Genomes and Genes
maximum tolerated dose
Summary: The highest dose of a biologically active agent given during a chronic study that will not reduce longevity from effects other than carcinogenicity. (from Lewis Dictionary of Toxicology, 1st ed)
Publications328 found, 100 shown here
- Gemcitabine and doxorubicin for the treatment of patients with advanced hepatocellular carcinoma: a phase I-II trialT S Yang
Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan
Ann Oncol 13:1771-8. 2002We determined the maximum tolerated dose (MTD) and then further evaluated the response rate and safety profile of gemcitabine (Gem) plus doxorubicin (Dox) in chemonaïve patients with advanced hepatocellular carcinoma (HCC).
- Application of the CFU-GM assay to predict acute drug-induced neutropenia: an international blind trial to validate a prediction model for the maximum tolerated dose (MTD) of myelosuppressive xenobioticsA Pessina
Institute of Microbiology, Milan, Italy
Toxicol Sci 75:355-67. 2003..A predictive model to calculate the human maximum tolerated dose (MTD) was set up, by adjusting a mouse-derived MTD for the differential interspecies sensitivity...
- Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1Giuseppe Giaccone
Vrije Universiteit Medical Center, Department of Oncology, De Boelelaan 1117, 1081 Amsterdam, The Netherlands
J Clin Oncol 22:777-84. 2004..Gefitinib has demonstrated encouraging efficacy in advanced NSCLC in phase II trials in pretreated patients, and a phase I trial of gefitinib in combination with gemcitabine and cisplatin showed favorable tolerability...
- A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumoursF A L M Eskens
Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands
Br J Cancer 98:80-5. 2008..No partial or complete responses were observed, stable disease lasting more than four cycles was seen in seven patients. The recommended dose for studies with BIBW 2992 for 14 days followed by 14 days off medication is 70 mg OD...
- A phase I trial to determine the safety, tolerability, and maximum tolerated dose of deforolimus in patients with advanced malignanciesChristine M Hartford
Department of Pediatrics, Cancer Research Center, and Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, Illinois 60637, USA
Clin Cancer Res 15:1428-34. 2009This was a phase I trial to determine the maximum tolerated dose and toxicity of deforolimus (AP23573, MK-8669), an inhibitor of mammalian target of rapamycin (mTOR)...
- A phase I/II radiation dose escalation study with concurrent chemotherapy for patients with inoperable stages I to III non-small-cell lung cancer: phase I results of RTOG 0117Jeffrey D Bradley
Washington University School of Medicine, St Louis, Missouri, USA
Int J Radiat Oncol Biol Phys 77:367-72. 2010..of high-dose versus standard-dose radiation therapy, this Phase I/II study was initiated to establish the maximum tolerated dose of radiation therapy in the setting of concurrent chemotherapy, using three-dimensional conformal ..
- Safety and efficacy of combining sunitinib with bevacizumab + paclitaxel/carboplatin in non-small cell lung cancerMark A Socinski
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA
J Thorac Oncol 5:354-60. 2010....
- Phase I and pharmacokinetic study of XRP6258 (RPR 116258A), a novel taxane, administered as a 1-hour infusion every 3 weeks in patients with advanced solid tumorsAlain C Mita
Institute for Drug Development, Cancer Therapy and Research Center and University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
Clin Cancer Res 15:723-30. 2009..v. infusion every 3 weeks. The study also sought to determine the maximum tolerated dose and the recommended dose, to describe the pharmacokinetic (PK) behavior of the compound, and to seek ..
- Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesotheliomaNicholas J Vogelzang
University of Chicago, Cancer Research Center, 5841 South Maryland Ave, Chicago, IL 60637, USA
J Clin Oncol 21:2636-44. 2003..We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone...
- Tumors that acquire resistance to low-dose metronomic cyclophosphamide retain sensitivity to maximum tolerated dose cyclophosphamideUrban Emmenegger
Molecular and Cellular Biology Research, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada
Neoplasia 13:40-8. 2011..LDM) chemotherapy is emerging as an alternative or supplemental dosing strategy to conventional maximum tolerated dose (MTD) chemotherapy...
- Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomasHoward A Burris
The Sarah Cannon Research Institute, 250 25th Avenue N, Suite 110, Nashville, TN 37203, USA
J Clin Oncol 23:5305-13. 2005....
- Phase I study of everolimus plus weekly paclitaxel and trastuzumab in patients with metastatic breast cancer pretreated with trastuzumabFabrice Andre
Breast Cancer Unit, Department of Medical Oncology, University Paris XI and Institut Gustave Roussy, Villejuif, France
J Clin Oncol 28:5110-5. 2010....
- Phase I and pharmacokinetic study of YM155, a small-molecule inhibitor of survivinAnthony W Tolcher
Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX, USA
J Clin Oncol 26:5198-203. 2008..To determine the maximum-tolerated dose (MTD) and assess the safety, pharmacokinetics, and preliminary evidence of antitumor activity of YM155, a small-molecule inhibitor of survivin...
- Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2Roy S Herbst
Department of Thoracic Head and Neck Medical Oncology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX 77030, USA
J Clin Oncol 22:785-94. 2004..This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC...
- A phase I study of eribulin mesylate (E7389), a mechanistically novel inhibitor of microtubule dynamics, in patients with advanced solid malignanciesSanjay Goel
Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA
Clin Cancer Res 15:4207-12. 2009..This phase I study determined the maximum tolerated dose (MTD) and pharmacokinetics of eribulin administered on a 3 of 4 week schedule in patients with advanced ..
- IL-21 induces in vivo immune activation of NK cells and CD8(+) T cells in patients with metastatic melanoma and renal cell carcinomaKlaus Stensgaard Frederiksen
Novo Nordisk A S, Novo Nordisk Park, Maalov, Denmark
Cancer Immunol Immunother 57:1439-49. 2008..Here we report the effects of systemic IL-21 therapy on the immune system in two phase 1 trials with this novel cytokine...
- Silica nanoparticles administered at the maximum tolerated dose induce genotoxic effects through an inflammatory reaction while gold nanoparticles do notThomas R Downs
The Procter and Gamble Co, Miami Valley Innovation Center, 11810 East Miami River Road, Cincinnati, OH 45252, USA
Mutat Res 745:38-50. 2012..a small but reproducible increase in DNA damage and micronucleated reticulocytes when tested at their maximum tolerated dose (MTD). No genotoxic effects were observed at lower doses, and the in vitro MN assay was also negative...
- An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancerM Kozloff
Department of Oncology, Cancer Research Center, Ingalls Memorial Hospital, Harvey, IL60426, USA
Ann Oncol 21:1436-41. 2010..We investigated the safety of the combination of sunitinib and paclitaxel in an exploratory study of patients with locally advanced or MBC...
- A modified Phase I trial of radiation dose escalation in 3D conformal radiation therapy with concurrent vinorelbine and carboplatin chemotherapy for non-small-cell lung cancerQiang Lin
Department of Oncology, Hebei Medical University North China Petroleum Bureau General Hospital, 8 Huizhan Avenue, Renqiu 062552, Hebei, China
J Radiat Res 54:126-34. 2013The Radiation Therapy Oncology Group reported a maximum tolerated dose of 74 Gy for patients with non-small cell lung cancer (NSCLC); however, it was unclear whether this dose could be safely administered to Asian patients due to ..
- Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexusFeng Ming Spring Kong
Department of Radiation Oncology, University of Michigan and Ann Arbor Veteran Affairs Medical System, Ann Arbor, MI 48109, USA
Int J Radiat Oncol Biol Phys 81:1442-57. 2011....
- A phase I single-agent study of twice-weekly consecutive-day dosing of the proteasome inhibitor carfilzomib in patients with relapsed or refractory multiple myeloma or lymphomaMelissa Alsina
H Lee Moffitt Cancer and Research Center, Tampa, FL 33612, USA
Clin Cancer Res 18:4830-40. 2012..The objectives of this phase I study were to establish the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of escalating doses of carfilzomib in patients with relapsed or refractory hematologic malignancies...
