Cellular pharmacology of fluorinated pyrimidines in vivo in man.

abstract：:The discovery of multiple putative therapeutic targets and multiple putative agents for these targets in prostate cancer in the coming years poses significant challenges for clinical trial design. This is especially true for cytostatic agents that are not expected to lead to frank tumor shrinkage or declines in the PS...

journal_title：Investigational new drugs

authors： Stadler W

更新日期：2002-05-01 00:00:00

abstract：PURPOSE:Combining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested uti...

journal_title：Investigational new drugs

authors： Millward M,Price T,Townsend A,Sweeney C,Spencer A,Sukumaran S,Longenecker A,Lee L,Lay A,Sharma G,Gemmill RM,Drabkin HA,Lloyd GK,Neuteboom ST,McConkey DJ,Palladino MA,Spear MA

更新日期：2012-12-01 00:00:00

abstract：:Tyrosine kinase inhibitors (TKI) or monoclonal antibodies targeting EGFR, HER2 or VEGFR receptors have demonstrated substantial clinical benefit in patients with advanced breast cancer, colon cancer, head and neck cancer, non-small cell lung cancer, and renal cell carcinoma. Nevertheless, these drugs have some target ...

journal_title：Investigational new drugs

authors： Bahleda R,Massard C,Soria JC,Izzedine H,Cohen A,Ederhy S

更新日期：2010-06-01 00:00:00

abstract：:Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellula...

journal_title：Investigational new drugs

authors： Dredge K,Hammond E,Davis K,Li CP,Liu L,Johnstone K,Handley P,Wimmer N,Gonda TJ,Gautam A,Ferro V,Bytheway I

更新日期：2010-06-01 00:00:00

abstract：BACKGROUND:Therapeutic approaches to marginal zone B-cell lymphoma (MZL) continue to evolve. Localized MZL responds favorably to local treatments, including surgery and/or local radiation therapy. However, MZL manifests as a disseminated disease in one-third of the cases at diagnosis. Moreover, relapses involving dista...

journal_title：Investigational new drugs

authors： Oh SY,Kim WS,Lee DH,Kim SJ,Kim SH,Ryoo BY,Kang HJ,Choi YJ,Chung JS,Kim HJ,Suh C

更新日期：2010-04-01 00:00:00

abstract：:Based on the high response rates seen among patients with colon cancer receiving high dose Melphalan with autologous marrow infusion, the Southwest Oncology Group conducted a Phase II trial of the compound at a conventional dose. The initial starting dose of 40 mg/m2 was reduced to 30 mg/m2 after severe myelotoxicity ...

journal_title：Investigational new drugs

authors： Knight WA 3rd,Goodman P,Taylor SA,Macdonald JS,Coltman CA Jr,Constanzi JJ,Baker LH

更新日期：1990-01-01 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

authors： Bujak E,Pretto F,Neri D

更新日期：2015-08-01 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：PURPOSE:To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and tolerability of MN-209, a novel vascular disrupting agent, in patients with advanced solid tumors. STUDY DESIGN:MN-029 was administered weekly for three consecutive weeks out of four; two cycles were planned. Dose escalation ...

journal_title：Investigational new drugs

authors： Traynor AM,Gordon MS,Alberti D,Mendelson DS,Munsey MS,Wilding G,Gammans RE,Read WL

更新日期：2010-08-01 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

authors： Moyal L,Goldfeiz N,Gorovitz B,Rephaeli A,Tal E,Tarasenko N,Nudelman A,Ziv Y,Hodak E

更新日期：2018-02-01 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

authors： Broekman KE,Hof MAJ,Touw DJ,Gietema JA,Nijman HW,Lefrandt JD,Reyners AKL,Jalving M

更新日期：2020-10-01 00:00:00

abstract：:Introduction In preclinical data, the combination therapy with S-1 and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) had a synergistic antitumor effect on non-small cell lung cancer (NSCLC), regardless of the EGFR mutation status. Patients and Methods Patients with previously treated NSCLC an...

journal_title：Investigational new drugs

authors： Nakahara Y,Shimokawa T,Misumi Y,Nogami N,Shinkai T,Seki N,Hosomi Y,Hida N,Okamoto H

更新日期：2020-08-15 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

authors： Hoyt MT,Palchaudhuri R,Hergenrother PJ

更新日期：2011-08-01 00:00:00

abstract：:Didemnin B is a depsipeptide derived from a Caribbean tunicate (sea squirt) that has demonstrated antineoplastic activity against a variety of murine tumor models, including the L1210 and P388 leukemia, the B16 melanoma, and M5076 sarcoma cell lines. Based on these data, we designed a phase II trial in which 15 patien...

journal_title：Investigational new drugs

authors： Jones DV Jr,Ajani JA,Blackburn R,Daugherty K,Levin B,Patt YZ,Abbruzzese JL

更新日期：1992-08-01 00:00:00

abstract：:This study was conducted to assess the efficacy and toxicity of suramin administered using a fixed dose schedule in patients with advanced renal cell carcinoma. Fourteen eligible patients with advanced renal cell carcinoma were enrolled and treated on a fixed dose schedule of suramin administered over 12 weeks. Surami...

journal_title：Investigational new drugs

authors： Dreicer R,Smith DC,Williams RD,See WA

更新日期：1999-01-01 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

abstract：:Virotherapy is an emerging strategy for the treatment of cancer that utilizes both replication-competent and genetically modified viruses to selectively kill tumor cells. We have previously shown that Coxsackievirus A21 (CVA21), a common-cold producing enterovirus, is an effective oncolytic agent against human melanom...

