Abstract:
PURPOSE:We report on a statistical method for grouping anti-cancer drugs (GRAD) in single mouse trials (SMT). The method assigns candidate drugs into groups that inhibit or do not inhibit tumor growth in patient-derived xenografts (PDX). It determines the statistical significance of the group assignments without replicate trials of each drug. METHODS:The GRAD method applies a longitudinal finite mixture model, implemented in the statistical package PROC TRAJ, to analyze a mixture of tumor growth curves for portions of the same tumor in different mice, each single mouse exposed to a different drug. Each drug is classified into an inhibitory or non-inhibitory group. There are several advantages to the GRAD method for SMT. It determines that probability that the grouping is correct, uses the entire longitudinal tumor growth curve data for each drug treatment, can fit different shape growth curves, accounts for missing growth curve data, and accommodates growth curves of different time periods. RESULTS:We analyzed data for 22 drugs for 18 human colorectal tumors provided by researchers in a previous publication. The GRAD method identified 18 drugs that were inhibitory against at least one tumor, and 10 tumors for which there was at least one inhibitory drug. Analysis of simulated data indicated that the GRAD method has a sensitivity of 84% and a specificity of 98%. CONCLUSION:A statistical method, GRAD, can group anti-cancer drugs into those that are inhibitory and those that are non-inhibitory in single mouse trials and provide probabilities that the grouping is correct.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Gordon D,Axelrod DEdoi
10.1007/s00280-019-03942-ysubject
Has Abstractpub_date
2019-12-01 00:00:00pages
1167-1178issue
6eissn
0344-5704issn
1432-0843pii
10.1007/s00280-019-03942-yjournal_volume
84pub_type
杂志文章abstract:PURPOSE:To assess the effect of elotuzumab on corrected QT (QTc) intervals and cardiac safety. METHODS:Patients with high-risk smoldering multiple myeloma who had been treated with elotuzumab monotherapy (10 or 20 mg/kg) in Study CA204011 (NCT01441973) underwent electrocardiogram (ECG) examination over 8-10 weeks (tre...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3182-8
更新日期:2016-12-01 00:00:00
abstract::A three-compartment model was fitted to idarubicin data in a NONMEM pooled-data approach. Clearance (CL) of 221.7 ml/min was relatively high, and drug distribution was rapid (CLD = 248.3 ml/min) and extensive [steady-state volume of distribution (Vss) 24 1]. The area under the concentration-time curve (AUC) of idarbic...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050614
更新日期:1997-01-01 00:00:00
abstract::Previous studies of irinotecan pharmacogenetics have shown that the UGT1A1*28 polymorphism has an effect on irinotecan (IRI)-induced toxicities in Caucasians. Yet compared with the UGT1A1*6 mutation, the UGT1A1*28 occurs at a much lower frequency in the Asians. Whether UGT1A1*6 and UGT1A1*28 are associated with IRI-in...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00280-017-3306-9
更新日期:2017-06-01 00:00:00
abstract::Cytidine analogues such as cytosine arabinoside, gemcitabine, decitabine, 5-azacytidine, 5-fluoro-2'-deoxycytidine and 5-chloro-2'-deoxycytidine undergo rapid catabolism by cytidine deaminase (CD). 3,4,5,6-tetrahydrouridine (THU) is a potent CD inhibitor that has been applied preclinically and clinically as a modulato...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0625-2
更新日期:2008-08-01 00:00:00
abstract::Our previous randomised trial in patients with advanced ovarian cancer indicated a significant response and survival advantage for those receiving high-dose (100 mg/m2) as compared with low-dose (50 mg/m2) cisplatin in combination with cyclophosphamide (750 mg/m2). However, this was accompanied by more toxicity; perip...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s002800050723
更新日期:1998-01-01 00:00:00
abstract:PURPOSE:Based on our mouse xenograft model demonstrating that intermittent high-dose gefitinib sensitizes tumors to subsequent treatment with taxanes, we initiated this phase I trial to explore docetaxel in combination with escalating doses of intermittent gefitinib (Iressa) given prior to docetaxel. METHODS:This was ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0286-6
更新日期:2007-03-01 00:00:00
abstract::The pharmakokinetic profiles of intraperitoneally infused platinum analogues were determined in 13 women exhibiting minimal residual disease following surgery and systemic chemotherapy for epithelial ovarian cancer or fallopian tube carcinoma by following the disposition of tracer doses of 195mPt radiolabel. Six patie...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685543
更新日期:1991-01-01 00:00:00