- Heterogeneity in the definition of dose-limiting toxicity in phase I cancer clinical trials of molecularly targeted agents: a review of the literatureChristophe Le Tourneau
Department of Medical Oncology, Institut Curie, Paris, France
Eur J Cancer 47:1468-75. 2011..There is no consensus about what constitutes a dose-limiting toxicity (DLT) in phase I cancer clinical trials. We aimed to evaluate how DLTs are defined in phase I trials of molecularly targeted agents (MTA)...
- Phase I dose escalation and pharmacokinetic study of BI 2536, a novel Polo-like kinase 1 inhibitor, in patients with advanced solid tumorsKlaus Mross
Tumor Biology Center at the Albert Ludwigs University Freiburg, Breisacherstrasse 117, D 79106, Freiburg, Germany
J Clin Oncol 26:5511-7. 2008..The aim of this trial was to identify the maximum tolerated dose (MTD) of BI 2536 and to determine the safety, pharmacokinetics, and antitumor activity in patients who had ..
- Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphomaQin C Ryan
Clinical Trials Unit, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA
J Clin Oncol 23:3912-22. 2005..The objective of this study was to define the maximum-tolerated dose (MTD), the recommended phase II dose, the dose-limiting toxicity, and determine the pharmacokinetic (PK) and pharmacodynamic profiles of MS-275...
- Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumorsJosep Tabernero
Medical Oncology Department, Vall d Hebron University Hospital, Universitat Autonoma de Barcelona, corrected Barcelona, Spain
J Clin Oncol 26:1603-10. 2008..In order to identify a rationally based dose and schedule for cancer treatment, we have conducted a tumor pharmacodynamic phase I study in patients with advanced solid tumors...
- Phase I study of the heat shock protein 90 inhibitor alvespimycin (KOS-1022, 17-DMAG) administered intravenously twice weekly to patients with acute myeloid leukemiaJ E Lancet
H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Leukemia 24:699-705. 2010..The twice-weekly administered alvespimycin was well tolerated in patients with advanced AML, showing linear pharmacokinetics, target inhibition and signs of clinical activity. We determined a recommended phase 2 dose of 24 mg/m(2)...
- Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicinY Matsumura
Investigative Treatment Division, National Cancer Center Research Institute East, 6 5 1 Kashiwanoha, Kashiwa 277 8577, Japan
Br J Cancer 91:1775-81. 2004..NK911 was well tolerated and produced only moderate nausea and vomiting at myelosuppressive dosages. The recommended phase II dose was determined to be 50 mg m(-2) every 3 weeks...
- Phase I trial and pharmacokinetic study of bevacizumab in pediatric patients with refractory solid tumors: a Children's Oncology Group StudyJulia L Glade Bender
College of Physicians and Surgeons of Columbia University, New York, NY, USA
J Clin Oncol 26:399-405. 2008..Primary aims included estimating the maximum-tolerated dose (MTD) and determining the dose-limiting toxicities (DLTs), pharmacokinetics, and biologic effects of BV in children with cancer...
- Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized phase II trialW Scheithauer
Division of Oncology, Department of Internal Medicine I, Vienna University Medical School, Vienna, Austria
Ann Oncol 14:97-104. 2003..Based on this background and in order to define the therapeutic potential and tolerance of this combination more precisely, the present randomized multicenter phase II trial was initiated...
- A phase I study of oral panobinostat alone and in combination with docetaxel in patients with castration-resistant prostate cancerDana Rathkopf
Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Cancer Chemother Pharmacol 66:181-9. 2010..We aimed to define the maximum tolerated dose, toxicity, activity, and pharmacokinetics of oral panobinostat, a pan-deacetylase inhibitor, alone and in ..
- Phase I study of eribulin mesylate administered once every 21 days in patients with advanced solid tumorsAntoinette R Tan
The Cancer Institute of New Jersey, New Brunswick, New Jersey 08901, USA
Clin Cancer Res 15:4213-9. 2009To evaluate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of eribulin mesylate (E7389), a halichondrin B analogue, administered every 21 days in patients with advanced solid tumors.
- Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignanciesDavid W Nyman
Department of Pharmacology Toxicology, Division of Hematology Oncology, Arizona Cancer Center University of Arizona Health Sciences Center, Tucson, USA
J Clin Oncol 23:7785-93. 2005..This study determined the maximum-tolerated dose (MTD) of ABI-007 monotherapy administered weekly (three weekly doses, repeated every 4 weeks) and assessed the pharmacokinetics of paclitaxel administered as ABI-007...
- Results of a Phase I trial of concurrent chemotherapy and escalating doses of radiation for unresectable non-small-cell lung cancerSteven E Schild
Mayo Clinic and Mayo Foundation, Rochester, MN, USA
Int J Radiat Oncol Biol Phys 65:1106-11. 2006This trial was performed to determine the maximum tolerated dose (MTD) of radiation that can be administered with carboplatin and paclitaxel.
- Phase I pharmacokinetic and pharmacodynamic study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin, an inhibitor of heat-shock protein 90, in patients with advanced solid tumorsRamesh K Ramanathan
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
J Clin Oncol 28:1520-6. 2010To define the maximum tolerated dose, toxicities, pharmacokinetics, and pharmacodynamics of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17DMAG).
- Phase 1 study of aflibercept administered subcutaneously to patients with advanced solid tumorsWilliam P Tew
Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Clin Cancer Res 16:358-66. 2010To determine the maximum tolerated dose or maximal administered dose and pharmacokinetic and safety profiles of s.c. administered vascular endothelial growth factor Trap (aflibercept), a novel antiangiogenic agent.
- Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancerWilliam Kevin Kelly
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Joan and Sanford Weill Medical College of Cornell University, New York, NY 10021, USA
J Clin Oncol 23:3923-31. 2005..To determine the safety, dosing schedules, pharmacokinetic profile, and biologic effect of orally administered histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with advanced cancer...
- Preoperative concurrent chemotherapy with S-1 and radiotherapy for locally advanced squamous cell carcinoma of the oral cavity: phase I trialHiroyuki Harada
Department of Oral Surgery, Oral Restitution, Division of Oral Health Sciences, Graduate School, Tokyo Medical and Dental University, Japan
J Exp Clin Cancer Res 29:33. 2010..This study was conducted to identify a recommended dose for S-1, used in combination with 40-Gy radiation...
- Phase I clinical trial of fixed-dose rate infusional gemcitabine and dacarbazine in the treatment of advanced soft tissue sarcoma, with assessment of gemcitabine triphosphate accumulationJose M Buesa
Servicio de Oncologia Medica, Instituto Universitario de Oncologia del Principado de Asturias, Hospital Central de Asturias, Oviedo, Spain
Cancer 101:2261-9. 2004In the current study, the authors set out to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) associated with a combination of gemcitabine and dacarbazine (DTIC) in patients with advanced soft tissue sarcoma (..
- A modified toxicity probability interval method for dose-finding trialsYuan Ji
Department of Bioinformatics and Computational Biology, The University of Texas M D Anderson Cancer Center, Houston, TX, USA
Clin Trials 7:653-63. 2010..Building on earlier work, the toxicity probability interval (TPI) method, we present a modified TPI (mTPI) design that is calibration-free for phase I trials...
- Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancerK Yamaguchi
Department of Gastroenterology, Saitama Cancer Centre, Ina machi, Kitaadachi gun, Japan
Br J Cancer 94:1803-8. 2006..3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer...
- The maximum tolerated dose and biologic effects of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) in combination with irinotecan for patients with refractory solid tumorsBrian S Choi
University of Wisconsin Paul P Carbone Comprehensive Cancer Center, Madison, WI, 53792, USA
Cancer Chemother Pharmacol 66:973-80. 2010..This study was conducted to determine the toxicity and antitumor activity of 3-AP with irinotecan. Correlative studies included pharmacokinetics and the effects of ABCB1 and UGT1A1 polymorphisms...
