Immunostimulating and cancer-reductive experimental therapy with the oxazaphosphorine cytostatic SUM-IAP

SUM-IAP is an aldo-ifosfamide-perhydrothiazine derivative that, under physiological conditions, spontaneously hydrolyzes to SUM-aldo-ifosfamide. In SUM-IAP, one 2-chloroethyl group of the alkylating function of aldo-ifosfamide-perhydrothiazine is substituted by a mesyl-ethyl group. The compound was synthesized to investigate the influence of the alkylating function of aldo-ifosfamide on the antitumor activity of oxazaphosphorine cytostatics. In chemotherapy experiments in CD2F1 mice with advanced subcutaneously growing P388 mice leukemia cells, the primary tumor was reduced below the detection level with two highly dosed injections on days 7 and 8, but after 14 days, the primary tumor was measurable again. The primary tumor and detectable metastases killed the animals 29–30 days after SUM-IAP application. When, however, the animals were treated again with two highly dosed injections on day 14 and 15, a 4–5 times increase in the number of leukocytes was measured and all animals survived the observation period of 100 days. In the high, cancer-reductive dose range, SUM-IAP is not only a cytotoxic but also an immunostimulating oxazaphosphorine cytostatic. Correspondence to Georg Voelcker, PhD, Institute of Biochemistry II, Goethe University Frankfurt Medical School, Frankfurt, Germany Tel: +49 69 63015652; fax: +49 69 63015577; e-mails: voelcker@biochem2.de, voelckerdr@aol.com Received October 18, 2017 Accepted January 25, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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