Abstract:
:The population approach has been implemented prospectively in the clinical development of docetaxel (Taxotere). Overall 640 patients were evaluable for the population PK/PD analysis. The PK analysis evidenced significant covariates explaining the inter-patient variability of docetaxel clearance and the PK/PD analysis demonstrated that the variability in clearance was a significant predictor of several safety endpoints. In patients with clinical chemistry suggestive of mild to moderate liver function impairment (SGOT and/or SGPT > 1.5 x ULN concomitant with alkaline phosphatase >2.5 x ULN), total body clearance was lowered by an average of 27%. Specific safety analyses demonstrated that these patients are at a significantly higher risk than others for the development of severe docetaxel-induced side effects. Population PK/PD data were fully integrated into the regulatory dossier and in the labeling of docetaxel worldwide. Population PK/PD models are being used to elaborate a simulation model to predict the survival of patients with non-small cell lung cancer treated with docetaxel.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Bruno R,Vivier N,Veyrat-Follet C,Montay G,Rhodes GRdoi
10.1023/a:1010687017717subject
Has Abstractpub_date
2001-05-01 00:00:00pages
163-9issue
2eissn
0167-6997issn
1573-0646journal_volume
19pub_type
杂志文章,评审abstract::Purpose Among alkaloids, abundant secondary metabolites in plants, aporphines constitute a class of compounds with interesting biological activities, including anticancer effects. The present study evaluated the anticancer activities of 14 substances, including four aporphine derivatives acquired through the biomonito...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-019-00784-6
更新日期:2020-02-01 00:00:00
abstract::Peloruside A is a microtubule-stabilizing agent that is currently under investigation as a potential anticancer agent. Peloruside A binds to a site on β-tubulin that is distinct to that of the taxanes (paclitaxel and docetaxel) and the epothilones. An attractive clinical quality of microtubule-stabilizing agents is th...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-015-0232-8
更新日期:2015-06-01 00:00:00
abstract::Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic melanoma and other cancers and have shown promising results. Inhibition of CTLA-4 characteristically induces well-known side effects called "immune-related adverse ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-014-0092-7
更新日期:2014-08-01 00:00:00
abstract::Receptor tyrosine kinases (RTKs) modulate a variety of cellular events, including cell proliferation, differentiation, mobility and apoptosis. In addition, RTKs have been validated as targets for cancer therapies. Microtubules are another class of proven targets for many clinical anticancer drugs. Here, we report that...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9577-1
更新日期:2012-04-01 00:00:00
abstract::Human topoisomerase II (hTopoII) inhibitors are important chemotherapeutic agents in many different settings including treatment of malignant mesothelioma. Topoisomerase poisons, such as etoposide and doxorubicin, function by trapping the DNA-enzyme covalent complex producing DNA strand breaks which can ultimately lea...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9720-7
更新日期:2012-08-01 00:00:00
abstract::Twenty-four evaluable patients with epithelial ovarian cancer resistant to primary therapy, or relapsing after response to initial therapy, were treated with acivicin utilizing a daily X 5 schedule. One patient achieved a partial response lasting five months; the remaining 23 patients showed no objective response. Pro...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00172016
更新日期:1986-01-01 00:00:00
abstract::Cribrostatin 6 is a quinone-containing natural product that induces the death of cancer cell lines in culture, and its mechanism of action and scope of activity are unknown. Here we show that cribrostatin 6 has broad anticancer activity, potently inducing apoptotic cell death that is not preceded by any defined cell c...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9390-x
更新日期:2011-08-01 00:00:00
abstract::In an on-going Phase II evaluation, dianhydrogalactitol (NSC 132313) was administered intravenously to 28 patients with advanced or recurrent non-squamous cell carcinoma of the cervix. The initial dosage was 60 mg/m2/wk with escalation to 75 mg/m2/wk if there were no adverse effects. Twenty-seven patients were evaluab...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175387
更新日期:1984-01-01 00:00:00
abstract::The current recommendations for Phase I trials should allow more confident interpretation of the toxicity and efficacy of new agents by providing a framework for multicentre and international co-operation. An overview of the aims and designs of Phase I trials is presented, along with a summary of current and recently ...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/BF00173679
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND:Hepatocellular carcinoma (HCC) cells are auxotrophic for arginine, depletion of which leads to tumour regression. The current study evaluated safety, pharmacokinetics (PK)/ pharmacodynamics (PD) parameters, and potential anti-tumor activity of pegylated recombinant human arginase 1 (peg-rhArg1) in advanced H...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9807-9
更新日期:2013-02-01 00:00:00
abstract::Idarubicin, a new analogue of daunorubicin, was administered to 27 patients with advanced breast cancer in a phase II trial. The drug was given orally at a dose of 30-35 mg/m2 every 3 weeks. Twenty-two patients were evaluable for response. All evaluable patients were previously treated with one or more chemotherapeuti...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00172014
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:Gemcitabine (G) has shown activity in mantle cell lymphoma (MCL) as a single agent. The combination of mitoxantrone (M) and rituximab (R) is also active in MCL. The primary objective of this study was to determine the efficacy of G+M+R in relapsed or refractory MCL. PATIENTS AND METHODS:Sixteen patients wer...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-008-9191-7
更新日期:2009-10-01 00:00:00
abstract:PURPOSE:Amrubicin is a novel 9-aminoanthracycline. This multicenter phase II study was conducted to evaluate the efficacy and safety of amrubicin in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:Sixty-one previously untreated patients with stage III or IV NSCLC were entered this study. The pat...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s10637-006-5937-2
更新日期:2006-03-01 00:00:00