- A phase 1 study of everolimus and sorafenib for metastatic clear cell renal cell carcinomaAndrea L Harzstark
Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143 1711, USA
Cancer 117:4194-200. 2011The current study was conducted to assess the maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor effect of everolimus, a mammalian target of rapamycin inhibitor, in combination with sorafenib, a tyrosine ..
- The continual reassessment method: comparison of Bayesian stopping rules for dose-ranging studiesS Zohar
Departement de Biostatistique et Informatique Medicale, Hopital Saint Louis, Universite Paris 7, U444 INSERM, France
Stat Med 20:2827-43. 2001The continual reassessment method (CRM) provides a Bayesian estimation of the maximum tolerated dose (MTD) in phase I clinical trials and is also used to estimate the minimal efficacy dose (MED) in phase II clinical trials...
- Objective response of multiply recurrent low-grade gliomas to bevacizumab and irinotecanRoger J Packer
Division of Neurology, Children s National Medical Center, Washington, District of Columbia 20010, USA
Pediatr Blood Cancer 52:791-5. 2009..Bevacizumab, a humanized immunoglobulin, monoclonal antibody that inhibits the activity of vascular endothelial growth factor and irinotecan have been used with some success in adults with malignant gliomas...
- Safety, pharmacokinetics, and biological pharmacodynamics of the immunocytokine EMD 273066 (huKS-IL2): results of a phase I trial in patients with prostate cancerYoo Joung Ko
Beth Israel Deaconess Medical Center, Boston, MA, USA
J Immunother 27:232-9. 2004This phase 1 clinical trial was conducted to evaluate the safety and to determine the maximum tolerated dose (MTD) of the immunocytokine EMD 273066 huKS-IL2 and, secondarily, to assess its pharmacokinetics, immunogenic potential, and ..
- VEGF receptor inhibitors block the ability of metronomically dosed cyclophosphamide to activate innate immunity-induced tumor regressionJoshua C Doloff
Division of Cell and Molecular Biology, Department of Biology, Boston University, Boston, Massachusetts 02215, USA
Cancer Res 72:1103-15. 2012..Cyclophosphamide administered at a maximum tolerated dose activated a transient, weak innate immune response, arguing that persistent drug-induced cytotoxic damage ..
- An open-label, two-arm, phase I trial of recombinant human interleukin-21 in patients with metastatic melanomaIan D Davis
Austin Health, Melbourne, Victoria, Australia
Clin Cancer Res 13:3630-6. 2007....
- Cabazitaxel in patients with advanced solid tumours: results of a Phase I and pharmacokinetic studyV Dieras
Department of Medical Oncology, Institut Curie, 26 Rue d Ulm, 75231 Paris Cedex 5, France
Eur J Cancer 49:25-34. 2013..Cabazitaxel is a novel taxane active in both preclinical models of chemotherapy-sensitive and -resistant human tumours and patients with advanced prostate cancer that progressed following docetaxel treatment...
- Pharmacokinetic evaluation of the vinorelbine-lapatinib combination in the treatment of breast cancer patientsKeyvan Rezai
Institut Curie Hôpital René Huguenin, Saint Cloud, France
Cancer Chemother Pharmacol 68:1529-36. 2011..The objectives of this study were to investigate the pharmacokinetics of intra-venous vinorelbine combined with lapatinib as well as the effect of covariates in breast cancer patients...
- Choice of starting dose for molecularly targeted agents evaluated in first-in-human phase I cancer clinical trialsChristophe Le Tourneau
Division of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada
J Clin Oncol 28:1401-7. 2010..There is no consensus on which preclinical models and parameters should define the starting dose for molecularly targeted agents...
- Continual reassessment method for ordered groupsJOHN O'QUIGLEY
Department of Biostatistics, Institut Curie, 75005 Paris, France
Biometrics 59:430-40. 2003..we have little or almost no knowledge about which of the available dose levels will correspond to the maximum tolerated dose (MTD), but we may have quite strong knowledge concerning which of the two groups will have the higher ..
- Weekly paclitaxel as second-line chemotherapy for advanced or recurrent gastric cancerShuichi Hironaka
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Shizuoka, 411 8777, Japan
Gastric Cancer 9:14-8. 2006..We investigated, retrospectively, the antitumor effects and toxicity profiles of weekly paclitaxel for patients with metastatic or recurrent gastric cancer in clinical practice...
- Phase I and pharmacokinetic study of two different schedules of oxaliplatin, irinotecan, Fluorouracil, and leucovorin in patients with solid tumorsMatthew P Goetz
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
J Clin Oncol 21:3761-9. 2003..Additionally, we investigated the effect of CPT-11 on oxaliplatin pharmacokinetics...
- Phase I and pharmacokinetic study of UCN-01 in combination with irinotecan in patients with solid tumorsAntonio Jimeno
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Cancer Research Building I, Baltimore, MD, USA
Cancer Chemother Pharmacol 61:423-33. 2008..I inhibitors and non-overlapping toxicity, UCN-01 and irinotecan were combined in a dose-finding study designed to determine the maximum tolerated dose (MTD), toxicity profile, and pharmacokinetics (PK) of UCN-01 and irinotecan.
- Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023Karen Kelly
University of Kansas Medical Center, Kansas City, KS 66160, USA
J Clin Oncol 26:2450-6. 2008..Early clinical studies with gefitinib showed promising efficacy and mild toxicity in patients with advanced non-small-cell lung cancer (NSCLC). Thus, gefitinib was an ideal agent to evaluate in a maintenance setting in stage III disease...
- Phase I clinical and pharmacokinetic study of PNU166945, a novel water-soluble polymer-conjugated prodrug of paclitaxelJ M Meerum Terwogt
The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Anticancer Drugs 12:315-23. 2001..Consequently, the safety profile may differ significantly from standard paclitaxel...
- Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignanciesM Hidalgo
Institute for Drug Development, Cancer Therapy and Research Center, and The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
J Clin Oncol 19:3267-79. 2001..To assess the feasibility of administering OSI-774, to recommend a dose on a protracted, continuous daily schedule, to characterize its pharmacokinetic behavior, and to acquire preliminary evidence of anticancer activity...
- Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancerC J McGinn
Department of Radiation Oncology, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109 0010, USA
J Clin Oncol 19:4202-8. 2001..The primary objective of this phase I trial was to determine the maximum-tolerated dose of radiation that could be delivered to the primary tumor concurrent with full-dose gemcitabine in patients with advanced pancreatic cancer...
- Phase I/II study of the mammalian target of rapamycin inhibitor everolimus (RAD001) in patients with relapsed or refractory hematologic malignanciesKaren W L Yee
Authors Affiliations Departments of Leukemia and Blood and Marrow Transplantation, University of Texas M D Anderson Cancer Center, Houston, Texas
Clin Cancer Res 12:5165-73. 2006..A phase I/II study was done to determine safety and efficacy of everolimus in patients with relapsed or refractory hematologic malignancies...
- Evaluation in melanoma-bearing mice of an etoposide derivative associated to a cholesterol-rich nano-emulsionAna C Lo Prete
Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil
J Pharm Pharmacol 58:801-8. 2006..The maximum tolerated dose (MTD), tissue distribution, plasma decay curves, pharmacokinetic parameters and antitumoral activity were ..
- Phase I study of the angiogenesis inhibitor BIBF 1120 in patients with advanced solid tumorsKlaus Mross
Tumour Biology Center and Department of Radiology, Section MR Development, Albert Ludwigs Universitat Freiburg, Freiburg, Germany
Clin Cancer Res 16:311-9. 2010..This phase I, accelerated titration study assessed the maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamic effects of BIBF 1120.
