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 assay (CFCA). The true positive rate in over 1600 correlations is 71% and the true negative rate is 94%. The biological elements of the assay, its developmental history, its place in the spectrum of in vitro chemosensitivity assays, and its theoretical and practical limitations are discussed. The scope, design, and limitations of key clinical trials are presented and an analysis of the potential errors of statistical interpretation of the trials as well as the results of the trials is given.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Bradley EC,Issell BF,Hellman Rdoi
10.1007/BF00173788subject
Has Abstractpub_date
1984-01-01 00:00:00pages
59-70issue
1eissn
0167-6997issn
1573-0646journal_volume
2pub_type
杂志文章,评审abstract：AIM:5,6-Dimethylxanthenone-4-acetic acid (DMXAA) (ASA404), a low molecular weight antivascular drug currently in clinical trial, acts both directly on the tumour vascular endothelium and indirectly through the induction of inflammatory cytokines and other vasoactive molecules from macrophages and other host cells. We w...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-008-9167-7
更新日期：2009-06-01 00:00:00
abstract：:Background Older non-small cell lung cancer (NSCLC) patients under erlotinib are reported to experience more acute toxicity. We hypothesized that modifications in erlotinib pharmacokinetics might explain this observation. Methods A monocentric prospective clinico-pharmacological study included stage IIIb/IV NSCLC cons...
journal_title：Investigational new drugs
pub_type： 临床试验,杂志文章
doi：10.1007/s10637-016-0400-5
更新日期：2017-04-01 00:00:00
abstract：PURPOSE:This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. EXPERIMENTAL DESIGN:This was an open-label, multicenter, dose-escalation stu...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-012-9815-9
更新日期：2013-02-01 00:00:00
abstract：:Human topoisomerase II (hTopoII) inhibitors are important chemotherapeutic agents in many different settings including treatment of malignant mesothelioma. Topoisomerase poisons, such as etoposide and doxorubicin, function by trapping the DNA-enzyme covalent complex producing DNA strand breaks which can ultimately lea...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-011-9720-7
更新日期：2012-08-01 00:00:00
abstract：BACKGROUND:Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a...
journal_title：Investigational new drugs
pub_type： 临床试验,杂志文章
doi：10.1007/BF00874443
更新日期：1994-01-01 00:00:00
abstract：:Chemoprevention opens new perspectives in the prevention of cancer and other degenerative diseases. Use of target-organ biological models at the histological and genetic levels can markedly facilitate the identification of potential chemopreventive agents. Our aim was to study the chemopreventive efficacy of pronyl-ly...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-008-9122-7
更新日期：2008-12-01 00:00:00
abstract：:Androgen receptors are present in both pancreatic cancer tissue and cell lines. Flutamide is a potent antiandrogen widely used in clinical practice for patients with metastatic prostate cancer. This Phase II trial was undertaken to evaluate the impact of flutamide in patients with advanced pancreatic adenocarcinoma wh...
journal_title：Investigational new drugs
pub_type： 临床试验,杂志文章
doi：10.1023/a:1005989519350
更新日期：1997-01-01 00:00:00
abstract：PURPOSE:Erlotinib (Tarceva®, OSI-774) is a small molecule inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. As high-grade gliomas frequently show amplification, overexpression and/or mutation of EGFR, this drug has been tested in several clinical trials with glioblastoma patients, but unfortunat...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-010-9569-1
更新日期：2012-04-01 00:00:00
abstract：:This report shows that N-acylation of the protein kinase C (PKC) substrate Arg-Lys-Arg-Thr-Leu-Arg-Arg-Leu (RKRTLRRL) provides it with a potent inhibitory activity against PKC. N-myristoyl-RKRTLRRL inhibited Ca2(+)- and phosphatidylserine (PS)-dependent histone phosphorylation catalyzed by PKC with a 50% inhibitory co...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00175084
更新日期：1991-05-01 00:00:00
abstract：:Fifty-four evaluable patients with SCLC previously treated with chemotherapy received either N-methylformamide or spirogermanium. There was one partial response to N-methylformamide. The median survival times for patients treated with N-MF and spirogermanium were 11.7 and 12.6 weeks respectively. Five patients treated...
journal_title：Investigational new drugs
pub_type： 临床试验,杂志文章
doi：10.1007/BF00177255
更新日期：1990-05-01 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
pub_type： 杂志文章,评审
doi：10.1023/a:1006383831045
更新日期：2000-02-01 00:00:00
abstract：:Recent clinical trials carried out in patients with advanced cancer have shown that recombinant TRAIL administration is usually safe and well tolerated when used either alone or in association with chemotherapeutic drugs. Notably, anticancer chemotherapy can be associated to cardiomiopathy. We have here demonstrated t...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-010-9627-8
更新日期：2012-06-01 00:00:00
abstract：:Breast cancer is commonly treated with anti-estrogens or aromatase inhibitors, but resistant disease eventually develops and new therapies for such resistance are of great interest. We have previously isolated several tamoxifen-resistant variant sub-lines of the MCF-7 breast cancer cell line and provided evidence that...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-011-9768-4
更新日期：2012-12-01 00:00:00
abstract：:Colon cancer is the third most malignant neoplasm in the world and it remains today an important cause of death, especially in western countries. In this study, we have evaluated the chemopreventive efficacy of morin on tissue lipid peroxidation and antioxidant status, which are used as biomarkers in 1,2-dimethylhydra...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-008-9136-1
更新日期：2009-02-01 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
pub_type： 杂志文章
doi：10.1007/s10637-005-3690-6
更新日期：2006-05-01 00:00:00
abstract：:Peloruside A is a microtubule-stabilizing agent that is currently under investigation as a potential anticancer agent. Peloruside A binds to a site on β-tubulin that is distinct to that of the taxanes (paclitaxel and docetaxel) and the epothilones. An attractive clinical quality of microtubule-stabilizing agents is th...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-015-0232-8
更新日期：2015-06-01 00:00:00
abstract：:Background MET is a tyrosine kinase receptor involved in the regulation of cell proliferation and migration. Reported here are the phase I dose-escalation results for LY2875358, a monoclonal antibody against MET, in Japanese patients with advanced malignancies. Methods The study comprised a 3 + 3 dose-escalation part ...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-016-0370-7
更新日期：2016-10-01 00:00:00
abstract：:Topotecan (NSC 609099) is a camptothecin analogue that demonstrated activity against a variety of human tumors in preclinical studies. A phase II trial was performed with topotecan given to patients with locally advanced or metastatic adenocarcinoma of the stomach. Topotecan was administered IV Bolus over 30 minutes o...
