Experimental antitumor activity of taxotere (RP 56976, NSC 628503), a taxol analogue

• Published in: Cancer research (Baltimore) Vol. 51; no. 18; pp. 4845 - 4852
• Main Authors: BISSERY, M.-C, GUENARD, D, GUERITTE-VOEGELEIN, F, LAVELLE, F
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.09.1991
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Alkaloids - pharmacology; Alkaloids - toxicity; Animals; Antineoplastic agents; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - toxicity; Biological and medical sciences; Carcinoma, Intraductal, Noninfiltrating - drug therapy; Carcinoma, Intraductal, Noninfiltrating - pathology; Chemotherapy; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Female; Leukemia, Experimental - drug therapy; Leukemia, Experimental - pathology; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Mammary Neoplasms, Experimental - drug therapy; Mammary Neoplasms, Experimental - pathology; Medical sciences; Melanoma, Experimental - drug therapy; Melanoma, Experimental - pathology; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasm Transplantation; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - pathology; Osteosarcoma - drug therapy; Osteosarcoma - pathology; Paclitaxel; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Pharmacology. Drug treatments; Sarcoma, Experimental - drug therapy; Sarcoma, Experimental - pathology; Taxoids; Antineoplastic agent; Intraperitoneal administration; Intravenous administration; Treatment efficiency; Rodentia; Malignant tumor; Route of administration; Biological activity; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Analog; Animal
• ISSN: 0008-5472; 1538-7445

Taxotere (RP 56976; NSC 628503; N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyl taxol) is a new microtubule stabilizing agent. It is obtained by semisynthesis from a noncytotoxic precursor extracted from the needles of the tree, Taxus baccata L. Taxotere was evaluated for antitumor activity against a variety of transplantable tumors of mice. Taxotere had no marked schedule dependency and was found active by the i.v. and the i.p. routes. Upon i.v. administration, 9 of 11 tumor models tested responded to Taxotere. B16 melanoma was found highly sensitive to Taxotere, with a tumor growth inhibition of 0% and a 3.0 log10 tumor cell kill at the maximum tolerated dose. In the same trial, taxol produced only a 1.1 log10 tumor cell kill at the maximum tolerated dose. Taxotere cured early stage pancreatic ductal adenocarcinoma 03 (6 of 6 cures) and colon adenocarcinoma 38 (7 of 7 cures). It also effected greater than 80% complete regressions of advanced stage disease with both tumors. Taxotere was active against early and advanced stage colon adenocarcinoma 51, with 2.3 and 1.7 log10 cell kill, respectively. Four other tumors responded to a lesser extent: Lewis lung (5.5% tumor growth inhibition), Glasgow osteogenic sarcoma (27.2% tumor growth inhibition), L1210 and P388 leukemias (70 and 54% increase in life span, respectively). Because of its good preclinical activity and its unique mechanism of action, Taxotere has entered Phase I clinical trials.