- In vitro and in vivo pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine and CYC202Florence I Raynaud
Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, Haddow Laboratories, Belmont, Sutton, United Kingdom
Clin Cancer Res 11:4875-87. 2005..To investigate pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine, and CYC202 (R-roscovitine; seliciclib) in the HCT116 human colon carcinoma model...
- A phase I open-label dose-escalation study of oral BIBF 1120 combined with standard paclitaxel and carboplatin in patients with advanced gynecological malignanciesA Du Bois
Department of Gynecology and Gynecologic Oncology, Dr Horst Schmidt Klinik HSK, Wiesbaden, Germany
Ann Oncol 21:370-5. 2010The purpose of the phase I dose-escalation study was to evaluate the maximum tolerated dose (MTD) of BIBF 1120, an oral triple angiokinase inhibitor of vascular endothelial growth factor, platelet derived growth factor and fibroblast ..
- Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphomaElise A Olsen
Duke University, Durham, NC, USA
J Clin Oncol 25:3109-15. 2007....
- Modulation of cell cycle progression in human tumors: a pharmacokinetic and tumor molecular pharmacodynamic study of cisplatin plus the Chk1 inhibitor UCN-01 (NSC 638850)Raymond P Perez
Section of Hematology Oncology, Department of Medicine, Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, USA
Clin Cancer Res 12:7079-85. 2006..A phase I trial tested the hypothesis that UCN-01 abrogates cisplatin-induced cell cycle arrest (in tumors) at tolerable doses...
- Phase I trial of combined-modality therapy for localized esophageal cancer: escalating doses of continuous-infusion paclitaxel with cisplatin and concurrent radiation therapyBaruch Brenner
Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
J Clin Oncol 22:45-52. 2004..To define the maximum-tolerated dose (MTD) of paclitaxel when given as a weekly 96-hour infusion with cisplatin and radiotherapy for patients with esophageal cancer...
- A predictive model of human myelotoxicity using five camptothecin derivatives and the in vitro colony-forming unit granulocyte/macrophage assayNoriko Masubuchi
Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co, Ltd, Tokyo, Japan
Clin Cancer Res 10:6722-31. 2004..The purpose of this study was to establish a reliable method to predict the human maximum tolerated dose (MTD) of five camptothecin derivatives: SN-38, DX-8951f, topotecan, 9-aminocamptothecin, and camptothecin.
- Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumorsANNE O'DONNELL
Royal Marsden Hospital, Sutton, Surrey, UK
J Clin Oncol 26:1588-95. 2008..To identify the optimal regimen and dosage of the oral mammalian target of rapamycin inhibitor everolimus (RAD001)...
- Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myelomaPaul G Richardson
Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
Blood 100:3063-7. 2002..Our study therefore provides the basis for the evaluation of CC-5013, either alone or in combination, to treat patients with MM at earlier stages of disease...
- Phase I oncology studies: evidence that in the era of targeted therapies patients on lower doses do not fare worseRajul K Jain
Department of Investigational Cancer Therapeutics, Phase I Program, MD Anderson Cancer Center, Houston, Texas 77030 4009, USA
Clin Cancer Res 16:1289-97. 2010..Doses are successively increased until the maximum tolerated dose (MTD) is determined...
- Irinotecan is active in chemonaive patients with metastatic gastric cancer: a phase II multicentric trialC H Kohne
Robert Rossle Klinik, Charite University Hospital, Berlin, Germany
Br J Cancer 89:997-1001. 2003..1%. Febrile neutropenia occurred in 12.5% of patients. These findings indicate that irinotecan is active and well tolerated in patients with metastatic gastric adenocarcinoma and warrants further evaluation in this clinical setting...
- Imatinib mesylate for targeting the platelet-derived growth factor beta receptor in combination with fluorouracil and leucovorin in patients with refractory pancreatic, bile duct, colorectal, or gastric cancer--a dose-escalation Phase I trialSalah Eddin Al-Batran
Department of Hematology and Oncology, Krankenhaus Nordwest, Frankfurt am Main, Germany
Cancer 109:1897-904. 2007..The objective of this Phase I study was to define the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of imatinib in combination with fluorouracil and leucovorin in patients with chemotherapy-refractory ..
- Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trialRoy S Herbst
Department of Thoracic Head and Neck Medical Oncology, University of Texas M D Anderson Cancer Center, Houston, TX, USA
J Clin Oncol 20:3815-25. 2002....
- Phase I trial of sunitinib and gemcitabine in patients with advanced solid tumorsJoanna M Brell
University Hospitals Seidman Cancer Center, Cleveland, OH, USA
Cancer Chemother Pharmacol 70:547-53. 2012..Combining small-molecule kinase inhibitors of VEGFR with chemotherapy has yet to demonstrate clinical benefit. The dose, schedule and agents used may be critical to the development of this combinatorial therapy...
- Decreased exposure to sunitinib due to concomitant administration of ifosfamide: results of a phase I and pharmacokinetic study on the combination of sunitinib and ifosfamide in patients with advanced solid malignanciesP Hamberg
Department of Medical Oncology, Erasmus University Medical Center Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
Br J Cancer 102:1699-706. 2010..This study aimed to define the maximally tolerated dose (MTD) of sunitinib combined with two different infusion schedules of ifosfamide...
- Phase I study of intermittent and chronomodulated oral therapy with capecitabine in patients with advanced and/or metastatic cancerDaniele Santini
Medical Oncology, University Campus Bio Medico, Rome, Italy
BMC Cancer 6:42. 2006....
- Predictors for establishing recommended phase 2 doses: analysis of 320 dose-seeking oncology phase 1 trialsNicolas Penel
Département de Cancérologie Générale, Centre Oscar Lambret, 3 Rue F Combemale, 59020 Lille, France
Invest New Drugs 30:653-61. 2012For 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...
- A randomized, open-label, phase I/II trial to investigate the maximum tolerated dose of the Polo-like kinase inhibitor BI 2536 in elderly patients with refractory/relapsed acute myeloid leukaemiaCarsten Muller-Tidow
Department of Medicine, Haematology and Oncology, University of Munster, Munster, Germany
Br J Haematol 163:214-22. 2013..b>Maximum tolerated dose was 350 and 200 mg in the day 1 and days 1 + 8 schedules, respectively...
- A novel toxicity scoring system treating toxicity response as a quasi-continuous variable in Phase I clinical trialsZhengjia Chen
Rollins School of Public Health, Emory University, Atlanta, GA 30322, United States
Contemp Clin Trials 31:473-82. 2010..of EID to the data of a real Phase I trial demonstrate that EID can always estimate a more accurate maximum tolerated dose (MTD) according to the exact toxicity profile under any toxicity profiles without additional cost or ..
- A phase I and pharmacokinetic study of MAG-CPT, a water-soluble polymer conjugate of camptothecinN E Schoemaker
Department of Medical Oncology, Antoni van Leeuwenhoek Hospital The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
Br J Cancer 87:608-14. 2002..Haematological toxicity was relatively mild, but serious bladder toxicity was encountered which is typical for camptothecin and was found dose limiting...
- Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancerMatthew P Goetz
Division of Medical Oncology, Mayo Clinic College of Medicine, Rochester, MN, USA
J Clin Oncol 23:1078-87. 2005..We also characterized the pharmacokinetics of 17-AAG, its effect on chaperone and client proteins, and whether cytochrome P450 (CYP) 3A5 and NAD(P)H:quinone oxidoreductase 1 (NQO1) polymorphisms affected 17-AAG disposition or toxicity...
- Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancerJohn Marshall
Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road NW, Washington, DC 20007, USA
Future Oncol 9:271-81. 2013To determine the maximum tolerated dose (MTD), safety and anti-tumor activity of afatinib combined with docetaxel in advanced cancer.
