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In Vitro Activity of Bleomycin, Tallysomycin S10b, and Liblomycin against Fresh Human Tumor Cells¹

Departments of Hematology [E. A. T., G. S.], Experimental Radiotherapy [F. L. B.], Medical Oncology [J. A. A., R. A. N.], and Cell Biology [D. F.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

The objective of this study was to compare the relative in vitro cytotoxicity of bleomycin to that of two newer-generation analogues, tallysomycin S10b and liblomycin. The latter compound is of particular interest as it has recently been shown in preclinical studies to be free of a potential to cause pulmonary injury and yet to possess only a minor potential to produce myelotoxicity. Using the adhesive tumor cell culture system, we evaluated the activity of these three drugs against a panel of 13 human tumors of various types. The range of concentrations chosen was determined and normalized using a nonleukemic permanent mouse hematopoietic progenitor cell line.

Those drug concentrations achieving 90% inhibition of growth (IC₉₀) against the murine cell line were: 6.11 µM bleomycin; 7.53 µM tallysomycin S10b; and 0.6 µM liblomycin. When tested against fresh human tumors at equally myelotoxic IC₉₀ concentrations, bleomycin and tallysomycin S10b (nonmyelotoxic compounds) both achieved 90% growth inhibition of all tumors, while liblomycin (a myelotoxic compound) produced an IC₉₀ inhibition in 69% of all tumors. A comparison of drug IC₉₀ values against individual fresh tumors indicated a correlation between bleomycin and its structurally related analogue tallysomycin S10b. No such correlation, however, was seen with liblomycin in comparison to either bleomycin or tallysomycin S10b. The relative activity of liblomycin versus that of bleomycin and tallysomycin S10b varied with individual tumors tested. The response rate of liblomycin, a myelotoxic compound within this normalized range, appears promising. These data represent the first comparison of liblomycin to bleomycin against a spectrum of fresh human tumors using a stem cell assay technique.

¹ Supported by Grant JMV:bg 11783 from LifeTrac, Ltd., Irvine, CA, by a National Cancer Institute Grant CA47847 to R. A. N. and RR511-23 to D. F.

² Recipient of a fellowship from L'Oeuvre Belge du Cancer and participant in the Visitor Exchange Program of the Fulbright-Hays Foundation. Permanent affiliation: Department of Internal Medicine, Institut Jules Bordet, 1 rue Héger-Bordet, 1000 Brussels, Belgium.

³ To whom requests for reprints should be addressed, at Section of Pharmacology, Box 52, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.

Received 7/ 1/88. Revised 11/ 3/88. Accepted 11/14/88.