abstract：:Bombesin/gastrin-releasing peptides (BN/GRP) were shown to bind selectively to cell surface receptors, stimulating the growth of various types of malignancies in murine and human models. The novel BN/GRP synthetic receptor antagonist, RC-3095, was able to produce long-lasting tumor regressions in murine and human tumo...

journal_title：Investigational new drugs

authors： Schwartsmann G,DiLeone LP,Horowitz M,Schunemann D,Cancella A,Pereira AS,Richter M,Souza F,da Rocha AB,Souza FH,Pohlmann P,De Nucci G

更新日期：2006-09-01 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：PURPOSE:To evaluate the impact of flutamide on survival of patients with unresectable pancreatic cancer. METHODS:This single institution, randomized, double-blind, placebo controlled study compared flutamide in the dose of 250 mg three times daily (n = 23) versus placebo (n = 23) in patients with histologically proven...

journal_title：Investigational new drugs

authors： Negi SS,Agarwal A,Chaudhary A

更新日期：2006-05-01 00:00:00

abstract：PURPOSE:Amrubicin is a novel 9-aminoanthracycline. This multicenter phase II study was conducted to evaluate the efficacy and safety of amrubicin in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:Sixty-one previously untreated patients with stage III or IV NSCLC were entered this study. The pat...

journal_title：Investigational new drugs

authors： Sawa T,Yana T,Takada M,Sugiura T,Kudoh S,Kamei T,Isobe T,Yamamoto H,Yokota S,Katakami N,Tohda Y,Kawakami A,Nakanishi Y,Ariyoshi Y

更新日期：2006-03-01 00:00:00

abstract：:TNF-alpha may improve drug delivery to tumors by alteration of vascular permeability. However, toxicity precludes its systemic administration in patients. NGR-TNF comprises TNF coupled to the peptide CNGRC, which is a ligand for CD13. CD13 is expressed on tumor vasculature. Therefore, to assess the efficacy of NGR-TNF...

journal_title：Investigational new drugs

authors： van Laarhoven HW,Gambarota G,Heerschap A,Lok J,Verhagen I,Corti A,Toma S,Gallo Stampino C,van der Kogel A,Punt CJ

更新日期：2006-01-01 00:00:00

abstract：:Ninety per cent of pancreatic adenocarcinomas (PC) contain mutations of the K-Ras proto-oncogene resulting in constitutively activated Ras protein. A critical step in Ras activation is farnesylation of Ras protein. Farnesyl transferase inhibitors are compounds that inhibit farnesylation. We report the results of a pha...

journal_title：Investigational new drugs

authors： Macdonald JS,McCoy S,Whitehead RP,Iqbal S,Wade JL 3rd,Giguere JK,Abbruzzese JL

更新日期：2005-10-01 00:00:00

abstract：BACKGROUND:ONT-093 is an orally bioavailable inhibitor of P-glycoprotein (P-gp). In pre-clinical studies, ONT-093 could inhibit P-gp and reverse multidrug resistance at nM concentrations with no effect on paclitaxel pharmacokinetics. Phase I trials of ONT-093 in normal human volunteers showed no dose-limiting toxicitie...

journal_title：Investigational new drugs

authors： Chi KN,Chia SK,Dixon R,Newman MJ,Wacher VJ,Sikic B,Gelmon KA

更新日期：2005-08-01 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：BACKGROUND:The primary objective of this Phase I study was to determine the maximum tolerated dose (MTD) and recommended phase II dose for Tomudex and Doxorubicin when given in combination to patients with advanced metastatic cancer. The secondary objective was to assess the toxicity profile. PATIENTS AND METHODS:Star...

journal_title：Investigational new drugs

authors： Bjarnason GA,Charpentier D,Wong R,Goel R,Douglas L,Walsh W,Matthews S,Dent S,Seymour L,Winquist E

更新日期：2005-01-01 00:00:00

abstract：PURPOSE:ZD0473 (AMD473) [cis-amminedichloro(2-methylpyridine) platinum(II)] is a novel platinum agent of proven activity in vitro against a variety of human tumor-derived cell lines even with intrinsic or acquired resistance to CDDP. The aim of this study is to provide the basis for a rational design of ZD0473-based co...

journal_title：Investigational new drugs

authors： Plasencia C,Abad A,Martinez-Balibrea E,Taron M

更新日期：2004-11-01 00:00:00

abstract：:SJG-136 is a synthetic pyrrolobenzodiazepine (PBD) dimer in which two DNA-alkylating subunits are linked through an inert propanedioxy tether. Biophysical and biochemical studies of SJG-136 have shown a remarkable affinity for DNA and potent cytotoxicity in vitro. On this basis, together with its unique sequence selec...

journal_title：Investigational new drugs

authors： Wilkinson GP,Taylor JP,Shnyder S,Cooper P,Howard PW,Thurston DE,Jenkins TC,Loadman PM