- Phase I study of BIBF 1120 with docetaxel and prednisone in metastatic chemo-naive hormone-refractory prostate cancer patientsG Bousquet
Department of Oncology, APHP Saint Louis Hospital, Paris, France
Br J Cancer 105:1640-5. 2011..Currently, the molecule is in phase III development for second-line non-small cell lung cancer and first-line ovarian cancer patients...
- Maximum tolerated dose in a phase I trial on adaptive dose painting by numbers for head and neck cancerIndira Madani
Department of Radiotherapy, Ghent University Hospital, Belgium
Radiother Oncol 101:351-5. 2011To determine the maximum tolerated dose (MTD) in a phase I trial on adaptive dose-painting-by-numbers (DPBN) for non-metastatic head and neck cancer.
- Nature and subjectivity of dose-limiting toxicities in contemporary phase 1 trials: comparison of cytotoxic versus non-cytotoxic drugsNicolas Penel
Centre Oscar Lambret, 3 Rue Frederic Combemale, 59020, Lille Cedex, France
Invest New Drugs 29:1414-9. 2011..Approximately 50% of dose-finding phase 1 trials investigating non-cytotoxic drugs led to DLT and then the maximum tolerated dose being found...
- Phase I study of bortezomib and cetuximab in patients with solid tumours expressing epidermal growth factor receptorA Z Dudek
Division of Hematology, Department of Medicine, Oncology and Transplantation, Comprehensive Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
Br J Cancer 100:1379-84. 2009..The aim of this phase I trial was to establish the maximum tolerated dose (MTD) for bortezomib plus cetuximab in patients with EGFR-expressing epithelial tumours...
- A Phase I study of gemcitabine with concurrent radiotherapy in stage III, locally advanced non-small cell lung cancerJohn W G van Putten
Departments of Pulmonary Diseases, University Hospital, Groningen, 9700 RB The Netherlands
Clin Cancer Res 9:2472-7. 2003Our goal was to find the maximum tolerated dose of gemcitabine administered concurrently with thoracic radiotherapy in locally advanced non-small cell lung cancer (NSCLC).
- Phase I and pharmacokinetic study of pemetrexed plus cisplatin in chemonaive patients with locally advanced or metastatic malignant pleural mesothelioma or non-small cell lung cancerNicolas J Dickgreber
Hannover Medical School, Hannover, Germany
Clin Cancer Res 15:382-9. 2009..We evaluated the toxicity and pharmacokinetics (PK) of higher pemetrexed doses with cisplatin and vitamin supplementation...
- Phase I and pharmacokinetic trial of the novel taxane BMS-184476 administered as a 1-hour intravenous infusion in combination with cisplatin every 21 daysWeijing Sun
Abrahmson Family Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Clin Cancer Res 9:5221-7. 2003..2 +/- 4.5 h, respectively. BMS-184476 60 at mg/m(2) with cisplatin at 75 mg/m(2) with appropriate supportive therapy is the dose recommended for further evaluation...
- Phase 1 study of TAS-102 administered once daily on a 5-day-per-week schedule in patients with solid tumorsMichael J Overman
Department of Gastrointestinal Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston Texas, 1515 Holcombe Blvd, Houston, TX, 77030, USA
Invest New Drugs 26:445-54. 2008..The primary objectives were the determination of the maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended phase II dose...
- Clinical and pharmacologic study of the novel prodrug delimotecan (MEN 4901/T-0128) in patients with solid tumorsStephan A Veltkamp
Division of Experimental Therapy, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, The Netherlands
Clin Cancer Res 14:7535-44. 2008..4901/T-0128), a carboxymethyldextran polymer prodrug of the active camptothecin derivative T-2513, and to assess the maximum tolerated dose, safety profile, clinical pharmacology, and antitumor activity of delimotecan and metabolites.
- [A phase-I clinical study of a combination therapy of vinorelbine and capecitabine in patients with advanced/recurrent breast cancer]Muneaki Sano
Dept of Surgery, Niigata Cancer Center Hospital
Gan To Kagaku Ryoho 33:1091-7. 2006..They were reversible, however, and not severe enough to discontinue treatment. The response rate was 25.0% (3 PR/12). The combination with capecitabine did not affect the plasma pharmacokinetics of vinorelbine...
- Phase I and pharmacokinetic study of gimatecan given orally once a week for 3 of 4 weeks in patients with advanced solid tumorsAndrew X Zhu
Massachusetts General Hospital, Dana Farber Harvard Cancer Center, Harvard Medical School, Boston, Massachusetts 02114, USA
Clin Cancer Res 15:374-81. 2009A phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of gimatecan, a lipophilic camptothecin analogue, administered orally once a week for 3 weeks.
- The continual reassessment method for dose-finding studies: a tutorialElizabeth Garrett-Mayer
Division of Oncology Biostatistics, Johns Hopkins University, Baltimore, MD, USA
Clin Trials 3:57-71. 2006..by clinical trialists is that it tends to incur fewer toxic events, and more accurately estimate the maximum tolerated dose as compared to the standard Phase I dose escalation designs...
- A curve-free method for phase I clinical trialsM Gasparini
Dipartimento di Matematica, Politecnico di Torino, Italy
Biometrics 56:609-15. 2000..The problem is commonplace in oncology Phase I clinical trials. Such a dose is often called the maximum tolerated dose (MTD) since it represents a necessary trade-off between efficacy and toxicity...
- Phase I trial of the novel taxane BMS-184476 administered in combination with carboplatin every 21 daysJ H Bilenker
Abramson Family Cancer Center, University of Pennsylvania Cancer Center, 51 N 39th St, MAB, Philadelphia, PA 19104, USA
Br J Cancer 91:213-8. 2004..BMS-184476 in combination with carboplatin was well tolerated at a dose of 50/6 and shows evidence of antitumour activity in a pretreated population...
- Phase I and pharmacokinetic study of the orally administered farnesyl transferase inhibitor R115777 in patients with advanced solid tumorsC J Punt
Department of Medical Oncology, University Medical Center St Radboud, The Netherlands
Anticancer Drugs 12:193-7. 2001..We conclude that the recommended dose of R115777 given for 28 days followed by 1-2 weeks of rest is 300 mg b.i.d. Myelosuppression is the dose-limiting toxicity...
- Vorinostat, a histone deacetylase inhibitor, combined with pelvic palliative radiotherapy for gastrointestinal carcinoma: the Pelvic Radiation and Vorinostat (PRAVO) phase 1 studyAnne Hansen Ree
Department of Tumour Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
Lancet Oncol 11:459-64. 2010..Histone deacetylase (HDAC) inhibitors have shown radiosensitising activity in preclinical tumour models. This phase 1 study assessed the use of vorinostat combined with pelvic palliative radiotherapy for gastrointestinal carcinoma...
- A phase I biological and pharmacologic study of the heparanase inhibitor PI-88 in patients with advanced solid tumorsMichele Basche
University of Colorado Cancer Center, Aurora, Colorado 80010, USA
Clin Cancer Res 12:5471-80. 2006..This agent showed potent inhibition of placental blood vessel angiogenesis as well as growth inhibition in multiple xenograft models, thus forming the basis for this study...
- Amphotericin B preparations: a maximum tolerated dose in severe invasive fungal infections?M Ellis
Faculty of Medicine, UAE University, Al Ain, Abu Dhabi, United Arab Emirates
Transpl Infect Dis 2:51-61. 2000..b>Maximum tolerated dose studies using existing lipid formulations, or perhaps with the newer formulations such as pegylated ..
- Selective modulation of the therapeutic efficacy of anticancer drugs by selenium containing compounds against human tumor xenograftsShousong Cao
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
Clin Cancer Res 10:2561-9. 2004....
- MICELLAR CARRIERS FOR SPARINGLY SOLUBLE PHARMACEUTICALSVladimir Torchilin; Fiscal Year: 2007..To prepare PEG-PE-based micelles loaded with camptothecin and taxol; determine the maximum tolerated dose (MTD) in C57BL and nude mice; and investigate their tumor accumulation and therapeutic effect in vivo in ..