journal_title：Investigational new drugs
pub_type： 临床试验,杂志文章
doi：10.1023/a:1005899720463
更新日期：1997-01-01 00:00:00
abstract：:Glioblastoma (GBM), one of the most malignant human neoplasias, responds poorly to current treatment modalities, with temozolomide (TMZ) being the drug most frequently used for its treatment. Tetra-O-methyl Nordihydroguaiaretic Acid (M4N) is a global transcriptional repressor of genes dependent on the Sp1 transcriptio...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-012-9917-4
更新日期：2013-08-01 00:00:00
abstract：:Background It would be useful to have criteria for predicting long-term treatment responses to immune checkpoint inhibitors (ICIs). Maximum depth of response correlates with treatment outcomes among patients receiving programmed death protein 1 axis inhibitors for non-small cell lung cancer (NSCLC). We investigated as...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-019-00770-y
更新日期：2019-12-01 00:00:00
abstract：:Nafazatrom, a synthetic pyrazolinone derivative, has been shown to have substantial antitumor activity in vitro and antitumor and antimetastatic activity in experimental animal systems. The drug has produced no substantial toxicity in preclinical studies and during limited human trials. A phase I clinical trial with t...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00179592
更新日期：1986-01-01 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 study was designed to test the hypothesis that specific inhibition of cathepsins B and L will cause death of neuroblastoma cells. Five compounds that differ in mode and rate of inhibition of these two enzymes were all shown to cause neuroblastoma cell death. Efficacy of the different compounds was related to thei...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-012-9826-6
更新日期：2013-02-01 00:00:00
abstract：BACKGROUND:Gemcitabine (G) has shown activity in mantle cell lymphoma (MCL) as a single agent. The combination of mitoxantrone (M) and rituximab (R) is also active in MCL. The primary objective of this study was to determine the efficacy of G+M+R in relapsed or refractory MCL. PATIENTS AND METHODS:Sixteen patients wer...
journal_title：Investigational new drugs
pub_type： 杂志文章,多中心研究
doi：10.1007/s10637-008-9191-7
更新日期：2009-10-01 00:00:00
abstract：:Echinomycin is a quinoxaline antibiotic that was originally isolated from Streptomyces echinatus. Based on its antitumor activity against two i.p. implanted murine tumors, the B16 melanoma, and the P388 leukemia, it was brought into clinical trials by the National Cancer Institute. Recent studies on its cytotoxic acti...
journal_title：Investigational new drugs
pub_type： 临床试验,杂志文章,评审
doi：10.1007/BF00170766
更新日期：1985-01-01 00:00:00
abstract：:Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic melanoma and other cancers and have shown promising results. Inhibition of CTLA-4 characteristically induces well-known side effects called "immune-related adverse ...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-014-0092-7
更新日期：2014-08-01 00:00:00
abstract：PURPOSE:The transcription factor nuclear factor-kB (NFkB) is implicated in gastric cancer carcinogenesis and survival, and its inhibition by proteosome inhibition is associated with preclinical gastric cancer anti-tumor activity. We examined the single agent efficacy of bortezomib, a selective proteasome inhibitor, in ...
journal_title：Investigational new drugs
pub_type： 杂志文章,多中心研究
doi：10.1007/s10637-010-9474-7
更新日期：2011-12-01 00:00:00
abstract：:Taxol was administered as a 24-hour continuous infusion at 250 mg/m2 in this Phase II trial in patients with adenocarcinomas of the upper gastrointestinal tract (UGIT). Twenty-five patients were entered between July 1991 and June 1992, twenty-three were eligible and were evaluated for toxicity and twenty-two were asse...
journal_title：Investigational new drugs
pub_type： 临床试验,杂志文章
doi：10.1007/BF00873804
更新日期：1995-01-01 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：:Cancer is one of the major causes of death for non-transmissible chronic diseases worldwide. Conventional treatments including surgery, chemotherapy and external beam radiotherapy are generally far from curative. Complementary therapies are attempted for achieving more successful treatment response. Systemic targeted ...
journal_title：Investigational new drugs
pub_type： 杂志文章,评审
doi：10.1007/s10637-011-9758-6
更新日期：2012-10-01 00:00:00