更新日期：2004-08-01 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

authors： Kindler HL,Avadhani A,Wade-Oliver K,Karrison T,Mani S,Vokes EE

更新日期：2004-08-01 00:00:00

abstract：:We investigated proliferation and apoptosis induction in Jurkat T-leukemia cells by the new isothiocyanate 4-(methylthio)butylisothiocyanate (MTBITC). To help elucidate whether the effects of MTBITC are specific for cancer cells, we tested MTBITC on freshly isolated, non-transformed human peripheral T lymphocytes. The...

journal_title：Investigational new drugs

authors： Fimognari C,Nüsse M,Iori R,Cantelli-Forti G,Hrelia P

更新日期：2004-04-01 00:00:00

abstract：:Cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N(4)]-chloride platinum (II) monohydrochloride monohydrate (DPR) is a new platinum triamine complex obtained from the synthesis of cisplatin and procaine. In this paper we analyzed, adopting a disease-oriented strategy, the tumour selectivity of this compound...

journal_title：Investigational new drugs

authors： Mariggiò MA,Cafaggi S,Ottone M,Parodi B,Vannozzi MO,Mandys V,Viale M

更新日期：2004-01-01 00:00:00

abstract：PURPOSE:To compare two different infusion schedules of phenylacetate (PA) in patients with primary brain tumors and to assess the feasibility of the administration in a multi-institutional setting. PATIENTS AND METHODS:Adult patients with recurrent primary brain tumors were treated with PA on two different schedules. ...

journal_title：Investigational new drugs

authors： Chang SM,Kuhn JG,Ian Robins H,Clifford Schold S,Spence AM,Berger MS,Mehta MP,Pollack I,Gilbert M,Prados MD

更新日期：2003-11-01 00:00:00

abstract：:Certain toxic effects of cytotoxic anticancer agents typically evolve over weeks. When such agents are administered weekly, these effects are cumulative. With such schedules, good medical practice mandates dose modifications with mild or moderate toxicity in order to avoid progression to serious or life-threatening to...

journal_title：Investigational new drugs

authors： McClish DK,Roberts JD

更新日期：2003-08-01 00:00:00

abstract：:Preclinical studies, along with Phase I, II, and III clinical trials demonstrate the pharmacokinetics, pharmacodynamics, safety and efficacy of a new drug under well controlled circumstances in relatively homogeneous populations. However, these types of studies generally do not answer important questions about variabi...

journal_title：Investigational new drugs

authors： Blesch KS,Gieschke R,Tsukamoto Y,Reigner BG,Burger HU,Steimer JL

更新日期：2003-05-01 00:00:00

abstract：:Imidazolium-trans-dimethylsulfoxideimidazoletetrachlororuthenate (NAMI-A) is a ruthenium compound effective on solid tumor metastases. In this study, we evaluated the effects of different routes of administration of NAMI-A on the distribution to primary tumor, lungs and kidneys in BD2F1 hybrids with Lewis lung carcino...

journal_title：Investigational new drugs

authors： Cocchietto M,Zorzet S,Sorc A,Sava G

更新日期：2003-02-01 00:00:00

abstract：PURPOSE:To investigate the hypothesis that a systemic agent designed to inhibit dihydropyrimidine dehydrogenase (DPD), the first enzyme in the fluoropyrimidine degradative pathway, could improve the effective amount of 5-fluorouracil (5-FU) delivered to a tumor resulting in enhanced response. PATIENTS AND METHODS:Elig...

journal_title：Investigational new drugs

authors： Leichman CG,Chansky K,Macdonald JS,Doukas MA,Budd GT,Giguere JK,Abbruzzese JL,Southwest Oncology Group.

更新日期：2002-11-01 00:00:00

abstract：:The aim of this study was to determine the antitumor activity of irofulven when administered in combination with a variety of antimitotic agents. Irofulven in combination with either paclitaxel or docetaxel demonstrated synergistic activity in both the in vitro and in vivo studies. The majority of xenograft bearing an...

journal_title：Investigational new drugs

authors： Kelner MJ,McMorris TC,Rojas RJ,Trani NA,Velasco TR,Estes LA,Suthipinijtham P

更新日期：2002-08-01 00:00:00

abstract：:Sixteen patients with stage IV melanoma, who were heavily pretreated, received 11 mg/m2/day of intravenous Irofulven for five consecutive days every 28 days. There were no objective tumor responses, although one patient exhibited stable disease after 4 cycles. The most common toxicities were grade 1/2 nausea, vomiting...

journal_title：Investigational new drugs

authors： Pierson AS,Gibbs P,Richards J,Russ P,Eckhardt SG,Gonzalez R

更新日期：2002-08-01 00:00:00

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：: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：:The population approach has been implemented prospectively in the clinical development of docetaxel (Taxotere). Overall 640 patients were evaluable for the population PK/PD analysis. The PK analysis evidenced significant covariates explaining the inter-patient variability of docetaxel clearance and the PK/PD analysis ...

