Capecitabine: preclinical pharmacology studies.

abstract：:XK-469 is advancing to Phase I clinical trials. Preclinical studies were carried out to assist in clinical applications. DOSE-SCHEDULE ROUTE TESTING: Single dose i.v. treatment with XK-469 produced lethality (LD20 to LD100) above 142 mg/kg. Optimum treatment required total dosages of 350 to 600 mg/kg. Furthermore, hig...

journal_title：Investigational new drugs

authors： Polin L,White K,Kushner J,Paluch J,Simpson C,Pugh S,Edelstein MK,Hazeldine S,Fontana J,LoRusso P,Horwitz JP,Corbett TH

更新日期：2002-02-01 00:00:00

abstract：BACKGROUND:Foretinib is a small-molecule, oral multikinase inhibitor primarily targeting the mesenchymal epithelial transition (MET) factor receptor, and the vascular endothelial growth factor receptor 2. We conducted a phase II study to evaluate the single-agent activity and tolerability of foretinib in patients with ...

journal_title：Investigational new drugs

authors： Seiwert T,Sarantopoulos J,Kallender H,McCallum S,Keer HN,Blumenschein G Jr

更新日期：2013-04-01 00:00:00

abstract：:Taxol was administered as a 24-hour continuous infusion at 250 mg/m2 in this Phase II trial in patients with adenocarcinomas of the upper gastrointestinal tract (UGIT). Twenty-five patients were entered between July 1991 and June 1992, twenty-three were eligible and were evaluated for toxicity and twenty-two were asse...

journal_title：Investigational new drugs

authors： Einzig AI,Lipsitz S,Wiernik PH,Benson AB 3rd

更新日期：1995-01-01 00:00:00

abstract：BACKGROUND:Lactoferrin is an iron-binding glycoprotein first identified in breast milk as a protein product of mammary epithelial cells. Its immunomodulatory functions include activation of NK and lymphokine-activated killer cells and enhancement of PMN and macrophage cytotoxicity. Studies in animal models have shown p...

journal_title：Investigational new drugs

authors： Hayes TG,Falchook GF,Varadhachary GR,Smith DP,Davis LD,Dhingra HM,Hayes BP,Varadhachary A

更新日期：2006-05-01 00:00:00

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

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

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

authors： Steube KG,Grunicke D,Drexler HG

更新日期：1994-01-01 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

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

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

authors： Yamamoto Y,Okamoto I,Otsubo K,Iwama E,Hamada N,Harada T,Takayama K,Nakanishi Y

更新日期：2015-10-01 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

authors： Whittle SB,Patel K,Zhang L,Woodfield SE,Du M,Smith V,Zage PE

更新日期：2016-12-01 00:00:00

abstract：AIM:5,6-Dimethylxanthenone-4-acetic acid (DMXAA) (ASA404), a low molecular weight antivascular drug currently in clinical trial, acts both directly on the tumour vascular endothelium and indirectly through the induction of inflammatory cytokines and other vasoactive molecules from macrophages and other host cells. We w...

journal_title：Investigational new drugs

authors： Wang LC,Ching LM,Paxton JW,Kestell P,Sutherland R,Zhuang L,Baguley BC

更新日期：2009-06-01 00:00:00

abstract：:We explored whether barasertib (AZD1152), a selective Aurora B kinase inhibitor, is a substrate for P-glycoprotein (Pgp, MDR1), breast cancer resistance protein (BCRP), and multidrug resistance protein 2 (MRP2) in vitro. Cell survival, drug transport, and competition experiments with barasertib pro-drug and the more a...

journal_title：Investigational new drugs

authors： Marchetti S,Pluim D,van Eijndhoven M,van Tellingen O,Mazzanti R,Beijnen JH,Schellens JH

更新日期：2013-10-01 00:00:00

abstract：BACKGROUND:To analyze the feasibility of capecitabine with weekly irinotecan and concurrent radiotherapy followed by laparoscopic-total mesorectal excision (LTME) in rectal cancer patients. METHODS:Eligible criteria included adenocarcinoma of the rectum staged by endoscopic ultrasonography (u), spiral abdominal and pe...

