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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(More)
The anti-tumour activity of CPT-11, a topoisomerase I inhibitor, was evaluated in four human neural-crest-derived paediatric tumour xenografts; one peripheral primitive neuroectodermal tumour (pPNET) (SK-N-MC) and three neuroblastomas. Two models, SK-N-MC and IGR-N835, were established in athymic mice from a previously established in vitro cell line. Two(More)
Docetaxel is a new taxoid with clinical activity in breast and lung cancer. Using docetaxel-sensitive and -refractory mammary and pancreatic murine tumours, as well as human-derived neoplasms, we investigated if a determinant of docetaxel sensitivity could be found at the level of its mechanism of action. Because microtubules represent the cellular targets(More)
Docetaxel tolerance and antitumor efficacy could be enhanced if drug administration was adapted to circadian rhythms. This hypothesis was investigated in seven experiments involving a total of 626 male B6D2F1 mice, synchronized with an alternation of 12 h of light and 12 h of darkness (12:12), after i.v. administration of docetaxel. In experiment (Exp) 1,(More)
Docetaxel is a taxoid which is currently in phase II/III clinical trials in Europe, the US and Japan. It was found to promote tubulin assembly in microtubules and to inhibit their depolymerization. In vitro, the docetaxel concentrations required to reduce murine and human cell survival by 50% ranged from 4 to 35 ng/ml and the cytotoxic effects were greater(More)
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(More)
A series of new 3'-(2-methyl-1-propenyl) and 3'-(2-methylpropyl) taxoids with modifications at C-10 was synthesized by means of the beta-lactam synthon method using 10-modified 7-(triethylsilyl)-10-deacetylbaccatin III derivatives. The new taxoids thus synthesized show excellent cytotoxicity against human ovarian (A121), non-small-cell lung (A549), colon(More)
The efficacy of the topoisomerase I inhibitor CPT-11 [7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxycamptothec in] has been evaluated against a panel of human tumor xenografts derived from adult and pediatric malignancies. Tumors included eight colon adenocarcinomas representing intrinsically chemorefractory malignancies, six lines derived from(More)
Progress in cancer chemotherapy has been made owing to the discovery and development of drugs that have new structures, new mechanisms of action, and high levels of experimental antitumor activity. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) is prepared by semisynthesis from 10-deacetyl baccatin III, an inactive taxoid precursor extracted from(More)
The therapeutic index of docetaxel, doxorubicin and their combination may be improved by an adequate selection of the circadian time of administration. The present study constitutes a prerequisite to testing the clinical relevance of chronotherapy in human breast cancer. Three experiments were performed in C3H/HeN mice. Each treatment modality was(More)