- N-methanocarbathymidine (N-MCT) for the Treatment of Herpes and Pox Virus InfectiAquilur Rahman; Fiscal Year: 2010..These studies will allow initiation of Phase I clinical trial to determine the maximum tolerated dose, toxicity, bioavailability and pharmacokinetic parameters...
- Efficacy of GABAA a5 receptor inverse agonists in learning impaired ratsEARL MICHAEL GIBBS; Fiscal Year: 2010..In this SBIR Phase I project, PhysioGenix will determine the efficacy, pharmacokinetics (PK), maximum tolerated dose and potential side-effects of PWZ-029, a benzodiazepine (BZ) compound that may prove useful for treating ..
- N-methanocarbathymidine (N-MCT) for the Treatment of Herpes and Pox Virus InfectiAquilur Rahman; Fiscal Year: 2013..allow filing an IND application for the eventual initiation of Phase I clinical trials to determine the maximum tolerated dose, side effects, bioavailability, pharmacokinetics and the starting doses for Phase IIA clinical trials in ..
- Treatment of Inflammatory Bowel Disease with Ceramidase InhibitorsLynn W Maines; Fiscal Year: 2012..The Maximum Tolerated Dose and pharmacokinetics of each of these ceramidse inhibitors will be determined to optimize treatment ..
- Development of Inhaled Vancomycin for Treatment of MRSA Infections in CFTaneli Jouhikainen; Fiscal Year: 2012..The second line of study is directed at establishing the safety and maximum tolerated dose (MTD) of AEROVANC and characterizing its pharmacokinetic profile in the lung and in blood...
- Brain Tumor-Penetrating Nanoparticle Delivery with MR-Guided Focused UltrasoundRichard J Price; Fiscal Year: 2013..In Aim 4, we will first determine the maximum tolerated dose (MTD) of paclitaxel-loaded BPNs, followed by an evaluation of drug pharmacokinetics (PK)...
- Correlative Studies for NCI Study#7916: Phase I Clinical Trial of Intravenous FAUPatricia Mucci LoRusso; Fiscal Year: 2010..on days 1-5 of a 28-day cycle, to determine the dose limiting toxicities (DLT), and to establish the maximum tolerated dose (MTD)...
- Phase 1 of AR-42 in relapsed CLL, lymphoma, myelomaCraig C Hofmeister; Fiscal Year: 2012..Mon/Wed/Fri in cycles of 28 days (three weeks on, one week off) to determine dose limiting toxicity (DLT), maximum tolerated dose (MTD), and toxicity profile of AR-42;2a) To examine circulating CLL cells from patients before and after ..
- Intratumoral genetic therapy for lung cancerSteven M Dubinett; Fiscal Year: 2013..In the context of this phase I trial in patients with advanced NSCLC we will determine the safety and maximum tolerated dose of intratumorally administered AdCCL21-DC...
- Intracellular targeting Hsp70 for pulmonary cytoprotection after toxin inhalationRichard Weisbart; Fiscal Year: 2013..2) Establish a product stability profile for the Fv-Hsp70 aerosol and determine the maximum tolerated dose (MTD) in rats...
- Targeted Radiotherapy with 90Y-BC8 Monclonal Antibody, Fludarabine and TBI FollowWilliam I Bensinger; Fiscal Year: 2012..treatment protocol will involve a 2-stage dose escalation of isotope in patients designed to determine the maximum tolerated dose of 90Y anti-CD45, when combined with fludarabine and TBI in patients with MM receiving allo SCT...
- Antitumor and chemopreventive activity of the Ecuadorian plant extract BIRMBal L Lokeshwar; Fiscal Year: 2010..In Aim 1, the minimum effective dose, optimum effective dose and maximum tolerated dose of BIRM will be established in the TRAMP (transgenic adenocarcinoma of the mouse prostate) model...
- ChNKG2D-Targeted Cellular Cancer Therapy: Preclinical ToxicologyCARIN MARIE LOUISE SENTMAN; Fiscal Year: 2010..We will complete preclinical toxicology, including determination of Maximum Tolerated Dose (MTD) for single and multiple administrations using the chimeric receptor, wild type receptor, and HBSS as ..
- Phase I Trial of Bortezomib and Romidepsin in CLL and Small Cell LymphomaSteven Grant; Fiscal Year: 2010..The specific aims of this proposal are: First, to determine the maximum tolerated dose (MTD) for the combination of bortezomib and romidepsin administered weekly x 3 every 4 weeks in patients ..
- A synthetic triterpenoid in breast cancer chemopreventionAnupam Bishayee; Fiscal Year: 2010..The chemopreventive doses will be based on an experimentally-determined maximum tolerated dose (MTD)...
- Targeting the cell cycle in triple negative breast cancerKhandan Keyomarsi; Fiscal Year: 2013..4) Phase I trial with dose expansion to determine maximum tolerated dose (MTD), response rate (RR) and biologic effects of CDK2 inhibition with roscovitine (Seliciclib) given ..
- Bifunctional T cell receptor based immunotherapeuticsHing C Wong; Fiscal Year: 2011..malignancies to evaluate the safety, immunogenicity, pharmacokinetic profile and to establish the maximum tolerated dose level (MTD)...
- Targeted Polymer Micelles for Treatment of Metastatic MelanomaKevin N Sill; Fiscal Year: 2013..Key experiments will include maximum tolerated dose, pharmacokinetics, biodistribution and efficacy...
- Dietary Supplement Selenium and HIF-1alpha Regulation in CancerSreenivasulu Chintala; Fiscal Year: 2010..additional chemo protective properties on healthy host tissues, allows dose escalation to higher than the maximum tolerated dose enabling to further enhance therapeutic efficacy...
- Hsp90 as a Target for the Treatment of Childhood CancerRochelle Bagatell; Fiscal Year: 2010..Primary objectives of the trial will be to establish the Dose Limiting Toxicity (DLT) and the Maximum Tolerated Dose (MTD) of 17-DMAG in these patients and to assess the extent to which the MTD of this drug alters the ..
- NF-KB and mTOR regulation in Waldenstrom MacroglobulinemiaIrene M Ghobrial; Fiscal Year: 2013..The clinical trial will include a Phase 1 study to determine the maximum tolerated dose (MTD) of the combination of AD001/rituximab and RAD001/rituximab/bortezomib...
- In vivo feasibility of a peripheral nerve imaging agentStephen B Kahl; Fiscal Year: 2013..We expect to use doses of rhNGF-NIR within the Maximum Tolerated Dose (MTD) established for rhNGF alone in clinical studies (0.1[unreadable]g/kg-0.3[unreadable]g/kg)...
- Novel Nanoparticle Therapy for Pancreatic CancerMark Kester; Fiscal Year: 2013..single molecule spectroscopy and 2) Determine pharmacokinetic parameters for targeted NPs including the maximum tolerated dose, biodistribution and bioavailability, and 3) Examine the safety and efficiency of target-specific loaded ..
- A NEW MECHANISM FOR TREATING OBESITYSalih J Wakil; Fiscal Year: 2012..To this end, we will carry out the following Tasks: Task 1: Evaluate maximum tolerated dose (MTD) by oral gavage of FGH-10019 to Sprague-Dawley rats...
- Conformal Total Body and Marrow Irradiation for LeukemiaSusanta K Hui; Fiscal Year: 2013..These advantages will make it possible to conduct clinical trials to determine a safe and efficacious maximum tolerated dose (MTD) of TBMI in the setting bone marrow transplant...
- Preclinical Studies on Polyunsaturated Fatty Acid-Taxoid Conjugate for IND FilingRAMESH CHANDER GUPTA; Fiscal Year: 2011..Pharmacokinetics/pharmacodynamics (PK/PD) studies including half-life, distribution, metabolism and maximum tolerated dose, as well as all other pre-clinical toxicology studies necessary for IND filing;(iii) optimization of the ..
