Summary
Vinzolidine (VZL), a semisynthetic vinblastine (VLB) derivative, was tested against a variety of solid tumors in the human tumor clonogenic assay (HTCA). The emphasis was on continuous drug exposure because of the schedule-dependency of the vincas and long half-life of VZL. Of tumor types with more than ten samples tested, the percentage of cases exhibiting inhibition (50% or less of control) of tumor colony forming units (TCFU) was as follows: melanoma (48%), lung cancer (48%), breast cancer (40%), renal cancer (33%), and ovarian cancer (24%). In tumor types tested less frequently, inhibition of TCFU after continuous or one hour drug exposure was observed in 2/7 colon cancers, 1/3 pancreatic cancers and 3/4 gastric cancers. Paired analysis of tumors tested to both VZL and VLB demonstrated no significant difference in overall activity of these two vinca alkaloids.
VZL appears to be a promising drug for clinical trials, with in vitro activity in melanoma, lung and breast cancers. More interesting is the suggestion of activity in gastrointestinal tumors, especially colon cancer which is generally resistant to drugs in the HTCA and in vivo.
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References
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Takasugi, B.J., Salmon, S.E., Nelson, R.L. et al. Antitumor activity of vinzolidine in the human tumor clonogenic assay and comparison with vinblastine. Invest New Drugs 2, 49–53 (1984). https://doi.org/10.1007/BF00173786
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DOI: https://doi.org/10.1007/BF00173786