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Alterations in Polyamine Metabolism during Continuous Intravenous Infusion of -Difluoromethylornithine Showing Correlation of Thrombocytopenia with -Difluoromethylornithine Plasma Levels¹

Departments of Medical Oncology [J. A. A., B. L.] and General Surgery [D. M. O., V. B. G., K. N.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Polyamine biosynthesis is important for cell proliferation and growth. The purpose of this study was to determine the biochemical and pharmacological parameters associated with host toxicity from a continuous infusion of -difluoromethylornithine (DFMO). Twenty-five patients with metastatic carcinoma of the colon or rectum received continuous infusion of DFMO at a median dose of 8 g/m²/day (range, 6–14) for 28 days. DFMO plasma levels, RBC, plasma putrescine, spermidine, and spermine levels, and patient toxicities were evaluated. There was a significant decrease in RBC and plasma levels of putrescine, spermidine, and spermine following DFMO administration compared with the baseline RBC and plasma levels. Pearson correlation coefficient comparing nadir platelet count and steady-state DFMO level was statistically significant (n = 37; P < 0.01; r = -0.53). Sustained suppression of circulating polyamine levels was also achieved with continuous DFMO infusion. The correlation between steady-state plasma DFMO levels and lowering of platelet count warrants prospective evaluation to determine its clinical usefulness.

¹ This work was supported by Grant R01 CA34465 from the National Cancer Institute, Bethesda, MD, and by a grant from Baxter-Travenol Corp., Deerfield, IL.

² To whom requests for reprints should be addressed, at Department of Medical Oncology, M. D. Anderson Cancer Center, 1515 Holcombe Ave., Box 78, Houston, TX 77030.

Received 12/ 1/88. Revised 4/19/89. Accepted 7/13/89.