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- Title
Preclinical antitumor activity of two novel taxanes.
- Authors
Rose, William C.; Fairchild, Craig; Lee, Francis Y. F.; Rose, W C; Fairchild, C; Lee, F Y
- Abstract
<bold>Purpose: </bold>Two taxane analogs, BMS-184476 and -188797, were evaluated for their in vitro cytotoxicity and in vivo antitumor activity, and compared with paclitaxel and occasionally docetaxel (Taxotere).<bold>Methods: </bold>Cytotoxicity was assessed in vitro using a panel of human tumor cell lines. Several different murine and human tumor models were used in vivo to evaluate the taxane analogs.<bold>Results: </bold>Both compounds were found to have cytotoxic potency similar to paclitaxel and to partially overcome two different forms of paclitaxel resistance. BMS-184476 was found to be clearly superior to paclitaxel in three human xenograft tumor models: A2780 ovarian carcinoma; HCT/pk, a moderately paclitaxel-resistant colon carcinoma; and L2987 lung carcinoma. Additionally, in the clinically derived TAXOL-unresponsive ovarian carcinoma, HOC79, BMS-184476 performed slightly better than paclitaxel and Taxotere. BMS-184476 and paclitaxel were inactive in two murine model systems, M5076 sarcoma and the paclitaxel-resistant M109/txlr lung carcinoma. Against the parental M109 tumor, both BMS-184476 and paclitaxel performed comparably. BMS-184476 was never found to be inferior to paclitaxel. The other taxane analog, BMS-188797, displayed efficacy superior to paclitaxel in four in vivo tumor models: HOC79, HCT/ pk, M109, and L2987 carcinomas. Like paclitaxel and BMS-184476, BMS-188797 was inactive versus M5076 sarcoma.<bold>Conclusions: </bold>Two new taxane analogs were characterized as superior to paclitaxel or Taxotere in several in vivo tumor models. Both BMS-184476 and -188797 are currently in phase I or II clinical trials.
- Subjects
TUMORS; CANCER; ANTINEOPLASTIC agents; CLINICAL trials; PACLITAXEL; CANCER cells; CELL lines
- Publication
Cancer Chemotherapy & Pharmacology, 2001, Vol 47, Issue 2, p97
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/S002800000241