Phase I dose-finding and pharmacokinetic trial of orally administered indibulin (D-24851) to patients with solid tumors.

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

authors： Petrylak DP,Gandhi JG,Clark WR,Heath E,Lin J,Oh WK,Agus DB,Carthon B,Moran S,Kong N,Suri A,Bargfrede M,Liu G

更新日期：2015-04-01 00:00:00

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

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

abstract：:Artemisinin and its derivatives are well known antimalarial drugs, particularly useful after resistance to traditional antimalarial pharmaceuticals has started to occur in Plasmodium falciparum. In recent years, anticancer activity of artemisinin has been reported both in vitro and in vivo. Artemisinin has inhibitory ...

journal_title：Investigational new drugs

authors： Buommino E,Baroni A,Canozo N,Petrazzuolo M,Nicoletti R,Vozza A,Tufano MA

更新日期：2009-10-01 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

authors： Xue X,Qu XJ,Gao ZH,Sun CC,Liu HP,Zhao CR,Cheng YN,Lou HX

更新日期：2012-02-01 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：:The matrix metalloproteinases (MMPs) are a family of at least fifteen secreted and membrane-bound zinc-endopeptidases. Collectively, these enzymes can degrade all of the components of the extracellular matrix, including fibrallar and non-fibrallar collagens, fibronectin, laminin and basement membrane glycoproteins. MM...

journal_title：Investigational new drugs

authors： Wojtowicz-Praga SM,Dickson RB,Hawkins MJ

更新日期：1997-01-01 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

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

更新日期：1996-01-01 00:00:00

abstract：:Pancreatic cancer is a lethal disease characterized by local invasion and early dissemination. It is resistant to conventional surgical, radiotherapeutic, and chemotherapeutic modalities. These interventions have had minimal impact on overall survival with very few patients enjoying long term survival. Over the past f...

journal_title：Investigational new drugs

authors： Wolff RA,Chiao P,Lenzi R,Pisters PW,Lee JE,Janjan NA,Crane CH,Evans DB,Abbruzzese JL

更新日期：2000-02-01 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

authors： Lopez M,Di Lauro L,Papaldo P,Lazzaro B,Ganzina F,Di Pietro N

更新日期：1986-01-01 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：: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：:Diflubenzuron (DFB) and Clanfenur (CFN) belong to a group of compounds called Benzoylphenyl Ureas (BPUs). Several BPUs regulate cell growth in insects and/or inhibit growth of B-16 murine melanomas. In view of potential clinical use for these compounds, DFB and CFN were selected as examples of BPUs and tested for effe...

journal_title：Investigational new drugs

authors： Jenkins VK,Juneja HS,Ives K,Lee S,Perry RR

更新日期：1993-11-01 00:00:00

abstract：BACKGROUND:Gemcitabine is a pro-drug that has to be phosphorylated to gemcitabine-triphosphate in order to exhibit its antineoplastic activity. This reaction involves the enzyme deoxycytidine kinase which is saturated at plasma concentrations following standard 30-min infusions. Pharmacological studies indicate that pr...

journal_title：Investigational new drugs

authors： Schmid P,Schweigert M,Beinert T,Flath B,Sezer O,Possinger K

更新日期：2005-03-01 00:00:00

abstract：:Fifteen patients with advanced carcinoma of the breast who had failed prior chemotherapy, were treated with recombinant gamma interferon at a dose of 2mg/m2 (1mg = 2.4 X 10(7) international units) intravenously for five consecutive days every other week. The median patient age was 51 and all patients had a performance...

journal_title：Investigational new drugs

authors： Muss HB,Caponera M,Zekan PJ,Jackson DV Jr,Stuart JJ,Richards F,Cooper MR,Levin EA,Reich SD,Capizzi RL

更新日期：1986-01-01 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

authors： Saydjari R,Townsend CM Jr,Barranco SC,Thompson JC

更新日期：1987-01-01 00:00:00

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

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

更新日期：2013-02-01 00:00:00

abstract：BACKGROUND:To explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology. METHODS:Patients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study of lapatinib 1,500 mg PO daily....

journal_title：Investigational new drugs

authors： Galsky MD,Von Hoff DD,Neubauer M,Anderson T,Fleming M,Nagarwala Y,Mahoney JM,Midwinter D,Vocila L,Zaks TZ

