In vitro studies of the hyperthermic enhancement of activated ifosfamide (4-hydroperoxy-ifosfamide) and glucose isophosphoramide mustard.

Abstract

PURPOSE:

To study the effect of hyperthermia on the cytotoxicity of glucose isophosphoramide mustard (D-19575), a derivative of ifosfamide, which does not require activation and preclinically demonstrates less nephrotoxicity and myelosuppression than ifosfamide.

METHODS:

In vitro studies (using a crystal violet cell survival assay) of the interaction of hyperthermia with D-19575, as well as the activated form of ifosfamide (4-hydroperoxy-ifosfamide, D-18851), were performed using L929 and OVCAR-3 cell lines held at various temperatures (i.e. 37 degrees C (control), 40.5 degrees C, 41.8 degrees C, 42.5 degrees C, and 43 degrees C) for 65 min.

RESULTS:

The following thermal enhancement ratios (TER) were demonstrated: D-19575 in L929 1.2, 2.0 and 2.3 at 40.5, 41.8 and 42.5 degrees C, respectively; for D-18851 in L929 1.7 at 41.8 degrees C; for D-19575 in OVCAR-3 2.1, 3.2 and 3.3 at 40.5, 41.8 and 42.5 degrees C, respectively; for D-18851 in OVCAR-3 4.6 at 41.8 degrees C.

CONCLUSION:

The significant observed increase in cytotoxicity of D-19575 caused by hyperthermia taken together with its known preclinical toxicity profile, encourage its further preclinical and ultimately clinical testing, including its use with whole body and regional hyperthermia.

• Authors: M E Kutz, D L Mulkerin, G J Wiedemann, D M Katschinski, H I Robins
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 40 Issue 2 Pg. 167-71 ( 1997) ISSN: 0344-5704 [Print] Germany
• PMID: 9182839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• beta-D-glucosylisophosphoramide mustard
• Glucose
• Ifosfamide

Topics

• Antineoplastic Agents (pharmacology)
• Cell Survival (drug effects)
• Glucose (analogs & derivatives, pharmacology)
• Humans
• Hyperthermia, Induced
• Ifosfamide (analogs & derivatives, pharmacology)
• Tumor Cells, Cultured