Phase I trial of cyclophosphamide as an immune modulator for optimizing oncolytic reovirus delivery to solid tumors.

ABSTRACT:

Purpose

Reovirus is a wild-type oncolytic virus that is ubiquitous in the environment; most patients are therefore preimmune. Therapeutic administration leads to an increase in neutralizing antireovirus antibody (NARA) titer. We hypothesized that if NARA limited reovirus antitumor activity, the effect might be attenuated by coadministration of cyclophosphamide.

Experimental design

In a phase I study, patients with advanced cancer received cyclophosphamide 3 days before intravenous reovirus serotype 3 Dearing (RT3D). The primary objective was to reduce the resulting rise in NARA titer. Cyclophosphamide dose was escalated from 25-1,000 mg/m(2) through nine cohorts; we aimed to define a well-tolerated immunomodulatory dose.

Results

The combination was well tolerated in 3

SUBMITTER: Roulstone V 

PROVIDER: S-EPMC4821068 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature