Treatment of relapsed XXXX with an adenoviral vector containing the herpes simplex @entity1014 kinase gene followed by @entity4540 .

@entity1 @entity5 @entity11 @entity1014 @entity4540
Between November 1998 and December 2001, we treated 14 @entity1 with advanced recurrent high-grade @entity11 with a total dose of 4.6 x 10(8), 4.6 x 10(9), 4.6 x 10(10), or 4.6 x 10(11) viral particles (VP) of a replication-incompetent adenoviral vector harboring the herpes simplex virus @entity1014 kinase gene driven by the adenoviral major late promoter (IG.Ad.MLPI.TK), followed by @entity4540 (GCV) treatment. The VP-to-infectious-unit ratio was 40. The vector was administered by 50 intraoperative wound-bed injections of 0.2 ml each (total volume 10 ml). The study's primary objective was to determine the safety of this treatment and establish the maximum tolerated dose (MTD). Injection of all doses of IG.Ad.MLPI.TK followed by GCV was safely tolerated and MTD was not reached. All @entity1 had recurrence or progression of the @entity5 1-24 months (median 3.5 months) after gene therapy. The overall median survival was 4 months. Four @entity1 survived longer than 1 year following gene therapy. One @entity1 is still alive, with histologically confirmed progression of the @entity5 , 29 months after treatment. Ten @entity1 died within 8 months of treatment, all from progression of the @entity5 . In 5 @entity1 residual and measurable @entity5 was visible on the direct (<48 h) postoperative MRI. No objective radiological response was documented on subsequent MRI. None of the @entity1 came to autopsy. In conclusion, the administration of 4.6 x 10(11) VP of IG.Ad.MLPI.TK by 50 injections into the wound bed following resection of recurrent @entity11 , followed by GCV treatment, was well tolerated.