- Clinical Development of 4-Cl-KYN to Treat PainRALPH SNODGRASS; Fiscal Year: 2010..studies in healthy human volunteers after single dose and repeated dosing of AV-101 to assess the maximum tolerated dose and the pharmacokinetic profiles of AV-101...
- Enhancing Use of Hydroxyurea In Sickle Cell Disease Using Patient NavigatorsWally R Smith; Fiscal Year: 2013..Secondary outcomes will include: four measures of adherence to HU;percent of patients achieving either maximum tolerated dose, a clinical endpoint, or maximum dose;ED and hospital visits;mean corpuscular volume;total hemoglobin;..
- Development of a novel agent for lung cancer preventionArun Kumar Sharma; Fiscal Year: 2013..We will use the experimental approach of determining the maximum tolerated dose (MTD) of dietary p-XS-Asp and evaluating its effectiveness for inhibiting tumor development in A/J mice ..
- Development of a New Diamine (SQ109) for the Treatment of C. difficile InfectionMARINA N PROTOPOPOVA; Fiscal Year: 2013..compounds identified in Aim 1 will be evaluated in additional studies, including determination of the maximum tolerated dose in mice, in vivo efficacy in animal models of infection, activity against intestinal flora (to evaluate ..
- Improving current therapies for myelomaDAN TOBY VOGL; Fiscal Year: 2013..therefore encompasses the following specific aims: (1) To determine, in a phase 1 clinical trial, the maximum tolerated dose of hydroxychloroquine when added to standard bortezomib therapy...
- Avoiding clearance to maximize dose: Shape, Flexibility, and a "Marker of Self"Dennis E Discher; Fiscal Year: 2013..anchorage of the smallest possible 'Marker of Self'polypeptide will open the dosage window on Maximum Tolerated Dose, enabling delivery of more drug (or oliogonucleotide) to a disease site such as a tumor or a dystrophic ..
- Macromolecular therapeutics for neoplastic meningitisMikhail I Papisov; Fiscal Year: 2011..investigate by PET how the conjugate distributes camptothecin in the leptomeningeal space, determine the maximum tolerated dose of the conjugate, and determine the efficacy of the conjugate in an established animal model of neoplastic ..
- Design, Syntheses and Studies of Novel Antituberculosis AgentsMarvin J Miller; Fiscal Year: 2013..We will also perform related studies, including gross toxicity, metabolism, pharmacokinetics (PK), maximum tolerated dose (MTD) and mode of action studies of new compounds with antiTB activity...
- Phase I Study of ALT-801 in Metastatic Melanoma/Kidney Cancer PatientsMayer Fishman; Fiscal Year: 2009..trial in patients with progressive metastatic malignancies to examine the dose limiting toxicity, maximum tolerated dose, pharmacokinetics and antitumor response of treatment with ALT-801;(2) expand the number of patients with ..
- Phase 1 Study of ABC294640 for the Treatment of Pancreatic CancerLynn W Maines; Fiscal Year: 2012..The primary objectives of the study will be to determine the maximum tolerated dose (MTD) and the dose limiting toxicities of ABC294640;to establish the dose of ABC294640 recommended for ..
- A Novel Therapy for the Treatment of Chest Wall Progression of Breast CancerGary S Rogers; Fiscal Year: 2010..are performance evaluation of the light delivery device used to deliver CLIPT therapy and determining the maximum tolerated dose (MTD) of light energy delivered over the 24 hour therapy...
- Long Acting Native GLP-1 formulations for Type 1 DiabetesElijah Bolotin; Fiscal Year: 2009..In Aim 2 the acute and chronic maximum tolerated dose of carrier and GLP-1 formulation will be determined in mice prior to the optimization of dosing planned in ..
- An inhaled PDGF receptor inhibitor for the treatment of pulmonary arterial hyperLawrence S Zisman; Fiscal Year: 2013..inhaler (MDI) or as a dry powder for inhalation delivery;2) Perform pharmacokinetic, pharmacodynamic, and maximum tolerated dose studies of the inhaled formulation...
- Development of transporter targeted platinum drugs for neuroblastomaRichard D Mamelok; Fiscal Year: 2012..In addition, the goal o this study is to identify a maximum tolerated dose (MTD), which is the highest dose that does not cause any measurable toxicity in the mice...
- LipoGels for Chelation of Transfusional Iron-OverloadM PANG XIONG; Fiscal Year: 2013..lipoGels for in vivo chelation of iron, 2) investigate the mechanism of iron chelation in vitro, and maximum tolerated dose, pharmacokinetics, and biocompatibility/safety of lipoGels in vivo, and 3) test the iron chelation ..
- Phase 1b Trial of stem cells in ALSSeward B Rutkove; Fiscal Year: 2013..This safety trial will employ progressive dose escalation to determine the maximum tolerated dose that can be used for the long term goal of performing Phase 2 and Phase 3 efficacy trials...
- Hydroxyurea Pharmacokinetics and PharmacogenomicsRussell E Ware; Fiscal Year: 2011..For example, the drug dosing is highly variable, with the maximum tolerated dose (MTD) for individual patients varying between 10 and 35 mg/kg/day...
- Phase I Study of Humanized 3F8 Monoclonal Antibody (Hu3F8) in Patients with High-Nai Kong V Cheung; Fiscal Year: 2012..The primary goal is to establish the maximum tolerated dose (MTD) with minimal/no pain side effects, and MTD with no dose-limiting toxicity (DLT)...
- Futility Study of Deferoxamine Mesylate in Intracerebral Hemorrhage (Hi-DEF)Magdy H Selim; Fiscal Year: 2013..double-blind, randomized, placebo-armed, phase-II, futility clinical study to determine if this maximum tolerated dose of DFO is of sufficient promise to improve outcome prior to embarking on a large-scale and costly phase ..
- An agent for the treatment of lung cancerDespina Komninou; Fiscal Year: 2012..2) Perform toxicity studies of PS. We will determine the genotoxicity, maximum tolerated dose and repeated dose/organ toxicity of PS...
- PHASE I CLINICAL TRIALS OF ANTICANCER AGENTSCharles Erlichman; Fiscal Year: 2013..or combinations of anticancer agents for the purposes of characterizing drug toxicity, determining the maximum tolerated dose, performing pharmacogenetic analysis, evaluating the pharmacokinetics, and relating clinical endpoints to ..
- Discovery and development of broad spectrum anti-flaviviral drugsTimothy A Haystead; Fiscal Year: 2013..mouse models of YFV and WNV infection and newly established models of DENV infection will be used for maximum tolerated dose and initial pharmacological and efficacy studies...
- Early Clinical Trials of New Anti-Cancer Agents with Phase I EmphasisEdward Chu; Fiscal Year: 2013..Determination of clinical toxicities and maximum tolerated dose (MTD) of an agent is no longer sufficient...
- Enteric-Coated Oral Beclomethasone Dipropionate in Patients with Acute EnteritisCHRISTOPHER JOSEPH SCHABER; Fiscal Year: 2010..Key endpoints being evaluated include, but are not limited to: 1. dose-limiting toxicity;2. maximum tolerated dose;3. incidence and severity of AEs probably related (i.e...
- Humanized Anti-Trop2-SN-38 Conjugate For Advanced Pancreatic CancerWilliam A Wegener; Fiscal Year: 2012..Thus, the goal of this Phase I application will be to complete a dose-escalation trial to determine the maximum tolerated dose or a biologically active dose of the hRS7 ADC in patients with stage III/IV pancreatic cancer who have ..
- Preclinical Evaluation of GluR2-3Y Peptide as a Potential New Medication for PolyYu Tian Wang; Fiscal Year: 2013..of the lead compound in an animal model of polydrug addiction;determination of minimum efficacy dose, maximum tolerated dose, therapeutic index, and optimal dose of the lead compounds;full pharmacokinetic and biodistribution ..
