Abstract:
:A novel schedule of 5-fluorouracil administration has been developed for biochemical modulation studies. In combination with the pyrimidine synthesis inhibitor PALA, 5-fluorouracil has been given as a 24-hour infusion, repeated weekly: a dose of 2600 mg/m2 is well tolerated. To identify a suitable dose of 5-fluorouracil as a single agent on this schedule, we treated 26 patients at doses ranging from 2800 to 3400 mg/m2 per week. Two-thirds of the patients had failed previous therapy, and most were symptomatic from their disease. Over half of the patients had metastatic colorectal cancer. The dose-limiting toxicity was diarrhea: Grade 3 or 4 toxicity occurred at every level tested. Twenty-two of the 26 patients required therapy interruption because of toxicity. The severity of this toxicity indicated that escalation of 5-fluorouracil on this schedule beyond the 2600 mg/m2 known to be tolerated in the PALA-containing regimen, would be impractical. Two patients, both with previously untreated colorectal cancer, had partial remissions lasting three and five months respectively. This dose-intense schedule of 5-fluorouracil administration will be explored further in large-scale randomized trials.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Haas NB,Hines JB,Hudes GR,Johnston N,Ozols RF,O'Dwyer PJdoi
10.1007/BF00874152subject
Has Abstractpub_date
1993-05-01 00:00:00pages
181-5issue
2-3eissn
0167-6997issn
1573-0646journal_volume
11pub_type
临床试验,杂志文章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
pub_type: 杂志文章
doi:10.1007/BF00874426
更新日期:1993-11-01 00:00:00
abstract::An in vitro assay, which evaluates drug effect on 3H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activiti...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175294
更新日期:1987-01-01 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
pub_type: 杂志文章,评审
doi:10.1007/BF00173679
更新日期:1996-01-01 00:00:00
abstract::The purpose of this study was to assess the efficacy and safety of bevacizumab plus cetuximab with or without gemcitabine in patients with advanced pancreatic adenocarcinoma. Patients with locally advanced or metastatic pancreatic adenocarcinoma, previously untreated, were randomized to bevacizumab (10 mg/kg q2w) plus...
journal_title:Investigational new drugs
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10637-011-9691-8
更新日期:2012-08-01 00:00:00
abstract::There is no effective systemic therapy for disseminated metastatic melanoma. Data suggest that endothelin may play a role in pathophysiology of melanoma and that the dual endothelin receptor antagonist bosentan may have anti-tumor activity. This multicenter, open-label, single-arm, prospective, proof-of-concept study ...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-006-9014-7
更新日期:2007-06-01 00:00:00
abstract:BACKGROUND:This study investigated the activity of MK-2206, an AKT inhibitor, in metastatic or recurrent nasopharyngeal carcinoma (NPC). METHOD:Oral MK-2206 at a dose of 200 mg was administered on days 1, 8, 15 and 22 of a 28-day cycle until progression. Plasma EBV DNA clearance during the first month of treatment was...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-015-0264-0
更新日期:2015-08-01 00:00:00
abstract::N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) follo...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00180821
更新日期:1996-01-01 00:00:00
abstract::Didemnin B is a depsipeptide derived from a Caribbean tunicate (sea squirt) that has demonstrated antineoplastic activity against a variety of murine tumor models, including the L1210 and P388 leukemia, the B16 melanoma, and M5076 sarcoma cell lines. Based on these data, we designed a phase II trial in which 15 patien...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00877248
更新日期:1992-08-01 00:00:00
abstract::Angiogenesis is recognized as an important biological process that allows growth of a tumor beyond an initial small size. PTK787/ZK222584, a potent orally active angiogenesis inhibitor capable of inhibiting all known isoforms of Vascular Endothelial Growth Factor (VEGF) receptor, belongs to the class of aminophthalazi...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9157-9
更新日期:2009-02-01 00:00:00
abstract::Background High-risk neuroblastoma has poor outcomes with high rates of relapse despite aggressive treatment, and novel therapies are needed to improve these outcomes. Ponatinib is a multi-tyrosine kinase inhibitor that targets many pathways implicated in neuroblastoma pathogenesis. We hypothesized that ponatinib woul...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-016-0387-y
更新日期:2016-12-01 00:00:00
abstract::Aims A primary objective of this study was to investigate the effect of single and multiple doses of alisertib, an investigational Aurora A kinase inhibitor, on the QTc interval in patients with advanced malignancies. The dose regimen used was the maximum tolerated dose which was also the recommended phase 3 dose (50 ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0498-0
更新日期:2018-04-01 00:00:00
abstract:PURPOSE:BMS-275183 is an oral C-4 methyl carbonate analogue of paclitaxel that has the same mechanism of action, stabilization of tubulin polymerization. The present study was designed to: (i) assess the safety and tolerability of BMS-275183, and (ii) determine a suitable Phase II dose of BMS-275183 when given on a con...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-010-9498-z
更新日期:2011-12-01 00:00:00
abstract::Over forty papers describing correlations between in vitro human tumor sensitivity to a variety of chemotherapeutic agents and the in vivo response of patients to those agents have been published since the publication in 1978 by Salmon and Hamburger of their results of a human tumor colony-forming chemosensitivity ass...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/BF00173788
更新日期:1984-01-01 00:00:00