abstract:BACKGROUND:Metastatic bladder cancer is a serious condition with a 5-year survival rate of approximately 14 %, a rate that has remained unchanged for almost three decades. Thus, there is a profound need to identify the driving mutations for these aggressive tumors to better determine appropriate treatments. Mutational ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2376-1
更新日期:2014-03-01 00:00:00
abstract:PURPOSE:To explore the clinical significance of plasma D-dimer increase for transcatheter arterial chemoembolization (TACE) in patients with primary liver cancer (PLC). METHODS:The clinical data of 80 PLC patients who underwent TACE in our hospital from January 2015 to January 2017 were collected, including the plasma...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03778-6
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:Bevacizumab is approved for various cancers. This analysis aimed to comprehensively evaluate bevacizumab pharmacokinetics and the influence of patient variables on bevacizumab pharmacokinetics. METHODS:Rich and sparse bevacizumab serum concentrations were collected from Phase I through IV studies in early a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3079-6
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND:Few clinical phase II studies using non-platinum doublet as adjuvant chemotherapy following complete resection of non-small-cell lung cancer (NSCLC) have been published, so this clinical study was designed to evaluate the toxicity profile and efficacy of the non-platinum doublet of docetaxel (DOC) + gemcitab...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0391-6
更新日期:2007-09-01 00:00:00
abstract::Bizelesin (U-77779) is a highly potent bis-alkylating antitumor agent that is effective against several tumor systems in vitro and in vivo. V79 cells that were 125- to 250-fold resistant to bizelesin developed after constant exposure to gradually increasing concentrations of the drug. Resistant cells exhibited a multi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686110
更新日期:1994-01-01 00:00:00
abstract::In recent years significant progress in the understanding of the immune biology of melanoma has evolved from the identification of melanoma antigens (MAs) recognized by T cells. MAs consist of intracellular proteins that are expressed on the surface of cancer cells in association with human leukocyte antigen (HLA) cla...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/pl00014052
更新日期:2000-01-01 00:00:00
abstract::Some of 66 patients with head and neck tumors were treated with high-dose methotrexate monochemotherapy. The use of a prospective mathematical model with pharmacokinetic surveillance proved to be reliable, practical, and useful. By this means chemotherapy could be individualized, with a resultant marked reduction in t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257744
更新日期:1982-01-01 00:00:00
abstract:PURPOSE:The antifolate pralatrexate (10-propargyl-10-deazaaminopterin, PDX) demonstrates greater in vitro and in vivo antitumor efficacy than methotrexate. Preclinical models indicated that the efficacy of pralatrexate may be enhanced by coadministration with probenecid. The aim of this phase I study was to determine t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0080-x
更新日期:2006-05-01 00:00:00
abstract::Deoxycoformycin (dCF) is a promising new antineoplastic agent in the treatment of lymphoid malignancies, particularly hairy cell leukemia (HCL). Skin toxicity in the form of a maculopapular eruption has previously been reported but has not clearly been associated with idiosyncratic reactions. We present five cases of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00267950
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:To evaluate the efficacy and safety of irinotecan as second-line treatment in patients with advanced colorectal cancer (ACC) failing or relapsing after 5-fluorouracil (5-FU) plus leucovorin (LV) standard chemotherapy. PATIENTS AND METHODS:Irinotecan was randomly administered in two different schedules (once ev...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00280-003-0659-z
更新日期:2003-12-01 00:00:00
abstract:PURPOSE:The objectives of this phase I dose-finding study of erlotinib were to investigate the toxicity profile, to confirm the acceptable toxicity of doses up to 150 mg/day, and to assess the pharmacokinetic (PK) profile and antitumor activity in Japanese patients with solid tumors. PATIENTS AND METHODS:Patients with...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0494-8
更新日期:2008-03-01 00:00:00
abstract:PURPOSE:Tomudex is a second-generation folate analogue that when polyglutamated is a potent inhibitor of thymidylate synthase (TS). METHODS:Based on indications of antitumor activity in phase I trials, the Gynecologic Oncology Group initiated a phase II study of Tomudex 3 mg/m2 intravenously every 3 weeks in patients ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050786
