Abstract:
:Taxotere (RP 56976, NSC 628503) is a new semisynthetic analog of taxol (NSC 125973) with promising antitumor activity in a variety of preclinical screening systems. Clinical responses after treatment with taxol have been observed in ovarian cancer, breast, lung cancer and melanoma. Both agents act through induction of microtubule polymerization. We have studied and compared the antiproliferative action of Taxotere and taxol against a variety of freshly explanted human tumor specimens using an in vitro soft agar cloning system. Final concentrations of 0.025-10 micrograms/ml were used for both agents in short-term (1 h) or continuous (14 days) incubations. Taxotere was studied using a 1 h incubation in a total of 167 tumor specimens of which 85 (51%) were evaluable. At 10 micrograms/ml, Taxotere inhibited 32 out of 78 (41%) specimens (colony formation less than or equal to 0.5 x control). Cytotoxicity of Taxotere was observed against breast, lung, ovarian, colorectal cancer and melanoma tumor colony forming units. For comparison, 227 specimens were exposed to taxol for 1 h. At 10 micrograms/ml, 32 out of 97 evaluable specimens (33%) were significantly inhibited. Cytotoxicity was observed against breast, lung, ovarian, colorectal cancer and melanoma tumor colony forming units. In head-to-head comparisons, 29 specimens were found more sensitive to Taxotere than taxol, while only 13 were more sensitive to taxol than to Taxotere. These data indicate that cross-resistance between the two agents is incomplete and that on a concentration basis Taxotere is more cytotoxic than taxol in the majority of human primary tumor specimens evaluated.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Hanauske AR,Degen D,Hilsenbeck SG,Bissery MC,Von Hoff DDdoi
10.1097/00001813-199204000-00008subject
Has Abstractpub_date
1992-04-01 00:00:00pages
121-4issue
2eissn
0959-4973issn
1473-5741journal_volume
3pub_type
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journal_title:Anti-cancer drugs
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