Abstract:
:The diarylsulfonylureas have shown promise in xenograft models of childhood cancer. Sulofenur has been evaluated in phase I and II trials in adults with a variety of solid tumors, but the toxicity and maximum tolerated dose of sulofenur in children and adolescents have not been determined. In a phase I study, sulofenur was administered to 13 patients with refractory pediatric malignant solid tumors. Daily dosages of 640, 800, and 960 mg/M2 in two divided oral doses were given for 5 consecutive days each week for 3 weeks. The primary and dose-limiting toxicity was methemoglobinemia, which occurred at all dose levels and required transfusions of packed red blood cells, administration of methylene blue, or both. Anemia and, less frequently, leukopenia and thrombocytopenia were also observed. A maximum tolerated daily dosage was not defined, as methemoglobinemia was noted with each dosage level. There were no measurable tumor responses. The toxicity of this agent makes it unattractive for further investigation in pediatric patients.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Pratt CB,Bowman LC,Marina N,Pappo A,Avery L,Luo X,Meyer WHdoi
10.1007/BF02614222subject
Has Abstractpub_date
1995-01-01 00:00:00pages
63-6issue
1eissn
0167-6997issn
1573-0646journal_volume
13pub_type
临床试验,杂志文章abstract::Pre-clinical and clinical studies have shown that trifluoperazine (TFP) can modulate multidrug resistance. We have performed a Phase II trial of TFP and doxorubicin in doxorubicin-naive patients with metastatic breast cancer. We hypothesized that TFP would inhibit the development of doxorubicin resistance, resulting i...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00873916
更新日期:1993-02-01 00:00:00
abstract::To explore the clinical significance of the level of HER2/neu gene amplification in a homogenous cohort of 33 patients with HER2-positive metastatic breast cancer (MBC) and available tumor samples treated with a trastuzumab-based regimen, we retrospectively performed dual-color fluorescence in-situ hybridization test ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9155-y
更新日期:2009-04-01 00:00:00
abstract::9-Aminocamptothecin (9-AC) is a water-insoluble camptothecin derivative that demonstrated broad activity in pre-clinical studies. In vitro, greater anti-tumor efficacy can be achieved with prolonged administration. A minor response was observed in gastric cancer in a phase I study. We conducted a phase II study of 9-A...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1023/B:DRUG.0000026259.28395.c2
更新日期:2004-08-01 00:00:00
abstract::Purpose The aim of this study is to detect apoptotic and cytotoxic/antiproliferative effects of a ligand substance and its metal derivatives. The substances were investigated by using an h-ras oncogene transformed rat embryo fibroblast cell line (5RP7). Methods The cytotoxic influences of dipyrido[3,2-a:2',3'c]phenazi...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0559-4
更新日期:2018-10-01 00:00:00
abstract:PURPOSE:Hepatobiliary cancers respond poorly to cytotoxic chemotherapy. We evaluated the activity and safety of ixabepilone, an epothilone B analogue which stabilizes microtubules, in a phase II trial in patients with advanced cancers of the gallbladder, bile duct, and liver. METHODS:Eligible patients had previously-u...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9297-6
更新日期:2010-12-01 00:00:00
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
更新日期:2018-10-01 00:00:00
abstract::An in vitro assay, which evaluates drug effect on 3H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activiti...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175294
更新日期:1987-01-01 00:00:00
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
更新日期:2014-12-01 00:00:00
abstract::Mitoxantrone (Novantrone; 1, 4-dihydroxy-5, 8-bis [[2-[(2-hydroxyethyl) amino]ethyl]amino-] 9, 10 anthracenedione dihydrochloride (NSC 301739] is a synthetic anthracenedione with intercalating properties. Activity has been shown in preclinical studies in mice bearing intraperitoneal P388 and L1210 leukaemias, ADJ-Pc6 ...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00174172
更新日期:1985-01-01 00:00:00
abstract::Background Metformin use is associated with reduced cancer risk in epidemiological studies and has preclinical anti-cancer activity in ovarian cancer models. The primary objective of this phase I study was to determine the recommended phase II dose (RP2D) of metformin in combination with carboplatin/paclitaxel in pati...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-00920-7
更新日期:2020-10-01 00:00:00
abstract::Major discrepancies concerning risk-benefit assessments and regulatory actions are frequent among regulatory agencies. We explored the differences by scrutinizing a case of gemtuzumab ozogamicin (GO) in patients with acute myeloid leukaemia (AML). Assessment reports of GO were retrieved form the websites of the US Foo...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/s10637-012-9877-8
更新日期:2013-04-01 00:00:00
abstract::Nafazatrom was tested against a variety of human malignancies with the human tumor stem cell assay at one or more of the following concentrations: 1, 10, 25, and 100 micrograms/ml X 1 h or 0.05, 0.5, or 5 micrograms/ml by continuous exposure. Major (greater than or equal to 70%) inhibition was noted in 7/52 adenocarci...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00173781
更新日期:1984-01-01 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::Thirty-two patients with advanced epidermoid carcinoma of the esophagus were treated with ifosfamide (1.50 gm/m2 daily x 5 days) with uroprotective mesna in a phase II study. Eighteen patients were previously untreated. Of 28 evaluable patients, two (7%) had partial remissions lasting 2+ and 6+ months. Toxicity was pr...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175406
更新日期:1988-09-01 00:00:00
abstract::Bryostatin 1 (Bryo) is a naturally occurring macrocyclic lactone with antineoplastic activity. Like the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) it directly activates the calcium- and phospholipid-dependent protein kinase C (PKC), thus generating a number of different cellular responses. We investigat...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00873230
