当前位置： SCI文献检索 > INVESTIGATIONAL NEW DRUGS期刊下所有文献 > A phase I study of DHP107, a mucoadhesive lipid form of oral paclitaxel, in patients with advanced solid tumors: crossover comparisons with intravenous paclitaxel.

A phase I study of DHP107, a mucoadhesive lipid form of oral paclitaxel, in patients with advanced solid tumors: crossover comparisons with intravenous paclitaxel.

Abstract：

PURPOSE:This study investigated the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetic (PK) profiles of DHP107, a novel oral paclitaxel containing neither Cremophor EL nor P-glycoprotein (P-gp) inhibitor. PATIENTS AND METHODS:Patients with advanced solid tumors refractory to all standard treatments were administered a single oral dose of DHP107 on a dose-escalating schedule (60-600 mg/m(2)) during the first chemotherapy cycle, and intravenous paclitaxel 175 mg/m(2) during subsequent cycles. Cohorts of 3 patients were treated at each dose level provided no DLTs were observed. The pharmacokinetics of paclitaxel and its metabolites were investigated for oral DHP107 and intravenous paclitaxel. RESULTS:Thirty-four patients were enrolled. Dose-limiting toxicities were not observed, even at the highest dose level (600 mg/m(2)). Further dose escalation was not performed because pharmacokinetics did not increase proportionally at doses above 250 mg/m(2). The coefficient of variance of AUClast DHP107 ranged from 11.8 % to 34.0 %, comparable to 24.4 % of intravenous paclitaxel 175 mg/m(2). There were no grade 4 toxicities, whereas grade 3 toxicities included diarrhea (12.1 %), neutropenia (6.1 %) and fatigue (3.0 %). While no objective responses were observed, 11 patients (33.3 %) showed stable disease. CONCLUSIONS:DHP107 was safe and feasible in patients with advanced malignancies. As exposure of paclitaxel plateau among patients receiving more than 250 mg/m(2) of DHP107, the dose escalation of DHP107 may be limited to 250 mg/m(2) in further clinical trials.

journal_name

Invest New Drugs

journal_title

Investigational new drugs

authors

Hong YS,Kim KP,Lim HS,Bae KS,Ryu MH,Lee JL,Chang HM,Kang YK,Kim H,Kim TW

doi

10.1007/s10637-012-9841-7

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

616-22

issue

3

eissn

0167-6997

issn

1573-0646

journal_volume

31

pub_type

杂志文章

相关文献

INVESTIGATIONAL NEW DRUGS文献大全
  • Perifosine selectively induces cell cycle block and modulates retinoblastoma and E2F1 protein levels in p53 mutated leukemic cell lines.

    abstract：:The effect of the single-chain alkylphospholipid perifosine was analyzed in p53(wild-type) (SKW6.4, OCI and MOLM), p53(mutated) (BJAB, MAVER) and p53(null) (HL-60) leukemic cell lines. Perifosine promoted cytotoxicity with a combination of apoptosis induction in all cell lines and cell cycle block at the G(2)M checkpo...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-009-9370-1

    authors： Celeghini C,Voltan R,Rimondi E,Gattei V,Zauli G

    更新日期：2011-04-01 00:00:00

  • Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours.

    abstract：AIM:To quantify the effect of food on the systemic exposure of lapatinib at steady state when administered 1 h before and after meals, and to observe the safety and tolerability of lapatinib under these conditions in patients with advanced solid tumours. METHODS:This was a three-treatment, randomised, three-sequence c...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,随机对照试验

    doi：10.1007/s10637-013-0055-4

    authors： Devriese LA,Koch KM,Mergui-Roelvink M,Matthys GM,Ma WW,Robidoux A,Stephenson JJ,Chu QS,Orford KW,Cartee L,Botbyl J,Arya N,Schellens JH

    更新日期：2014-06-01 00:00:00

  • A phase 1 dose-escalating study of pegylated recombinant human arginase 1 (Peg-rhArg1) in patients with advanced hepatocellular carcinoma.