journal_title：Investigational new drugs

authors： Ugidos L,Delgado S,Conill C,Ginés A,Gallego R,Ayuso JR,Miquel R,Tosca M,de Lacy A,Castells A,Maurel J

更新日期：2009-06-01 00:00:00

abstract：:Over forty papers describing correlations between in vitro human tumor sensitivity to a variety of chemotherapeutic agents and the in vivo response of patients to those agents have been published since the publication in 1978 by Salmon and Hamburger of their results of a human tumor colony-forming chemosensitivity ass...

journal_title：Investigational new drugs

authors： Bradley EC,Issell BF,Hellman R

更新日期：1984-01-01 00:00:00

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

authors： Oka S,Ono K,Nohgawa M

更新日期：2020-10-01 00:00:00

abstract：:CP-4126 is a gemcitabine (2',2'-difluorodeoxycytidine; dFdC) 5' elaidic acid ester. The purpose of this dose-escalating study was to assess safety, pharmacokinetics (PK) and preliminary antitumor activity of the oral formulation and to determine the recommended dose (RD) for phase II studies. The study had a two-step ...

journal_title：Investigational new drugs

authors： Stuurman FE,Voest EE,Awada A,Witteveen PO,Bergeland T,Hals PA,Rasch W,Schellens JH,Hendlisz A

更新日期：2013-08-01 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

authors： Kaplan A,Benkli K,Koparal AT

更新日期：2018-10-01 00:00:00

abstract：:Aberrant activation of the Wnt/β-catenin signaling pathway promotes osteosarcoma tumorigenesis and metastasis. In this study, we tested the hypothesis that osteosarcoma progression may be delayed by disrupting the Wnt/β-catenin pathway using small molecule inhibitors such as curcumin and PKF118-310. Effective inhibiti...

journal_title：Investigational new drugs

authors： Leow PC,Tian Q,Ong ZY,Yang Z,Ee PL

更新日期：2010-12-01 00:00:00

abstract：:There is no effective systemic therapy for disseminated metastatic melanoma. Data suggest that endothelin may play a role in pathophysiology of melanoma and that the dual endothelin receptor antagonist bosentan may have anti-tumor activity. This multicenter, open-label, single-arm, prospective, proof-of-concept study ...

journal_title：Investigational new drugs

authors： Kefford R,Beith JM,Van Hazel GA,Millward M,Trotter JM,Wyld DK,Kusic R,Shreeniwas R,Morganti A,Ballmer A,Segal E,Nayler O,Clozel M

更新日期：2007-06-01 00:00:00

abstract：:3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or g...

journal_title：Investigational new drugs

authors： Margolin K,Doroshow J,Leong L,Akman S,Carr B,Odujinrin O,Flanagan B,Grove W,DeLap R,Goldberg D

更新日期：1990-11-01 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

authors： Ardiet CJ,Tranchand B,Zanetta S,Guillot A,Bernard E,Peguy M,Rebattu P,Droz JP

更新日期：1999-01-01 00:00:00

abstract：:Fifteen patients with advanced, cisplatin-refractory germ cell tumors (GCT) were treated with iproplatin (CHIP). No objective responses were noted in any of the patients treated. By restricting the entry criteria to heavily pre-treated patients, the identification of new active agents in phase II trials may be hindere...

journal_title：Investigational new drugs

authors： Murphy BA,Motzer RJ,Bosl GJ

更新日期：1992-11-01 00:00:00

abstract：:Fourteen patients with active chronic lymphocytic leukemia who had failed prior therapy were treated with progressive doses of weekly intravenous colchicine beginning at 2 mg and escalating as high as 7 mg in a single injection. Responses were seen in two of 14, with a lessening of adenopathy and splenomegaly. Toxicit...

journal_title：Investigational new drugs

authors： Weick JK,Livingston RB,Van Slyck EJ

更新日期：1983-01-01 00:00:00

abstract：:VEGF signaling through VEGFR-2 is the major factor in glioblastoma angiogenesis. CT-322, a pegylated protein engineered from the 10th type III human fibronectin domain, binds the VEGFR-2 extracellular domain with high specificity and affinity to block VEGF-induced VEGFR-2 signaling. This study evaluated CT-322 in an o...