更新日期:1994-01-01 00:00:00
abstract::SHetA2 is a small molecule flexible heteroarotinoid (Flex-Het) with promising cancer prevention and therapeutic activity. Extensive preclinical testing documented lack of SHetA2 toxicity at doses 25 to 150 fold above effective doses. Knowledge of the SHetA2 molecular target(s) that mediate(s) the mechanism of SHetA2 a...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-013-0041-x
更新日期:2014-06-01 00:00:00
abstract::We studied the effect of riccardin D, a macrocyclic bisbibenzyl, which was isolated from the Chinese liverwort plant, on human leukemia cells and the underlying molecular mechanism. Riccardin D had a significant antiproliferative effect on human leukemia cell lines HL-60, K562 and its multidrug resistant (MDR) counter...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9554-8
更新日期:2012-02-01 00:00:00
abstract:PURPOSE:To assess the maximum well-tolerated dose (MWTD), dose limiting toxicity (DLT), pharmacokinetics (PK) and pharmacodynamics of zibotentan, a novel specific endothelin-A receptor antagonist, in patients with metastatic prostate cancer. METHODS:Patients with metastatic, castrate-resistant prostate cancer (CRPC) w...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-009-9318-5
更新日期:2011-02-01 00:00:00
abstract:OBJECTIVE:Everolimus (RAD001) is a novel mammalian target of rapamycin (mTOR) inhibitor, and anti-proliferative activity in various malignancies has been reported. This study evaluated the anti-tumor effects and schedule-dependent synergism of everolimus in combination with other chemotherapeutic agents in T-cell lymph...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9558-4
更新日期:2012-02-01 00:00:00
abstract::Fifteen patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck received a 5 day continuous I.V. infusion of 6-thioguanine repeated every five weeks. Dose limiting toxicity was primarily hematological with grade III/IV leucopenia and thrombocytopenia seen in seven patients. Nausea and vo...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00873122
更新日期:1992-07-01 00:00:00
abstract::Background DR5 is a transmembrane receptor that transduces extracellular ligand-binding to activate apoptosis signaling cascades. This phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of a new monoclonal antibody potent DR5 agonist, DS-8273a, in subjects with advanced solid...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-016-0420-1
更新日期:2017-06-01 00:00:00
abstract::Transforming growth factor-beta (TGF-β) signaling pathway plays pivotal roles in various types of cancer. TGF-β receptor 2 (TGFβR2) contains a kinase domain that phosphorylates and activates the downstream of the TGF-β signaling pathway. Our previous microarray analysis revealed marked changes in miR-181a expression i...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-018-0695-5
更新日期:2019-10-01 00:00:00
abstract::Colon cancer is the third most malignant neoplasm in the world and it remains today an important cause of death, especially in western countries. In this study, we have evaluated the chemopreventive efficacy of morin on tissue lipid peroxidation and antioxidant status, which are used as biomarkers in 1,2-dimethylhydra...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9136-1
更新日期:2009-02-01 00:00:00
abstract::Background Preclinical evidence has suggested that a subset of pancreatic cancers with the G12R mutational isoform of the KRAS oncogene is more sensitive to MAPK pathway blockade than pancreatic tumors with other KRAS isoforms. We conducted a biomarker-driven trial of selumetinib (KOSELUGO™; ARRY-142886), an orally ac...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-01044-8
更新日期:2021-01-06 00:00:00
abstract::Posterior reversible encephalopathy syndrome (PRES) is a clinical/radiological syndrome characterized by symptoms that can include seizure, headache, impaired vision and hypertension, and can be confirmed by magnetic resonance imaging. Numerous reports have emerged that describe PRES in cancer patients. The list of me...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-014-0193-3
更新日期:2015-06-01 00:00:00
abstract::A retrospective cohort study was performed to investigate the effectiveness of preemptive postsurgical therapy with cetuximab for patients with a major risk of recurrence or metastasis after clinical complete resection of primary oral squamous cell carcinoma (OSCC). The study period was from 2007 to 2019 for patients ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-021-01062-0
更新日期:2021-01-15 00:00:00
abstract:BACKGROUND:Docetaxel-prednisone (DP) is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC). Orteronel (TAK-700) is an investigational, selective, non-steroidal inhibitor of 17,20-lyase, a key enzyme in androgenic hormone production. This phase 1/2 study evaluated orteronel plus DP in mCRPC ...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-014-0199-x
更新日期:2015-04-01 00:00:00
abstract::We have developed a specific and sensitive method aiming at docetaxel (Taxotere) determination in plasma of treated patients. This involved solid-phase extraction of 1 ml of plasma onto carboxylic acid (CBA) grafted silica cartridges followed by reversed-phase liquid chromatography with UV detection. The best selectiv...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/a:1006327302041
更新日期:1999-01-01 00:00:00
abstract::We previously found that the novel histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) had greater selectivity against cutaneous T-cell lymphoma (CTCL) than SAHA. AN-7 synergizes with doxorubicin (Dox), an anthracycline antibiotic that induces DNA breaks. This study aimed to elucidate the m...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0500-x
更新日期:2018-02-01 00:00:00
abstract::Breast cancer is commonly treated with anti-estrogens or aromatase inhibitors, but resistant disease eventually develops and new therapies for such resistance are of great interest. We have previously isolated several tamoxifen-resistant variant sub-lines of the MCF-7 breast cancer cell line and provided evidence that...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9768-4
更新日期:2012-12-01 00:00:00