Journal ArticleDOI
Docetaxel (Taxotere): a review of preclinical and clinical experience. Part I: Preclinical experience.
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TLDR
In vivo, the drug was found to be schedule independent and 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 on proliferating than on non-proliferating cells.Abstract:
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 on proliferating than on non-proliferating cells. It was also found to be cytotoxic on fresh human tumor biopsies. In vivo, the drug was found to be schedule independent. A total of 13/14 murine transplantable tumors were found very sensitive to i.v. docetaxel and complete regressions of advanced stage tumors were obtained. Activity was also observed in 15/16 human tumor xenografts in nude mice at an advanced stage. In combination studies, synergism was observed in vivo with 5-fluorouracil, cyclophosphamide and etoposide. Pharmacokinetic evaluation revealed linear pharmacokinetics in tumor-bearing mice. There was a good tumor retention with a 22 h elimination half-life. Plasma protein binding ranged from 76 to 89%. Preclinical toxicology evaluation of docetaxel included single-dose toxicity in rats, mice and dogs, 5-day toxicity in mice and dogs, intermittent-dose toxicity in rats, dogs and monkeys, genetic and reproductive toxicity, as well as investigation of the irritation and sensitization potential. The principal toxicities were hematopoietic (all species), gastrointestinal (dog, monkey) and neuromotor (mice). Dogs appeared to be the most sensitive species. The clinical entry dose of 5 mg/m2 was based on one-third of the 'toxic dose low' in dogs (15 mg/m2).read more
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Journal ArticleDOI
Cancer Nanotechnology: The impact of passive and active targeting in the era of modern cancer biology
TL;DR: The fundamental concepts of enhanced permeability and retention effect (EPR) are revisited and the mechanisms proposed to enhance preferential "retention" in the tumor, whether using active targeting of nanoparticles, binding of drugs to their tumoral targets or the presence of tumor associated macrophages are explored.
Journal ArticleDOI
Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile
Jeffrey S. Hrkach,Daniel D. Von Hoff,Mir Mukkaram Ali,Elizaveta Andrianova,Jason Auer,Tarikh Christopher Campbell,David De Witt,Michael Figa,Maria Figueiredo,Allen Horhota,Susan Low,Kevin McDonnell,Erick Peeke,Beadle Retnarajan,Abhimanyu Sabnis,Edward Schnipper,Jeffrey J. Song,Young-Ho Song,Jason Summa,Douglas Tompsett,Greg Troiano,Tina Van Geen Hoven,James Wright,Patricia LoRusso,Philip W. Kantoff,Neil H. Bander,Christopher Sweeney,Omid C. Farokhzad,Robert Langer,Stephen E. Zale +29 more
TL;DR: Developing and clinical translation of a targeted polymeric nanoparticle (TNP) containing the chemotherapeutic docetaxel (DTXL) for the treatment of patients with solid tumors and initial clinical data indicated that DTXL-TNP displays a pharmacological profile differentiated from sb-DTXL.
Journal ArticleDOI
The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents
TL;DR: This review describes the preclinical features and clinical results of the two major taxanes, paclitaxel (Taxol, Bristol-Myers Squibb) and docetaxe (Taxotere, Rhone-Poulenc Rhorer).
Journal ArticleDOI
Phase III Randomized Trial of Docetaxel–Carboplatin Versus Paclitaxel–Carboplatin as First-line Chemotherapy for Ovarian Carcinoma
Paul Vasey,Gordon C Jayson,Alan N. Gordon,Hani Gabra,Robert E. Coleman,Ronnie Atkinson,David E. Parkin,James Paul,A. Hay,Stan B. Kaye +9 more
TL;DR: In this article, the authors compared the combination of docetaxel-carboplatin and paclitaxel carboplatin as first-line chemotherapy for stage Ic-IV epithelial ovarian or primary peritoneal cancer.
Journal ArticleDOI
Randomized Phase III Study of Docetaxel Compared With Paclitaxel in Metastatic Breast Cancer
Stephen E. Jones,John K. Erban,Beth Overmoyer,G.T. Budd,L. Hutchins,Elyse E. Lower,L. Laufman,S. Sundaram,Walter J. Urba,Kathleen I. Pritchard,R. Mennel,D. Richards,S. Olsen,M.L. Meyers,Peter M. Ravdin +14 more
TL;DR: Docetaxel was superior to paclitaxel in terms of OS and TTP and the overall response rate (ORR) was higher for docetaxe than for pac litaxel.
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