journal_title：Investigational new drugs

authors： Bruno R,Vivier N,Veyrat-Follet C,Montay G,Rhodes GR

更新日期：2001-05-01 00:00:00

abstract：:Six patients with incurable malignancies were originally treated with vitamin E, 3200 IU/day for fourteen days, followed by the same dose of vitamin E daily plus LCV (20 mg/m2 i.v. bolus daily x 5) with 5FU (425 mg/m2 i.v. bolus immediately following LCV). The same schedule of LCV and 5FU was repeated 4 weeks later, t...

journal_title：Investigational new drugs

authors： Blanke CD,Stipanov M,Morrow J,Rothenberg M,Chinery R,Shyr Y,Coffey R,Johnson DH,Leach SD,Beauchamp RD

更新日期：2001-01-01 00:00:00

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

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

abstract：:A phase II trial of gemcitabine (Gemzar), a nucleoside analogue with broad activity in solid tumors, was performed in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. A total of 26 eligible patients were registered to receive a dose of 1250 mg/m2 weekly for 3 weeks, followed by a 1 w...

journal_title：Investigational new drugs

authors： Samlowski WE,Gundacker H,Kuebler JP,Giguere JK,Mills GM,Schuller DE,Ensley JF

更新日期：2001-01-01 00:00:00

abstract：:Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a novel fluoropyrimidine carbamate, which was designed to be sequentially converted to 5-fluorouracil (5-FU) by three enzymes located in the liver and in tumors; the final step is the conversion of 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-FU by thymidine ...

journal_title：Investigational new drugs

authors： Ishitsuka H

更新日期：2000-11-01 00:00:00

abstract：:Ninhydrin (2,2-dihydroxy-1,3-indane dione) was evaluated for its antitumor and cytotoxic properties in Ehrlich ascites carcinoma cell (EAC Cell)-bearing mice. The rationale behind this study has been mainly the literature reports of its characteristic interference with DNA synthesis and calcium homeostasis. Antitumor ...

journal_title：Investigational new drugs

authors： Qureshi S,Al-Shabanah OA,Al-Bekairi AM,Al-Harbi MM,Al-Gharably NM,Raza M

更新日期：2000-08-01 00:00:00

abstract：:UCN-01 is undergoing Phase I evaluation and is a candidate for combination strategies in the clinic. UCN-01 has been shown to have a variety of effects on cellular targets and the cell cycle. It has also been reported to sensitize cells to several clinical drugs in vitro, possibly in a manner related to p53 status. Th...

journal_title：Investigational new drugs

authors： Monks A,Harris ED,Vaigro-Wolff A,Hose CD,Connelly JW,Sausville EA

更新日期：2000-05-01 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：: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：:Estrogens play a central role in reproductive physiology. The cellular effects of estrogens are mediated by binding to nuclear receptors (ER) which activate transcription of genes involved in cellular growth control. At least two such receptors, designated ERalpha and ERbeta, mediate these effects in conjunction with ...

journal_title：Investigational new drugs

authors： Dhingra K

更新日期：1999-01-01 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：: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：BACKGROUND:Preclinical data suggested that sustained inhibition of the anabolic enzyme, ribonucleotide reductase (RR), by hydroxyurea (HU) may be critical for the anticancer effects of the drug. A phase I trial of continuous infusion HU with concomitant hyperfractionated, accelerated radiation therapy (CHU-CHRT) was in...

journal_title：Investigational new drugs

authors： Beitler JJ,Smith RV,Haynes H,Silver CE,Quish A,Kotz T,Serrano M,Brook A,Wadler S

更新日期：1998-01-01 00:00:00

abstract：:XK469 (NSC 656889) is a water-soluble member of the novel quinoxaline family of antitumor agents. In vitro, XK469 demonstrated selective cytotoxicity for several murine solid tumors including colorectal and mammary adenocarcinoma cell lines, when compared to both leukemia and normal epithelial cells. In vivo, XK469 wa...

journal_title：Investigational new drugs

authors： LoRusso PM,Parchment R,Demchik L,Knight J,Polin L,Dzubow J,Behrens C,Harrison B,Trainor G,Corbett TH

更新日期：1998-01-01 00:00:00

abstract：:Up to 30% of patients with advanced germ cell tumors will fail induction chemotherapy or will relapse. New agents with activity in this still potentially curable subgroup of patients are needed. Edatrexate (10-ethyl, 10-deaza-aminopterin) is a methotrexate analogue that has preclinical and clinical activity in breast,...

journal_title：Investigational new drugs

authors： Meyers FJ,Lew D,Lara PN Jr,Williamson S,Marshall E,Balcerzak SP,Rivkin SE,Samlowski W,Crawford ED

更新日期：1998-01-01 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：:Brequinar (DUP 785; NSC 368390) is a quinoline carboxylic acid derivative that inhibits pyrimidine synthesis at the level of dihydro-orotate dehydrogenase and revealed synergy with cisplatin in preclinical models. In this study investigating the pharmacokinetic and toxicity of brequinar in combination with cisplatin, ...

journal_title：Investigational new drugs

authors： Burris HA 3rd,Raymond E,Awada A,Kuhn JG,O'Rourke TJ,Brentzel J,Lynch W,King SY,Brown TD,Von Hoff DD

更新日期：1998-01-01 00:00:00