abstract::We performed an in-vitro study testing the chemosensitivity of peritoneal cancer cell lines (SW620, HCT116, MKN45, 23,132/87, OAW42) to various cytostatic drug regimens. A duplex drug, characterized by reversible linking of the antimetabolites 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), was compa...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-018-0641-6
更新日期:2019-06-01 00:00:00
abstract::Standard therapy for advanced or metastatic non-small cell lung cancer (NSCLC) has primarily consisted of traditional cytotoxic chemotherapy, although use of targeted therapies has been approved in specific settings. Antiangiogenic agents represent a promising therapeutic strategy for treatment of advanced NSCLC. Beva...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/s10637-011-9750-1
更新日期:2012-08-01 00:00:00
abstract::alpha-Difluoromethylornithine (DFMO) is a known irreversible inhibitor of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Cyclosporine (CsA) has been reported to inhibit ODC activity in vitro. In the present study, we compared the effects of DFMO and CsA on growth, survival, and poly...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175295
更新日期:1987-01-01 00:00:00
abstract::Withaferin A (WA), a steroidal lactone derived from the plant Vassobia breviflora, has been reported to have anti-proliferative, pro-apoptotic, and anti-angiogenic properties against cancer growth. In this study, we identified several key underlying mechanisms of anticancer action of WA in glioblastoma cells. WA was f...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9888-5
更新日期:2013-06-01 00:00:00
abstract::Phosphatidylserine (PS) and other anionic phospholipids, which become exposed on the surface of proliferating endothelial cells, tumor cells and certain leukocytes, have been used as targets for the development of clinical-stage biopharmaceuticals. One of these products (bavituximab) is currently being investigated in...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-015-0248-0
更新日期:2015-08-01 00:00:00
abstract::This study was designed to test the hypothesis that specific inhibition of cathepsins B and L will cause death of neuroblastoma cells. Five compounds that differ in mode and rate of inhibition of these two enzymes were all shown to cause neuroblastoma cell death. Efficacy of the different compounds was related to thei...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9826-6
更新日期:2013-02-01 00:00:00
abstract::Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib tre...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-015-0284-9
更新日期:2015-10-01 00:00:00
abstract::We have recently developed a liposomal nanoparticle (LNP) formulation of irinotecan based on loading method that involves formation of a complex between copper and the water soluble camptothecin. The loading methodology developed for irinotecan was evaluated to develop a LNP topotecan formulation (referred to herein a...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9832-8
更新日期:2013-02-01 00:00:00
abstract::HDAC inhibitors (HDACI) are now emerging as one of the most promising new classes of drugs for the treatment of select forms of non-Hodgkin's lymphoma (NHL). They are particularly active in T-cell lymphomas, possibly hodgkin's lymphoma and indolent B cell lymphomas. Presently, two of these agents, vorinostat and romid...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9591-3
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND:BTH1677 is a beta glucan pathogen associated molecular pattern (PAMP) currently being investigated as a novel cancer therapy. Here, the initial safety and pharmacokinetic (PK) results of BTH1677 in healthy subjects are reported. SUBJECTS AND METHODS:In the Phase 1a single-dosing study, subjects were randomi...
journal_title:Investigational new drugs
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10637-016-0325-z
更新日期:2016-04-01 00:00:00
abstract::Background High-risk neuroblastoma has poor outcomes with high rates of relapse despite aggressive treatment, and novel therapies are needed to improve these outcomes. Ponatinib is a multi-tyrosine kinase inhibitor that targets many pathways implicated in neuroblastoma pathogenesis. We hypothesized that ponatinib woul...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-016-0387-y
更新日期:2016-12-01 00:00:00
abstract::Fourteen patients with acute leukemia in relapse were treated with difluoromethylornithine (DFMO) alone or in combination with methylglyoxal-bis(guanylhydrazone) (MGBG) as part of Phase I studies. Five patients included in the trial exhibited morphologic evidence of cellular differentiation during the course of treatm...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00170848
更新日期:1989-07-01 00:00:00
abstract::Neuroblastoma is an extracranial, solid, and heterogeneous malignancy in children. The conventional therapeutic modalities are mostly ineffective and thus new therapeutic strategies for malignant neuroblastoma are urgently warranted. We examined the synergistic efficacy of combination of sorafenib (SF) and genistein (...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9324-7
更新日期:2010-12-01 00:00:00
abstract::Background PF-06650808 is a novel anti-Notch3 antibody-drug conjugate (ADC) able to deliver an auristatin-based cytotoxic payload to target cells. In this first-in-human, dose-finding, phase I study (NCT02129205), we investigated safety, pharmacokinetics, immunogenicity, and preliminary antitumor activity of single-ag...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10637-019-00754-y
更新日期:2020-02-01 00:00:00
abstract::Angiogenesis is recognized as an important biological process that allows growth of a tumor beyond an initial small size. PTK787/ZK222584, a potent orally active angiogenesis inhibitor capable of inhibiting all known isoforms of Vascular Endothelial Growth Factor (VEGF) receptor, belongs to the class of aminophthalazi...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9157-9
更新日期:2009-02-01 00:00:00
abstract::The anti-tumor properties of novel derivatives prepared from Aconitum C(20)-diterpenoid alkaloid, which show the least toxicity among the Aconitum alkaloids, were investigated in the Non-Hodgkin's lymphoma cell line Raji cells. Two novel Aconitum C(20)-diterpenoid alkaloid derivatives, 11-m-Trifluorometylbenzoyl (Mb)-...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9327-4
更新日期:2011-02-01 00:00:00
abstract::Glioblastoma (GBM), one of the most malignant human neoplasias, responds poorly to current treatment modalities, with temozolomide (TMZ) being the drug most frequently used for its treatment. Tetra-O-methyl Nordihydroguaiaretic Acid (M4N) is a global transcriptional repressor of genes dependent on the Sp1 transcriptio...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9917-4
更新日期:2013-08-01 00:00:00