, in this study the dose will be reduced to 14 days. A 14 day schedule
will allow other chemotherapy to be given on a 21 day schedule while keeping the total
cumulative dose of etoposide within the range of other prior effective regimens.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Response Rate Associated With Two Cycles of Cisplatin With Protracted Oral Etoposide When Administered as Up-front Window Therapy to Previously Untreated Children With High Risk Neuroblastoma Tumors.
Peter Zage, MD
Baylor College of Medicine
United States: Institutional Review Board
|Texas Children's Hospital||Houston, Texas|