journal_title：Investigational new drugs

authors： Schiff D,Kesari S,de Groot J,Mikkelsen T,Drappatz J,Coyle T,Fichtel L,Silver B,Walters I,Reardon D

更新日期：2015-02-01 00:00:00

abstract：:Myricetin is a naturally omnipresent benzo-α-pyrone flavonoids derivative; has potent anticancer activity. Receptor tyrosine kinases family provides the decisive role in cancer initiation and progression. These receptors have recently caught the attention of the researchers as an attractive target to combat cancer, ow...

journal_title：Investigational new drugs

authors： Singh P,Bast F

更新日期：2015-06-01 00:00:00

abstract：PURPOSE:Vorinostat (V) at levels >2.5 µM enhances chemotherapy in vitro. Yet the approved oral dose of 400 mg inconsistently achieves this level in patients. We developed an intermittent oral pulse-dose schedule of V to increase serum levels. We combined V with the cyclin dependent kinase inhibitor flavopiridol (F) whi...

journal_title：Investigational new drugs

authors： Dickson MA,Rathkopf DE,Carvajal RD,Grant S,Roberts JD,Reid JM,Ames MM,McGovern RM,Lefkowitz RA,Gonen M,Cane LM,Dials HJ,Schwartz GK

更新日期：2011-10-01 00:00:00

abstract：:Gemcitabine is a nucleoside analogue with excellent clinical activity against solid tumors. Within the cell, gemcitabine is rapidly phosphorylated to its active di- and triphosphate metabolites. Cytotoxicity with gemcitabine appears to be related to multiple effects on DNA replication, where gemcitabine triphosphate c...

journal_title：Investigational new drugs

authors： Shewach DS,Lawrence TS

更新日期：1996-01-01 00:00:00

abstract：BACKGROUND:Dacomitinib (PF-00299804) is an oral, irreversible, small molecule inhibitor of human epidermal growth factor receptor-1, -2, and -4 tyrosine kinases. METHODS:This phase I, open-label, dose-escalation study (clinicaltrials.gov: NCT00783328) primarily evaluated the safety and tolerability of dacomitinib by d...

journal_title：Investigational new drugs

authors： Takahashi T,Boku N,Murakami H,Naito T,Tsuya A,Nakamura Y,Ono A,Machida N,Yamazaki K,Watanabe J,Ruiz-Garcia A,Imai K,Ohki E,Yamamoto N

更新日期：2012-12-01 00:00:00

abstract：:Seventeen patients with small cell lung cancer entered a phase II trial testing the feasibility of adding high dose epirubicin (100-120 mg/m2, day 1) in combination with etoposide (60-80 mg/m2, days 1-5) and cisplatin (70 mg/m2, day 1) courses repeated every three weeks. Complete responders received thoracic (40 Gy) a...

journal_title：Investigational new drugs

authors： Rosell R,Carles J,Abad A,Jimeno JM,Moreno I,Barnadas A,Ribelles N,Haboubi N

更新日期：1992-07-01 00:00:00

abstract：:Castrate-Resistant Prostate-Cancer (CRPC) is one of the most common malignancies occurring in men. Unfortunately, even if several recently approved agents clinically improved the outcome of CRPC patients, none of these is curative especially for a splice version of the Androgen Receptor (AR) AR-V7, which is a variant ...

journal_title：Investigational new drugs

authors： Sobhani N,Generali D,D'Angelo A,Aieta M,Roviello G

更新日期：2018-12-01 00:00:00

abstract：:An HPLC analytical method was applied to the determination of plasma concentrations of 5,6-dihydro-5-azacytidine (NSC 264880, DHAC) in two foxhounds after a rapid intravenous infusion of 300 mg/kg DHAC. The dose employed is the mouse equivalent LD10 dose which results in mild reversible toxicity in the dog. The declin...

journal_title：Investigational new drugs

authors： Malspeis L,Cheng H,Staubus AE

更新日期：1983-01-01 00:00:00