更新日期：2012-04-01 00:00:00

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

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

abstract：BACKGROUND:This Phase-I-study aimed to determine the recommended Phase-II-dosing-schedule of LY2334737, an oral gemcitabine prodrug, in patients with advanced/metastatic solid tumors. Pharmacokinetics, cytokeratin-18 (CK18) levels, genetic polymorphisms, and antitumor activity were additionally evaluated. METHODS:Pati...

journal_title：Investigational new drugs

authors： Faivre SJ,Olszanski AJ,Weigang-Köhler K,Riess H,Cohen RB,Wang X,Myrand SP,Wickremsinhe ER,Horn CL,Ouyang H,Callies S,Benhadji KA,Raymond E

更新日期：2015-12-01 00:00:00

abstract：:Acquired resistance to tamoxifen (Tam) is a critical problem in breast cancer therapy. Therefore, new potential strategies for Tam-resistant breast cancer are needed recently. In this study, we synthesized a novel histone deacetylase (HDAC) inhibitor, MHY218, for the development of potent inhibitors of HDAC and evalua...

journal_title：Investigational new drugs

authors： Park JH,Ahn MY,Kim TH,Yoon S,Kang KW,Lee J,Moon HR,Jung JH,Chung HY,Kim HS

更新日期：2012-10-01 00:00:00

abstract：:We have previously shown that the insulinotropic imidazoline compound RX871024 induces death of insulinoma MIN6 cells, an effect involving stimulation of c-Jun N-terminal kinase (JNK) and caspase 3. It has also been reported that AMP-activated protein kinase (AMPK) activates JNK and induces β-cell death. Here we show ...

journal_title：Investigational new drugs

authors： Zaitseva II,Zaitsev SV,Berggren PO

更新日期：2016-08-01 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：: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：: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

authors： Denis LJ,Verweij J

更新日期：1997-01-01 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：:Studies with CGP 41 251 (I), an N-benzoylstaurosporine derivative and PKC-alpha inhibitor, revealed that oral administration of 400 microg/day of the compound to wild type mice on four successive days reversed multi drug resistance (Killion et al. Oncology Research 7: 453-459, 1995). In our study, the same regimen of ...

journal_title：Investigational new drugs

authors： van Gijn R,van Tellingen O,Haverkate E,Kettenes-van den Bosch JJ,Bult A,Beijnen JH

更新日期：1999-01-01 00:00:00

abstract：INTRODUCTION:Heat shock protein 90 (Hsp90) has been studied as a therapeutic target in many cancers. In preclinical trials, the Hsp90 ATPase inhibitor ganetespib demonstrated potent inhibition of solid tumor growth, with superior potency than prior Hsp90 inhibitors. Given the promising preclinical outcome and favorable...

journal_title：Investigational new drugs

authors： Thakur MK,Heilbrun LK,Sheng S,Stein M,Liu G,Antonarakis ES,Vaishampayan U,Dzinic SH,Li X,Freeman S,Smith D,Heath EI

更新日期：2016-02-01 00:00:00

abstract：:Background This open-label, first-in-human, phase 1 study evaluated AMG 232, an oral selective MDM2 inhibitor in patients with TP53 wild-type (P53WT), advanced solid tumors or multiple myeloma (MM). Methods In the dose escalation (n = 39), patients with P53WT refractory solid tumors enrolled to receive once-daily AMG ...

journal_title：Investigational new drugs

authors： Gluck WL,Gounder MM,Frank R,Eskens F,Blay JY,Cassier PA,Soria JC,Chawla S,de Weger V,Wagner AJ,Siegel D,De Vos F,Rasmussen E,Henary HA

更新日期：2020-06-01 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

authors： Hazawa M,Takahashi K,Wada K,Mori T,Kawahara N,Kashiwakura I

更新日期：2011-02-01 00:00:00

abstract：:Gemcitabine is a deoxycytidine (dCyd) analog with activity in leukemia and solid tumors, which requires phosphorylation by deoxycytidine kinase (dCK). Decreased membrane transport is a mechanism of resistance to gemcitabine. In order to facilitate gemcitabine uptake and prolong retention in the cell, a lipophilic pro-...

journal_title：Investigational new drugs

authors： Bergman AM,Adema AD,Balzarini J,Bruheim S,Fichtner I,Noordhuis P,Fodstad O,Myhren F,Sandvold ML,Hendriks HR,Peters GJ

更新日期：2011-06-01 00:00:00