    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

    authors： Yau T,Cheng PN,Chan P,Chan W,Chen L,Yuen J,Pang R,Fan ST,Poon RT

    更新日期：2013-02-01 00:00:00

  • Early depth of tumor shrinkage and treatment outcomes in non-small cell lung cancer treated using Nivolumab.

    abstract：:Background It would be useful to have criteria for predicting long-term treatment responses to immune checkpoint inhibitors (ICIs). Maximum depth of response correlates with treatment outcomes among patients receiving programmed death protein 1 axis inhibitors for non-small cell lung cancer (NSCLC). We investigated as...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-019-00770-y

    authors： Kawachi H,Fujimoto D,Morimoto T,Hosoya K,Sato Y,Kogo M,Nagata K,Nakagawa A,Tachikawa R,Tomii K

    更新日期：2019-12-01 00:00:00

  • The activity of flavone acetic acid (NSC 347512) on human colon cancer cells in vitro.

    abstract：:Flavone acetic acid (FAA) was incubated for 1 to 48 hr with 3 established human colon cancer cell lines endowed with distinct degrees of phenotypic properties. All 3 lines responded to FAA in almost identical fashion; when incubated with the drug for only 1 hr, an initial decrease in survival was observed for concentr...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00173501

    authors： Drewinko B,Yang LY

    更新日期：1986-01-01 00:00:00

  • High dose chemotherapy with autologous marrow rescue in the treatment of resistant solid tumors.

    abstract：:Toxicity in the form of marrow suppression has hampered the investigation of intensive chemotherapy as it applies to the treatment of solid tumors. The use of autologous marrow rescue to ameliorate protracted aplasia permits the application of high dose chemotherapy to the treatment of solid tumors. We review the theo...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,评审

    doi：10.1007/BF00177416

    authors： LeMaistre CF,Knight WA 3rd

    更新日期：1983-01-01 00:00:00

  • Phase I trials in paediatric oncology--the European perspective. The New Agents Group of the United Kingdom Childrens Cancer Study Group.

    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

    authors： Estlin EJ,Ablett S,Newell DR,Lewis IJ,Lashford L,Pearson AD

    更新日期：1996-01-01 00:00:00

  • The flavonoid luteolin suppresses infantile hemangioma by targeting FZD6 in the Wnt pathway.

    abstract：:Infantile hemangioma is the most common vascular tumor of childhood. It is characterized by clinical expansion of endothelial cells and promoted by angiogenic factors. Luteolin is a flavonoid compound that carries anti-cancer and anti-angiogenesis properties. The study aimed to investigate the effect of luteolin in tr...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-020-01052-8

    authors： Dai Y,Zheng H,Liu Z,Wang Y,Hu W

    更新日期：2021-01-07 00:00:00

  • The molecular mechanism of anticancer action of novel octahydropyrazino[2,1-a:5,4-a']diisoquinoline derivatives in human gastric cancer cells.

    abstract：:Objective The aim of the current study was to examine the anticancer activity and the detailed mechanism of novel diisoquinoline derivatives in human gastric cancer cells (AGS). Methods The viability of AGS cells was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell cycle analy...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-018-0584-y

    authors： Pawłowska N,Gornowicz A,Bielawska A,Surażyński A,Szymanowska A,Czarnomysy R,Bielawski K

    更新日期：2018-12-01 00:00:00

  • Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer.

    abstract：PURPOSE:This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. EXPERIMENTAL DESIGN:This was an open-label, multicenter, dose-escalation stu...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-012-9815-9

    authors： Weiss GJ,Donehower RC,Iyengar T,Ramanathan RK,Lewandowski K,Westin E,Hurt K,Hynes SM,Anthony SP,McKane S

    更新日期：2013-02-01 00:00:00

  • Two-stage model-based clinical trial design to optimize phase I development of novel anticancer agents.

