Abstract:
:6-[Bis-(2-chloroethyl)-amino]-6-deoxy-D-glucose (C-6) is a new glucose-containing nitrogen mustard that has significant activity for murine P388 leukemia with relative sparing of bone marrow in mice. The in vitro myelotoxicity of C-6 compared with that of melphalan, a clinically active, myelosuppressive nitrogen mustard, was determined in the CFU-C assay in human bone marrow samples obtained from normal volunteers. There was no significant difference between the myelosuppressive actions of C-6 and melphalan at any of the concentrations used except for 4.0 microM, at which C-6 was significantly (P less than 0.05) more toxic than melphalan. Both agents decreased the number of bone marrow cell colonies to approximately 12% of control at 6.6 microM (1 h incubation), which is a good approximation of melphalan's CxT (concentration by time) in man. We used the human tumor stem cell assay (HTSCA) to investigate in vitro antitumor activity. We obtained two specimens of malignant melanoma and two of malignant ovarian carcinoma from patients not previously treated with chemotherapy. The antitumor activity of melphalan was either similar to or greater than that of C-6 at all concentrations utilized against any of the four tumor specimens, except at 1.3 microM for tumor I. In particular, there was no significant difference in the antitumor activities of the two agents at 6.6 microM. These results suggest that C-6 will not be less myelosuppressive than melphalan at doses that produce equivalent antitumor activity in man. In addition, C-6 did not demonstrate increased myelotoxicity for normal human bone marrow cells incubated in glucose-deficient medium as against medium containing 300 mg% glucose at any of the concentrations used. This suggests that C-6 is not transported into normal human bone marrow cells via the glucose transport system, despite the presence of a glucose moiety within the molecule.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Lazarus P,Dufour M,Isabel G,Panasci LCdoi
10.1007/BF00256165subject
Has Abstractpub_date
1986-01-01 00:00:00pages
148-52issue
2eissn
0344-5704issn
1432-0843journal_volume
16pub_type
杂志文章abstract:PURPOSE:S-1 has systemic activity for locally advanced pancreatic cancer (LAPC). Here, the efficacy and safety of induction gemcitabine (GEM) and S-1 (GS) followed by chemoradiotherapy (CRT) and systemic chemotherapy using S-1 for LAPC were assessed. METHODS:The treatment consisted of four cycles of induction GS (S-1 ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3350-5
更新日期:2017-07-01 00:00:00
abstract::Nine children with soft tissue sarcomas, five of them rhabdomyosarcomas with initial metastatic disease, (one patient, partial response, one patient), refractory primary, (two patients, relapse, five patients) were treated with a combination of high-dose VP16 (100 mg/m2 daily for 5 days) and cisplatin (40 mg/m2 daily ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685912
更新日期:1994-01-01 00:00:00
abstract::Dihydroartemisinin (DHA), a more water-soluble active metabolite of artemisinin derivatives, is safe and the most effective antimalarial analog of artemisinin. In the present investigation, we assessed the effect of DHA on vascular endothelial growth factor (VEGF) expression and apoptosis in chronic myeloid leukemia (...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0002-y
更新日期:2006-01-01 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:Although chemotherapeutic protocols that include chloroethylnitrosoureas (CENUs), such as 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), have been a mainstay of treatment for glioblastomas, the clinical outcomes ha...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050023
更新日期:2000-01-01 00:00:00
abstract::Any approach applied to drug discovery and development by the medical community and pharmaceutical industry has a direct impact on the future availability of improved, novel, and curative therapies for patients with cancer. By definition, drug discovery is a complex learning process whereby research efforts are direct...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-003-0653-5
更新日期:2003-07-01 00:00:00
abstract::Anticipating the renewed clinical trial of the antitumor agent 2-amino-1,3,4-thiadiazole (AT, NSC-4728), we have studied the pharmacologic fate of AT-5-14C in beagle dogs. The drug was only minimally metabolized in 5 h; the radioactivities in the urine, and particularly in the plasma, resided almost entirely in unchan...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00255274
更新日期:1980-01-01 00:00:00