更新日期:1998-01-01 00:00:00
abstract::The nephrotoxic interaction between cis-diamminedichloroplatinum (CDDP) and amikacin (AMI) was studied in rats. Following a single dose of CDDP (5 mg/kg i.v.), AMI (60 mg/kg s.c.) was given for 14 days. When given alone CDDP caused a 40% fall in the glomerular filtration rate (GFR), whereas AMI alone had no effect on ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257319
更新日期:1988-01-01 00:00:00
abstract::One hundred and seventy six patients (81 controls, 95 receiving treatment) have entered a prospective randomized trial of long-term oral adjuvant razoxane (ICRF-159) following removal of a colorectal cancer. The median follow-up is 34 months. The treated patients in Dukes' groups B and C have a significantly longer di...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00254053
更新日期:1982-01-01 00:00:00
abstract:PURPOSE:The combination of docetaxel, cisplatin and 5-fluorouracil (DCF) is a newly developed chemotherapy regimen for esophageal cancer. Severe neutropenia is dose-limiting toxicity of docetaxel and it is well known to be frequently occurred during DCF chemotherapy. This study aimed to investigate the relationship bet...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04118-9
更新日期:2020-08-01 00:00:00
abstract:PURPOSE:The purpose of this study was to assess the therapeutic and toxicological effects of cesium chloride (CsCl) administration in mice bearing prostate cancer tumors. METHODS:Three CsCl dose titration studies were completed in tumor-bearing and non-tumor-bearing athymic nude mice. All mice were administered either...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0429-4
更新日期:2007-11-01 00:00:00
abstract:PURPOSE:Our study was designed to evaluate the efficacy and safety of everolimus in patients with pre-treated metastatic gastric and esophagus cancers in a US-based population focusing on biomarker correlation. METHODS:Patients with advanced upper GI adenocarcinomas who progressed after 1-2 prior regimens received eve...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-015-2744-5
更新日期:2015-07-01 00:00:00
abstract:PURPOSE:Fludarabine is a renally excreted agent that is an effective treatment for chronic lymphocytic leukemia (CLL), a disease predominantly of the elderly. We sought to determine whether age, renal function or pretreatment hematologic status predicted toxicity of fludarabine treatment for CLL. METHODS:We evaluated ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00280-002-0443-5
更新日期:2002-07-01 00:00:00
abstract::Elevations of serum lipid peroxide levels were demonstrated in mice after an equitoxic dose of doxorubicin. When BDF1 mice were injected with doxorubicin (20 mg/kg body weight, IP), lipid peroxide levels in sera were elevated 1 day after the injection and the levels declined on subsequent days. 5-Fluorouracil (400 mg/...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254735
更新日期:1979-01-01 00:00:00
abstract:PURPOSE:To confirm the efficacy and toxicity of gemcitabine and S-1 combination chemotherapy when used as a first-line therapy in patients with unresectable pancreatic cancer. METHODS:Patients with locally advanced or metastatic or recurrent pancreatic adenocarcinoma, which was histologically or cytologically proven, ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-009-1059-9
更新日期:2010-02-01 00:00:00
abstract:PURPOSE:The sequence bendamustine (B) + Irinotecan (I) followed by etoposide (E) + carboplatin (C) was hypothesized to increase progression-free survival (PFS) and overall survival (OS) in untreated extensive-disease small cell lung cancer (EDSCLC) patients compared to historical controls by exploiting mitotic catastro...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2869-6
更新日期:2015-11-01 00:00:00
abstract::In January 1983, the German Society of Pediatric Oncology started a cooperative trial (MAKEI 83) for non-testicular germ-cell tumors. The pilot phase closed in December 1985. The treatment regimen was stratified according to histology, tumor site and tumor stage. In malignant non-seminomatous germ-cell tumors (mNSGCTs...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00253238
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:The aim of this study is to examine the factors affecting sensitivity to cisplatin, carboplatin, and oxaliplatin in human colorectal tumor cell lines. METHODS:Caco-2, DLD-1, HCT-15, HCT116, LS180, SW620, and WiDr cells were used. Their growth inhibition by platinum derivatives was evaluated with a WST-1 assay ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0640-3
更新日期:2008-09-01 00:00:00