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Increased antitumour activity of mesyl-I-aldophosphamide-perhydrothiazine, in vivo but not in vitro, compared to I-aldophosphamide-perhydrothiazine

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Abstract

When equitoxic dosages of ifosfamide and I-aldophosphamide-perhydrothiazine (IAP) were tested for antitumour activity in the P388 mouse leukaemia model, 80% long-term survival (for more than 100 days) was achieved with IAP whereas, in the ifosfamide group, all mice died from tumour growth within 60 days. Even better antitumour activity, compared with ifosfamide, was observed with an IAP derivative (SUM-IAP) in which one 2-chloroethyl group of the alkylating function is substituted by a mesylethyl group. Evaluation of tumour growth curves following treatment with IAP and SUM-IAP revealed the antitumour activity of SUM-IAP to be 104–105 times higher than that of IAP. In contrast to the results of these in vivo experiments, IAP was more cytotoxic against P388 mouse leukaemia cells in vitro than was SUM-IAP. The inverse correlation of in vivo antitumour activity and in vitro cytotoxicity indicates that the factors leading to the increase of antitumour activity following chemical modification of IAP differ from those involved in cytotoxicity on the cellular level.

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Received: 9 April 1999 / Accepted: 24 September 1999

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Voelcker, G., Pfeiffer, B., Schnee, A. et al. Increased antitumour activity of mesyl-I-aldophosphamide-perhydrothiazine, in vivo but not in vitro, compared to I-aldophosphamide-perhydrothiazine. J Cancer Res Clin Oncol 126, 74–78 (2000). https://doi.org/10.1007/s004320050012

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  • DOI: https://doi.org/10.1007/s004320050012

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