abstract:PURPOSE:To explore the safety and tolerability of combining two epigenetic drugs: decitabine (a DNA methyltransferase inhibitor) and panobinostat (a histone deacetylase inhibitor), with chemotherapy with temozolomide (an alkylating agent). The purpose of such combination is to evaluate the use of epigenetic priming to ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2501-1
更新日期:2014-10-01 00:00:00
abstract::This phase I study was carried out to determine the maximal tolerated dose of carboplatin (Car) together with a fixed dose of etoposide (E) and to recommend the optimal dose for a phase II study. The dose of E was 100 mg/m2 given i.v. on days 1-3, and the starting dose of Car was 200 mg/m2 given i.v. on day 1. The dos...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00685718
更新日期:1990-01-01 00:00:00
abstract::Saturable elimination of 5-FU is exhibited in rats during constant infusions. Over the range of 3-480 mg/m2/h, total-body clearance of 5-FU decreases from 600 ml/min/m2 to less than 90 ml/min/m2. Previously published values for catabolism of 5-FU by rat hepatocytes can be used to simulate the plasma concentrations of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00434346
更新日期:1985-01-01 00:00:00
abstract::We conducted a double-blind, randomized crossover study to compare the toxicity and antiemetic efficacy of the 5-hydroxytryptamine3 receptor antagonist batanopride with that of metoclopramide in 21 chemotherapy-naive patients receiving at least 70 mg/m2 cisplatin. The study was terminated when hypotension was observed...
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/BF00685516
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:Acute kidney injury (AKI) is a common and serious adverse effect of cisplatin-based chemotherapy. However, traditional markers of kidney function, such as serum creatinine, are suboptimal, because they are not sensitive measures of proximal tubular injury. We aimed to determine whether the new urinary biomarker...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-015-2880-y
更新日期:2015-11-01 00:00:00
abstract::In a pilot study of cyclical chemotherapy in patients with poor-prognosis non-Hodgkin's lymphoma (NHL), high-dose methotrexate (MTX) 1 g/m2 with folinic acid rescue was given as initial treatment and then between cycles of a single-arm CHOP combination administered every 4 weeks. Of 21 patients with previously untreat...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254195
更新日期:1983-01-01 00:00:00
abstract::The clinical formulation of leucovorin (5-CHO-FH4) is a mixture of diastereoisomers with markedly different pharmacologic properties. Comparatively little information is available concerning the cellular pharmacology of reduced folate stereoisomers, due largely to the difficulty in preparing sufficient quantities of t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02897229
更新日期:1990-01-01 00:00:00
abstract::This report describes the physicochemical and pharmacokinetic parameters of seven chlorambucil esters, which were compared with those of chlorambucil. These esters were designed as chlorambucil prodrugs to increase the brain penetration and concentration vs time profile of chlorambucil within the CNS for potential tre...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686229
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Polyamines are biologic cations necessary for normal cell growth. Polyamine analogues have been shown to be effective inhibitors of tumor growth. We tested the effect of the polyamine analogues 1,1 9-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4), N1,N11-bis(ethyl)norspermine (BE-3-3-3) and 1,15-bis(ethy...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050643
更新日期:1997-01-01 00:00:00
abstract::Pegylated liposomes have been studied for nearly two decades. However, fewer pharmacological studies about its application in daunorubicin (DNR) than those in doxorubicin have been reported. In order to conduct a complete pharmacokinetic study, radiolabeled DNR was encapsulated in pegylated liposomes. Its in vitro dru...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0076-6
更新日期:2006-05-01 00:00:00
abstract:PURPOSE:The aim was to investigate in patients receiving doxorubicin whether any alteration in myocardial oxidative metabolism or blood flow as assessed by positron emission tomography (PET) could be observed either after the first dose of the drug, or during its chronic administration. METHODS:Six female non-heart-fa...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800051005
更新日期:2000-01-01 00:00:00
abstract:PURPOSE:The objectives of these analyses were to (1) develop a semimechanistic-physiologic population pharmacokinetic/pharmacodynamic (PK/PD) model to describe neutropenic response to pemetrexed and to (2) identify influential covariates with respect to pharmacodynamic response. PATIENTS AND METHODS:Data from 279 pati...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0077-5