abstract::Seventeen patients with small cell lung cancer entered a phase II trial testing the feasibility of adding high dose epirubicin (100-120 mg/m2, day 1) in combination with etoposide (60-80 mg/m2, days 1-5) and cisplatin (70 mg/m2, day 1) courses repeated every three weeks. Complete responders received thoracic (40 Gy) a...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00873130
更新日期:1992-07-01 00:00:00
abstract::Survivin is expressed in tumor cells, including acute myeloid leukemia (AML), regulates mitosis, and prevents tumor cell death. The antisense oligonucleotide sodium LY2181308 (LY2181308) inhibits survivin expression and may cause cell cycle arrest and restore apoptosis in AML. In this study, the safety, pharmacokineti...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s10637-013-9935-x
更新日期:2013-08-01 00:00:00
abstract::Fifteen patients with advanced, cisplatin-refractory germ cell tumors (GCT) were treated on a phase II trial with topotecan. None of the 14 evaluable patients achieved a complete or partial response. Myelosuppression was the major toxicity. The median nadir leukocyte count was 1.75 cells/mm3, neutrophil count was 1.55...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00872866
更新日期:1995-01-01 00:00:00
abstract:INTRODUCTION:Continuous efforts from scientists of diverse fields are necessary not only to better understand the mechanism by which multidrug resistant (MDR) cancer cells occur, but also to boost the discovery of new cytotoxic compounds. This work was designed to assess the cytotoxicity and the mechanism of action of ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-014-0137-y
更新日期:2014-12-01 00:00:00
abstract:PURPOSE:Combining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested uti...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9766-6
更新日期:2012-12-01 00:00:00
abstract::Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression through their effects on the compact chromatin structure. In clinical studies, several classes of histone deacetylase inhibitors (HDACi) have demonstrated potent anticancer activities with metal complexes. Hence, we syn...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0489-1
更新日期:2017-12-01 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
pub_type: 临床试验,杂志文章
doi:10.1023/a:1016066529642
更新日期:1998-01-01 00:00:00
abstract::Herein we describe a series of multifunctional 5-aminolevulinic-acid (ALA) prodrugs for photodynamic dependent and independent cancer therapy (PDT). We studied the cell-death mechanisms in glioblastoma U251 cells treated with four ALA-prodrugs: (1) AlaAcBu, that releases ALA, acetaldehyde, and butyric acid; (2) AlaFaB...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9669-6
更新日期:2012-06-01 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
pub_type: 杂志文章
doi:10.1023/a:1026299118067
更新日期:2003-11-01 00:00:00
abstract::Interleukin-4 (IL-4) is a pleiotropic cytokine affecting growth and differentiation of various cell types as well as regulating other cytokines. To study the effect of IL-4 on AIDS-related Kaposi's sarcoma (AIDS-KS) cells, we first examined the tumor cells for IL-4 receptor (IL-4R) expression. KS cells express a singl...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/a:1005958123893
更新日期:1997-01-01 00:00:00
abstract::Thirty-two patients with advanced epidermoid carcinoma of the esophagus were treated with ifosfamide (1.50 gm/m2 daily x 5 days) with uroprotective mesna in a phase II study. Eighteen patients were previously untreated. Of 28 evaluable patients, two (7%) had partial remissions lasting 2+ and 6+ months. Toxicity was pr...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175406
更新日期:1988-09-01 00:00:00
abstract::Anthracycline antibiotics (ANT), such as doxorubicin or daunorubicin, are a class of anticancer drugs that are widely used in oncology. Although highly effective in cancer therapy, their usefulness is greatly limited by their cardiotoxicity. Possible mechanisms of ANT cardiotoxicity include their conversion to seconda...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/s10637-017-0443-2
更新日期:2017-06-01 00:00:00
abstract::Hexamethylenebisacetamide (HMBA), an in vitro differentiating agent, was studied for its pharmacodynamic actions in animals. Plasma stability, organ distribution, excretion, oral bioavailability, and estimates of pharmacokinetic parameters and acute lethality were determined in rats. The single dose intraperitoneal LD...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00179430
更新日期:1985-01-01 00:00:00
abstract::In this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m2 i.v. followed one day later with mitoxantrone (Novantrone; dihydroxyanthracenedione) 16 mg/m2 i.v. Drug treatment was repeated every 3-4 weeks, for a maximum of 12 cycles. The overall response rate w...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00174165
更新日期:1985-01-01 00:00:00
abstract::Major discrepancies concerning risk-benefit assessments and regulatory actions are frequent among regulatory agencies. We explored the differences by scrutinizing a case of gemtuzumab ozogamicin (GO) in patients with acute myeloid leukaemia (AML). Assessment reports of GO were retrieved form the websites of the US Foo...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/s10637-012-9877-8
更新日期:2013-04-01 00:00:00
abstract::Aberrant activation of the Wnt/β-catenin signaling pathway promotes osteosarcoma tumorigenesis and metastasis. In this study, we tested the hypothesis that osteosarcoma progression may be delayed by disrupting the Wnt/β-catenin pathway using small molecule inhibitors such as curcumin and PKF118-310. Effective inhibiti...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9311-z
更新日期:2010-12-01 00:00:00
abstract::This dose-escalating phase I clinical trial was designed to determine the recommended dose (RD) and to assess the safety and feasibility of weekly plitidepsin (1-hour i.v. infusion, Days 1, 8 and 15) combined with carboplatin (1-hour i.v. infusion, Day 1, after plitidepsin) in 4-week (q4wk) cycles given to patients wi...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9488-1
更新日期:2011-12-01 00:00:00