Maurizio Rocchetti

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The available mathematical models describing tumor growth and the effect of anticancer treatments on tumors in animals are of limited use within the drug industry. A simple and effective model would allow applying quantitative thinking to the preclinical development of oncology drugs. In this article, a minimal pharmacokinetic-pharmacodynamic model is(More)
A mathematical model for describing the cancer growth dynamics in response to anticancer agents administration in xenograft models is discussed. The model consists of a system of ordinary differential equations involving five parameters (three for describing the untreated growth and two for describing the drug action). Tumor growth in untreated animals is(More)
PHA-739358 is a small-molecule 3-aminopyrazole derivative with strong activity against Aurora kinases and cross-reactivities with some receptor tyrosine kinases relevant for cancer. PHA-739358 inhibits all Aurora kinase family members and shows a dominant Aurora B kinase inhibition-related cellular phenotype and mechanism of action in cells in vitro and in(More)
PURPOSE This study was conducted to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the i.v. pan-aurora kinase inhibitor PHA-739358, danusertib, in patients with advanced solid tumors. EXPERIMENTAL DESIGN In part 1, patients received escalating doses of danusertib (24-hour infusion every 14 days) without filgrastim (granulocyte(More)
The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives toward the inhibition of Aurora kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora kinases that also shows low nanomolar potency against additional anticancer kinase targets. Based on its high antiproliferative activity on(More)
The preclinical development of antitumor drugs greatly benefits from the availability of models capable of predicting tumor growth as a function of the drug administration schedule. For being of practical use, such models should be simple enough to be identifiable from standard experiments conducted on animals. In the present paper, a stochastic model is(More)
The success rate of clinical drug development is significantly lower in oncology than in other therapeutic areas. Predicting the activity of new compounds in humans from preclinical data could substantially reduce the number of failures. A novel approach for predicting the expected active doses in humans from the first animal studies is presented here. The(More)
In clinical oncology, combination regimens may result in a synergistic, additive or antagonistic interaction (i.e. the effect of the combination is greater, similar or smaller than the sum of the effects of the individual compounds). For this reason, during the drug development process, in vivo pre-clinical studies are performed to assess the interaction of(More)
Intravenous administration of paclitaxel is hindered by poor water solubility of the drug. Currently, paclitaxel is dissolved in a mixture of ethanol and Cremophor EL; however, this formulation (Taxol) is associated with significant side effects, which are considered to be related to the pharmaceutical vehicle. A new polymer-conjugated derivative of(More)
Polo-like kinase 1 (Plk1) is a fundamental regulator of mitotic progression whose overexpression is often associated with oncogenesis and therefore is recognized as an attractive therapeutic target in the treatment of proliferative diseases. Here we discuss the structure-activity relationship of the 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline class of(More)