    abstract：BACKGROUND:The phase I program of anticancer agents usually consists of multiple dose escalation studies to select a safe dose for various administration schedules. We hypothesized that pharmacokinetic and pharmacodynamic (PK-PD) modeling of an initial phase I study (stage 1) can be used for selection of an optimal sta...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-008-9216-2

    authors： Zandvliet AS,Karlsson MO,Schellens JH,Copalu W,Beijnen JH,Huitema AD

    更新日期：2010-02-01 00:00:00

  • N-Methylformamide in advanced squamous cancer of the uterine cervix: an Eastern Cooperative Oncology Group phase II trial.

    abstract：PURPOSE:Preclinical and clinical data support the study of polar-planar compounds such as N-Methylformamide (NMF) in advanced squamous cell carcinoma of the uterine cervix (SCC). This phase II trial sought to determine the efficacy and toxicities of NMF in patients with advanced SCC. PATIENTS AND METHODS:Eligibility f...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章,多中心研究

    doi：10.1023/a:1010672618269

    authors： Rajdev L,Yu ZF,Wadler S,Weller E,Kahn SB,Tormey D,Skeel R,Wiernik PH

    更新日期：2001-01-01 00:00:00

  • Effect of ketoconazole on the pharmacokinetics of axitinib in healthy volunteers.

    abstract：OBJECTIVE:Axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, is metabolized primarily by cytochrome P450 (CYP) 3A with minor contributions from CYP1A2, CYP2C19, and glucuronidation. Co-administration with CYP inhibitors may increase systemic expos...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,随机对照试验

    doi：10.1007/s10637-010-9511-6

    authors： Pithavala YK,Tong W,Mount J,Rahavendran SV,Garrett M,Hee B,Selaru P,Sarapa N,Klamerus KJ

    更新日期：2012-02-01 00:00:00

  • Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced hepatocellular carcinoma.

    abstract：UNLABELLED:Although UFT 300 mg/m2/day and leucovorin 90 mg/day administered orally in divided doses administered every 8 hours for 28 days repeated every 35 days could be administered safely to patients with advanced hepatomas and good performance status, this combination and schedule has limited activity in treating a...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1023/a:1006104217137

    authors： Mani S,Schiano T,Garcia JC,Ansari RH,Samuels B,Sciortino DF,Tembe S,Shulman KL,Baker A,Benner SE,Vokes EE

    更新日期：1998-01-01 00:00:00

  • Effective upfront treatment with low-dose ibrutinib for a patient with B cell prolymphocytic leukemia.

    abstract：:B cell prolymphocytic leukemia (B-PLL) is a rare and aggressive disease that is associated with poor survival. Although initially asymptomatic patients do not require therapy, most patients will progress and inevitably require treatment. More than 50% of patients with B-PLL carry abnormalities in the TP53 tumor suppre...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-020-00902-9

    authors： Oka S,Ono K,Nohgawa M

    更新日期：2020-10-01 00:00:00

  • Crizotinib-induced simultaneous multiple cardiac toxicities.

    abstract：:Crizotinib is a receptor tyrosine kinase inhibitor that has several targets, including c-ros oncogene 1 and the MET proto-oncogene. Considering its known cardiac toxicity, bradycardia is often investigated following treatment with crizotinib. Our patients had bradycardia, QT prolongation, ventricular rhythm, ventricul...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-018-0605-x

    authors： Oyakawa T,Muraoka N,Iida K,Kusuhara M,Kawamura T,Naito T,Takahashi T

    更新日期：2018-10-01 00:00:00

  • Prolonged infusion gemcitabine: a clinical phase I study at low- (300 mg/m2) and high-dose (875 mg/m2) levels.

    abstract：:Gemcitabine (GEM) is a novel nucleoside analogue with a unique mechanism of action. Preliminary studies have shown a mild, schedule-dependent toxic profile with a broad range of MTDs and promising antitumor activity in various solid tumors. This phase I study describes the infusion length-effect relationships of low- ...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1023/a:1005817024382

    authors： Pollera CF,Ceribelli A,Crecco M,Oliva C,Calabresi F

    更新日期：1997-01-01 00:00:00

  • Effects of drug efflux proteins and topoisomerase I mutations on the camptothecin analogue gimatecan.