- Ginger for Chemoprevention of Colorectal CancerSuzanna Zick; Fiscal Year: 2009..these questions: (1) a Phase IA study to evaluate the single-dose pharmacokinetics, acute toxicity, and maximum tolerated dose (MTD) of ginger;(2) a study to examine the methods for effectively blinding study participants to ginger&..
- Investigation of a nanoparticle albumin-bound mTOR inhibitor, nab-rapamycin for tNeil Desai; Fiscal Year: 2013..Our specific aims are: Phase I portion - (1) in a clinical phase 1 study, establish safety and maximum tolerated dose of intravesical nab-rapamycin, (2) in a genetically engineered mouse bladder cancer model, evaluate ..
- Small Molecule Modulators of the Glutamate Transporter for Treatment of ALSMarcie A Glicksman; Fiscal Year: 2012..Pharmacokinetic studies have been completed and acute and chronic maximum tolerated dose studies are in progress to help drive additional medicinal chemistry efforts.
- iNOS/Akt Inhibotor for Colon Cancer ChemopreventionDHIMANT HARKISAN DESAI; Fiscal Year: 2010..We specifically propose to investigate the pharmacokinetics, pharmacodynamics, tissue distribution, and in vivo maximum tolerated dose (MTD) of PBISe administered by intravenous injection or diet in male F344 rat model.
- Gene Modified Dendritic Cell Therapy in Lung CancerJay M Lee; Fiscal Year: 2013..The objectives of the study are 1) to determine the safety and maximum tolerated dose (MTD) of Ad-CCL-21-DC, 2) to determine the local and systemic biologic activity (i.e...
- Phase 1/2 of AT-101 With Lenalidomide for Tx of Chronic Lymphocytic LeukemiaAsher A Chanan-Khan; Fiscal Year: 2012..This Phase 2/3 clinical trial is proposed to determine the maximum tolerated dose (MTD), to determine the efficacy of the lenalidomide/AT-101 combination, and to test this hypothesis in ..
- Mitigation of Radiation-Induced Pulmonary Injury with Nrf2 activatorZeljko Vujaskovic; Fiscal Year: 2013..Specifically, the studies are designed to determine the maximum tolerated dose (MTD), tissue and plasma PK, establish a pharmacodynamics assay based on the mechanism of the compound, ..
- Targeting RAS signaling with CDK and AKT inhibition in pancreatic cancerNilofer Azad; Fiscal Year: 2013..The first cohort of this study will be to determine the maximum tolerated dose (MTD) and the safety and toxicity profiles for this combination in pancreatic cancer...
- Medical Physics Training Grant for Image-Guided Therapy ResearchEdward F Jackson; Fiscal Year: 2010..for such physiological imaging techniques to order to establish optimal biologic dose, rather than maximum tolerated dose, in clinical trials of cytostatic agents, e.g., antiangiogenic/antivascular drugs...
- Combined radio- and immunotherapy of aggressive NHLWilliam A Wegener; Fiscal Year: 2013..90Y-epratuzumab (humanized anti-CD22 IgG) and veltuzumab (humanized anti-CD20 IgG) have established the maximum tolerated dose (MTD) of a fractionated injection of 90Y-epratuzumab, and the optimal biological dose of veltuzumab, with ..
- PHARMACOLOGY AND EFFICACY OF NOVEL TAXOL FORMULATIONSROBERT STRAUBINGER; Fiscal Year: 1999..Delayed toxicity likewise is reduced, with a 2-7-fold increase in Maximum Tolerated Dose (MTD) for T-lip...
- Anaerobic Bacteria as Oncopathic Agents for Pancreatic CancerSavio Woo; Fiscal Year: 2009..The maximum tolerated dose of this knock-out strain (Cp/plc-/sod-) was elevated by one-log over that of Cp/plc- in tumor-bearing mice...
- Fatty Acid Synthase Inhibitors: Ovarian Cancer TherapyALBERT OWENS; Fiscal Year: 2007..against the multidrug resistant ovarian cancer-derived cell line OVCAR-3; 3) a determination of the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) in BALB/C mice on low and high fat diets; and, 4) efficacy studies ..
- Development of a T cell specific multiple sclerosis drugArthur Vandenbark; Fiscal Year: 2005..I human clinical studies; 2) conclude pre-clinical safety studies, including maximum non-effective dose, maximum tolerated dose, and repeat dose toxicity studies; and 3) conduct Phase I clinical trials in accordance with FDA and NIH ..
- Evaluation of CYP24 as a Target for Enhancing Vitamin D*Donald Trump; Fiscal Year: 2006..5mg BID) in patients with advanced cancer to determine the (a) maximum tolerated dose (MTD) of oral calcitriol + ketoconazole/Dex (b) pharmacokinetics of calcitriol +/- ketoconazole/dex (c) ..
- NEW BCAS FOR RADIOIMMUNOTHERAPY WITH RADIOMETALSDonald Buchsbaum; Fiscal Year: 2001..colon cancer nodules compared to blood, and to determine the relative tumor efficacy at the maximum tolerated dose of 188Re-HuCC49ACH2 VS. 188Re-HuCC49...
- Modulating the tumor micro-environment in CLL using flavopiridol and lenalidomideKristie Blum; Fiscal Year: 2009..trial of flavopiridol and lenalidomide to determine the specific toxicities, dose limiting toxicity (DLT), maximum tolerated dose (MTD), and preliminary efficacy of this combination in patients with previously treated B-cell CLL, ..
- Rhenium-188 therapy of NIS-expressing breast tumorsEkaterina Dadachova; Fiscal Year: 2003..188-Re and 131-I therapy of xenografted breast tumors in nude mice including dose escalation and maximum tolerated dose determination...
- RACIVIR FOR TREATMENT OF HEPATITIS B AND HIV INFECTIONSMichael Otto; Fiscal Year: 2000..We wish to determine the maximum tolerated dose (MTD) of Racivir compared to (+)-FTC and establish a rationale, based on the safety profile, for ..
- Phase I / II Trial for Neutron Capture TherapyMatthew Palmer; Fiscal Year: 2002..This phase I/II trial is designed to determine the maximum tolerated dose (MTD) for cranial NCT irradiation, an important parameter for future clinical trials...
- IMPROVED SECOND ANTIBODY RADIOIMMUNOTHERAPY OF CANCERROBERT SHARKEY; Fiscal Year: 2000..testing is planned to test the hypothesis that this procedure will permit a substantial increase in the maximum tolerated dose (MTD) in patients, and provide higher radiation doses to tumors...
- DNA Repair Inhibition and Cancer TherapyJOHN HEARST; Fiscal Year: 2003..effects that can limit the effectiveness of the therapy because the clinician must avoid exceeding the maximum tolerated dose (MTD)...
- Phase I Trial of 90Y Octreotide in Childhood Solid TumorM O DORISIO; Fiscal Year: 2002..The Specific Aims are: I. Conduct a Phase I trial to determine the maximum tolerated dose of 90Y-DOTA-tyr3-Octreotide in children with refractory neuroblastoma, medulloblastoma, and other ..
- Targeting Androgen -IGF Interactions in Prostate CancerCharles Ryan; Fiscal Year: 2009..appears safe in preclinical models, a phase I study in relapsed prostate cancer patients to determine the maximum tolerated dose (MTD) and PSA modulating effects after 28 days of treatment is planned...
- TREATMENT OF MALIGNANT PLEURAL EFFUSIONSRoman Perez Soler; Fiscal Year: 1993..The objectives of the study are: 1) to determine the maximum tolerated dose, spectrum of toxicity, and antitumor efficacy of L-NDDP administered into the pleural space in patients ..
- COMBINED RADIOIMMUNOTHERAPY & CHEMOTHERAPY--COLON CANCERMalik Juweid; Fiscal Year: 1999..The dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of combined RAIT and 5-FU-LV has therefore, to be established experimentally, before it can be used ..