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:The role of adjuvant therapy in pancreatic cancer remains controversial. Gemcitabine given systemically seems to be effective; intra-arterial chemotherapy (IAC) has a deep rationale. PATIENTS AND METHODS:The goal was to evaluate the impact of postoperative IAC followed or not by systemic gemcitabine in pati...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s00280-006-0200-2
更新日期:2006-10-01 00:00:00
abstract:BACKGROUND:The cyclin-dependent kinase inhibitor flavopiridol increases irinotecan- and fluorouracil-induced apoptosis. We conducted a phase I trial of FOLFIRI + flavopiridol in patients with advanced solid tumors. DESIGN:FOLFIRI + flavopiridol were administered every 2 weeks. Based on sequence-dependent inhibition, f...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1269-1
更新日期:2010-11-01 00:00:00
abstract:PURPOSE:This study was performed to determine the maximum tolerated dose (MTD) and toxicity of vinorelbine when used in combination with doxorubicin and methotrexate with leucovorin rescue in women with metastatic breast cancer. METHODS:Enrolled in the study were 23 women with metastatic breast cancer who had not rece...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050929
更新日期:1999-01-01 00:00:00
abstract:PURPOSE:The artemisinin class of anti-malarial drugs has shown significant anti-cancer activity in pre-clinical models. Proposed anti-cancer mechanisms include DNA damage, inhibition of angiogenesis, TRAIL-mediated apoptosis, and inhibition of signaling pathways. We performed a phase I study to determine the maximum to...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3533-8
更新日期:2018-03-01 00:00:00
abstract:PURPOSE:To gain a better understanding of the impact of postprogression survival (PPS) and post-trial anticancer therapy on overall survival (OS) in first-line pancreatic cancer patients. METHODS:A literature search identified 54 randomized trials, focusing on gemcitabine monotherapy to eliminate effects of heterogene...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00280-017-3263-3
更新日期:2017-03-01 00:00:00
abstract::A total of 13 patients receiving bone marrow transplants (BMT) for treatment of different haematological diseases were investigated. Conditioning therapy preceding BMT consisted of fractionated total-body irradiation (12 Gy) and high-dose chemotherapy with cyclophosphamide (2 +/- 60 mg/kg). Patients stratified to be a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689585
更新日期:1989-01-01 00:00:00
abstract::Cisplatin-induced emesis is one of the most feared side effects in cancer treatment. High-dose metoclopramide may prevent only 30-40% of cases of acute emesis. Investigations to test the efficacy of new antiemetics are mandatory. We compared the efficacy, toxicity, and patients' preference for tropisetron, a new 5-hyd...
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/BF00688329
更新日期:1996-01-01 00:00:00
abstract::In early studies of the antitumor drug 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1nitrosourea (methyl-CCNU), animal models consistently predicted that the compound would be nephrotoxic in humans. Nephrotoxicity in cancer patients who had received methyl-CCNU was not confirmed until about 6 years after clinical trials b...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257241
更新日期:1982-12-01 00:00:00
abstract:PURPOSE:In clinical trials, the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) administered concomitantly with first-line cytotoxicity chemotherapy failed to confer a survival benefit to patients with non-small-cell lung cancer (NSCLC). The aim of this study was to test whether paclitaxel followe...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1347-4
更新日期:2011-03-01 00:00:00
abstract:PURPOSE:Inhibitors of DNA (cytosine-5)-methyltransferases (DNMT) are active antineoplastic agents. We conducted the first-in-human phase I trial of 5-fluoro-2'-deoxycytidine (FdCyd), a DNMT inhibitor stable in aqueous solution, in patients with advanced solid tumors. Objectives were to establish the safety, maximum tol...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-014-2674-7
更新日期:2015-03-01 00:00:00
abstract:PURPOSE:Gastric cancer is one of the leading cancerous diseases worldwide. It is diagnosed often at the advanced stage for which chemotherapy is the main treatment option. The prognosis remains poor for metastatic, especially the diffuse type, gastric cancers. We investigated the efficacy of intravenously administered ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1222-3
更新日期:2010-09-01 00:00:00