    abstract：:Clinically relevant resistance to the currently approved camptothecins, irinotecan and topotecan, is poorly understood but may involve increased expression of ATP-dependent drug transporters such as ABCG2 (breast cancer resistant protein, BCRP). Gimatecan (ST1481) is a lipophilic 7-substituted camptothecin derivative ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-007-9093-0

    authors： Gounder MK,Nazar AS,Saleem A,Pungaliya P,Kulkarni D,Versace R,Rubin EH

    更新日期：2008-06-01 00:00:00

  • A phase II study of tandutinib (MLN518), a selective inhibitor of type III tyrosine receptor kinases, in patients with metastatic renal cell carcinoma.

    abstract：:Therapies which target VEGF and mTOR are now available for patients with metastatic renal cell carcinoma, but there is a continued need to develop agents for patients who become refractory to these initial agents. Tandutinib is a relatively selective inhibitor of type III tyrosine kinase receptor kinases with promisin...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-010-9516-1

    authors： Shepard DR,Cooney MM,Elson P,Bukowski RM,Dreicer R,Rini BI,Garcia JA

    更新日期：2012-02-01 00:00:00

  • Matrix metalloproteinase inhibitors: present achievements and future prospects.

    abstract：:Matrix metalloproteinases (MMPs) are a class of structurally related enzymes that function in the degradation of extracellular matrix proteins that constitute the pericellular connective tissue and play an important role in both normal and pathological tissue remodelling. Increased MMP activity is detected in a wide r...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,评审

    doi：10.1023/a:1005855905442

    authors： Denis LJ,Verweij J

    更新日期：1997-01-01 00:00:00

  • Lack of effects of recombinant human interleukin-4 on in vitro colony formation of freshly explanted human tumor cells.

    abstract：:Interleukin-4 is a highly pleiotropic T-cell derived lymphokine that has been reported to stimulate a host cell-mediated antitumor response. Recombinant human interleukin-4 (rhuIL-4) is currently undergoing clinical phase I trials. We have studied the growth modulating effects of rhuIL-4 on a variety of freshly explan...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00944180

    authors： Hanauske AR,Degen D,Marshall MH,Trotta PP,Von Hoff DD

    更新日期：1992-11-01 00:00:00

  • Safety, tolerability and pharmacokinetics of the fibroblast growth factor receptor inhibitor AZD4547 in Japanese patients with advanced solid tumours: a Phase I study.

    abstract：:Background AZD4547 is a potent, oral, highly selective fibroblast growth factor receptor (FGFR) inhibitor in clinical development for treating tumours with a range of FGFR aberrations, including FGFR mutations, amplifications and fusions. Methods This open-label, Phase I, multicentre study (NCT01213160) evaluated the ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s10637-016-0416-x

    authors： Saka H,Kitagawa C,Kogure Y,Takahashi Y,Fujikawa K,Sagawa T,Iwasa S,Takahashi N,Fukao T,Tchinou C,Landers D,Yamada Y

    更新日期：2017-08-01 00:00:00

  • Phase 1 study of the oral histone deacetylase inhibitor abexinostat in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, or chronic lymphocytic leukaemia.

    abstract：:Background We determined the safety, pharmacokinetics, pharmacodynamics, and antitumour activity of abexinostat in B-cell lymphoma or chronic lymphocytic leukaemia. Patients and methods Thirty-five patients received oral abexinostat 30, 45, or 60 mg/m(2) bid in a 3 + 3 design in three 21-day schedules: 14 days on trea...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-015-0206-x

    authors： Morschhauser F,Terriou L,Coiffier B,Bachy E,Varga A,Kloos I,Lelièvre H,Sarry AL,Depil S,Ribrag V

    更新日期：2015-04-01 00:00:00

  • Durable response to the ALK inhibitor alectinib in inflammatory myofibroblastic tumor of the head and neck with a novel SQSTM1-ALK fusion: a case report.