journal_title：Investigational new drugs

authors： Skelding KA,Barry RD,Shafren DR

更新日期：2012-04-01 00:00:00

abstract：:LY2457546 is a potent and orally bioavailable inhibitor of multiple receptor tyrosine kinases involved in angiogenic and tumorigenic signalling. In biochemical and cellular assays, LY2457546 demonstrates potent activity against targets that include VEGFR2 (KDR), PDGFRβ, FLT-3, Tie-2 and members of the Eph family of re...

journal_title：Investigational new drugs

authors： Burkholder TP,Clayton JR,Rempala ME,Henry JR,Knobeloch JM,Mendel D,McLean JA,Hao Y,Barda DA,Considine EL,Uhlik MT,Chen Y,Ma L,Bloem LJ,Akunda JK,McCann DJ,Sanchez-Felix M,Clawson DK,Lahn MM,Starling JJ

更新日期：2012-06-01 00:00:00

abstract：:Fifty-four evaluable patients with SCLC previously treated with chemotherapy received either N-methylformamide or spirogermanium. There was one partial response to N-methylformamide. The median survival times for patients treated with N-MF and spirogermanium were 11.7 and 12.6 weeks respectively. Five patients treated...

journal_title：Investigational new drugs

authors： Ettinger DS,Finkelstein DM,Abeloff MD,Chang YC,Smith TJ,Oken MM,Ruckdeschel JC

更新日期：1990-05-01 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

authors： Ge S,Zhang H,Deng T,Sun W,Ning T,Fan Q,Wang Y,Wang X,Zhang Q,Zhou Z,Yang H,Ying G,Ba Y

更新日期：2019-10-01 00:00:00

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

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

更新日期：2010-02-01 00:00:00

abstract：:Herein we describe a series of multifunctional 5-aminolevulinic-acid (ALA) prodrugs for photodynamic dependent and independent cancer therapy (PDT). We studied the cell-death mechanisms in glioblastoma U251 cells treated with four ALA-prodrugs: (1) AlaAcBu, that releases ALA, acetaldehyde, and butyric acid; (2) AlaFaB...

journal_title：Investigational new drugs

authors： Berkovitch-Luria G,Weitman M,Nudelman A,Rephaeli A,Malik Z

更新日期：2012-06-01 00:00:00

abstract：:The limiting toxicity of low dose continuous infusion 5-fluorouracil (200-300 mg/m2/day) is often palmar-plantar erythrodysesthesia (PPE). PPE developed in 16/25 patients (exact 95% confidence interval of 42%-82%) with metastatic colon cancer enrolled in a phase II trial. In this trial, 5-FU was given continuously at ...

journal_title：Investigational new drugs

authors： Fabian CJ,Molina R,Slavik M,Dahlberg S,Giri S,Stephens R

更新日期：1990-02-01 00:00:00

abstract：INTRODUCTION:For decades, determination of the recommended Phase 2 dose (RP2D) was based on the toxicity (especially the maximum tolerated dose or MTD) experienced by patients enrolled in dose-escalating Phase 1 trials investigating anti-cancer agents. Recent studies suggest that this toxicity-based strategy is not sui...

journal_title：Investigational new drugs

authors： Penel N,Duhamel A,Adenis A,Devos P,Isambert N,Clisant S,Bonneterre J

更新日期：2012-04-01 00:00:00

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

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

abstract：:The poor prognosis of children with high-grade glioma (HGG) and high-risk neuroblastoma, despite multidisciplinary therapeutic approaches, demands new treatments for these indications. F14512 is a topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells via the Polyamine...

journal_title：Investigational new drugs

authors： Leblond P,Boulet E,Bal-Mahieu C,Pillon A,Kruczynski A,Guilbaud N,Bailly C,Sarrazin T,Lartigau E,Lansiaux A,Meignan S

更新日期：2014-10-01 00:00:00

abstract：:Signal transduction pathways, which regulate cell growth and survival, are up-regulated in many cancers and there is considerable interest in their pharmaceutical modulation for cancer treatment. However inhibitors of single pathway components induce feedback mechanisms that overcome the growth moderating effect of th...

journal_title：Investigational new drugs

authors： Phyu SM,Smith TAD

更新日期：2019-06-01 00:00:00

abstract：:Background The MAPK pathway plays a central role in regulation of several cellular processes, and its dysregulation is a hallmark of biliary tract cancer (BTC). Binimetinib (MEK162), a potent, selective oral MEK1/2 inhibitor, was assessed in patients with advanced BTC. Patients and Methods An expansion cohort study in...

journal_title：Investigational new drugs

authors： Finn RS,Ahn DH,Javle MM,Tan BR Jr,Weekes CD,Bendell JC,Patnaik A,Khan GN,Laheru D,Chavira R,Christy-Bittel J,Barrett E,Sawyer MB,Bekaii-Saab TS

更新日期：2018-12-01 00:00:00

abstract：:AZQ was given intravenously to 23 patients with mixed mesodermal sarcoma of the uterus refractory to conventional treatment at a dose of 22.5-30 mg/m2 q three weeks. There was one partial response lasting seven weeks and one drug-related death. Based upon the activity observed in this trial, there does not appear to b...

journal_title：Investigational new drugs

authors： Slayton RE,Blessing JA,Clarke-Pearson D

更新日期：1991-02-01 00:00:00

abstract：:Coptis chinensis Franch. has been extensively used in traditional Chinese medicine. The chemical structure of oxyepiberberine, as an alkaloid isolated from Coptis chinensis Franch., has been previously studied. However, anti-cancer effects and underlying mechanisms of oxyepiberberine need to be explored. This study ai...

journal_title：Investigational new drugs

authors： Ning H,Lu W,Jia Q,Wang J,Yao T,Lv S,Li Y,Wen H

更新日期：2020-09-30 00:00:00