    abstract：:An inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that typically develops in the lungs and seldom in the head and neck region. It is often related to the anaplastic lymphoma kinase (ALK) fusion gene. Crizotinib, a first-generation ALK inhibitor, has been shown to have a notable response in pat...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-019-00742-2

    authors： Honda K,Kadowaki S,Kato K,Hanai N,Hasegawa Y,Yatabe Y,Muro K

    更新日期：2019-08-01 00:00:00

  • Phase 1b study of the oral gemcitabine 'Pro-drug' LY2334737 in combination with capecitabine in patients with advanced solid tumors.

    abstract：:Background This Phase 1b study aimed to determine the recommended Phase 2 dose of LY2334737, an oral pro-drug of gemcitabine, in combination with capecitabine, an oral pro-drug of 5-fluorouracil, in patients with advanced solid tumors. In addition, pharmacokinetics (PK) and tumor response were evaluated. Patients and ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-015-0207-9

    authors： Infante JR,Benhadji KA,Dy GK,Fetterly G,Ma WW,Bendell J,Callies S,Adjei AA

    更新日期：2015-04-01 00:00:00

  • Contributions from emerging transcriptomics technologies and computational strategies for drug discovery.

    abstract：:Drug discovery involves various steps and is a long process being even more demanding for complex diseases such as cancer. Tumors are ensembles of subpopulations with different mutations, require very specific and effective strategies. Conventional drug screening technologies may not be adequate and efficient anymore....

    journal_title：Investigational new drugs

    pub_type： 杂志文章,评审

    doi：10.1007/s10637-014-0081-x

    authors： Kadioglu O,Efferth T

    更新日期：2014-12-01 00:00:00

  • Luteolin inhibits cell proliferation during Azoxymethane-induced experimental colon carcinogenesis via Wnt/ β-catenin pathway.

    abstract：:The protective role of Luteolin (LUT) against Azoxymethane (AOM)-induced mouse colon carcinogenesis has been documented earlier. The aim of this study is to investigate on the mechanism of chemopreventive action exhibited by LUT employing AOM-induced colon carcinogenesis in mice as an experimental model. LUT inhibited...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-009-9359-9

    authors： Ashokkumar P,Sudhandiran G

    更新日期：2011-04-01 00:00:00

  • Growth inhibition induced by antiprogestins RU-38486, ORG-31710, and CDB-2914 in ovarian cancer cells involves inhibition of cyclin dependent kinase 2.

    abstract：:Antiprogestins have been largely utilized in reproductive medicine, yet their repositioning for oncologic use is rapidly emerging. In this study we investigated the molecular mediators of the anti-ovarian cancer activity of the structurally related antiprogestins RU-38486, ORG-31710 and CDB-2914. We studied the respon...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-011-9655-z

    authors： Goyeneche AA,Seidel EE,Telleria CM

    更新日期：2012-06-01 00:00:00

  • Silibinin ameliorates oxidative stress induced aberrant crypt foci and lipid peroxidation in 1, 2 dimethylhydrazine induced rat colon cancer.

    abstract：:Pharmacological intervention to reduce CRC mortality entails the use of oral agents that can avert carcinogenesis. Silibinin, a major component of silymarin isolated from Silybum marianum (L.) was found to possess attractive remedial features. An in vivo study was designed to elucidate the effect of silibinin on the f...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-009-9237-5

    authors： Sangeetha N,Aranganathan S,Nalini N

    更新日期：2010-06-01 00:00:00

  • Circulating vascular endothelial growth factor receptor 2/pAkt-positive cells as a functional pharmacodynamic marker in metastatic colorectal cancers treated with antiangiogenic agent.

    abstract：OBJECTIVE:The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has received considerable attention as a first-line treatment of advanced colorectal cancers. Difficulties associated with effectively monitoring the activity of this drug have prompted us to seek a pharmacodynamic marker suitable for def...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-012-9817-7

    authors： Shin SJ,Hwang JW,Ahn JB,Rha SY,Roh JK,Chung HC

    更新日期：2013-02-01 00:00:00