Abstract:
:We propose a mathematical model that takes into account a classical maximum tolerated dose (MTD) chemotherapy regimen (whose primary targets are the tumor cells) as well as a metronomic chemotherapy regimen (whose primary targets are the tumor endothelial cells) for the administration of temozolomide (Temodal(®)) in order to compare the effectiveness of these two types of protocols. The model is built from 4 natural hypotheses: (H1) without treatment the tumor growth follows a Gompertz model, (H2) endothelial cells are more sensitive to temozolomide than cancer cells, (H3) the anti-angiogenic effect blocks tumor growth, and (H4) endothelial cells are more genetically stable than cancer cells and thus less likely to develop resistance to temozolomide. Then, we compared a conventional MTD regimen of 200 mg/m(2) temozolomide J1-J5 every 28 days with a daily metronomic regimen of 85 mg/m(2)/day for cycles of 42 days. Our mathematical model shows that the metronomic regimen induces tumor regression through anti-angiogenic effects while the MTD regimen fails to do so, due to the emergence of temozolomide resistance in cancer cells. Overall, our model is consistent with clinical observations and provides an interesting tool toward the personalization of anticancer treatments, through optimization of dose and schedule of chemotherapy based on individual patient characteristics.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Faivre C,Barbolosi D,Pasquier E,André Ndoi
10.1007/s00280-013-2095-zsubject
Has Abstractpub_date
2013-04-01 00:00:00pages
1013-9issue
4eissn
0344-5704issn
1432-0843journal_volume
71pub_type
杂志文章abstract::The chemotherapeutic effects of all-trans-retinoic acid (atRA) are mediated by the retinoic acid receptor beta (RARbeta), but RARbeta expression is reduced in a number of head and neck carcinoma (HNSCC) cells which causes resistance to RA treatment in half the patients with HNSCC. The possible mechanism for the reduce...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0970-3
更新日期:2005-11-01 00:00:00
abstract:PURPOSE:Cancer, a major public health problem, exhibits significant redox alteration. Thioredoxin (Trx) system, including Trx and Trx reductase (TrxR), as well as Trx-interacting protein (TXNIP) play important roles in controlling the cellular redox balance in cancer cells. In most cancers, Trx and TrxR are usually ove...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-019-03869-4
更新日期:2019-09-01 00:00:00
abstract:BACKGROUND:The docetaxel/cisplatin (DC) combination is an active regimen against advanced/metastatic non-small-cell lung cancer (NSCLC), and bevacizumab (B) improves the efficacy of frontline chemotherapy. This phase II study was designed in order to explore the efficacy and safety of DCB regiment in this setting. MET...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-012-2037-1
更新日期:2013-03-01 00:00:00
abstract:PURPOSE:Decitabine is a nucleoside analog used in the treatment for myelodysplastic syndrome. The compound requires intracellular conversion to its triphosphate to become active. Decitabine triphosphate has, however, never been quantified in peripheral blood mononuclear cells (PBMCs) from patients. METHOD:This article...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1850-x
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Docetaxel has marked inter-patient PK variability, and metabolic phenotypic probes may enable individualised dosing. This is the first report directly comparing the erythromycin breath test (EBT) (a CYP3A4 probe) with the antipyrine clearance test (ACT), (a general CYP-P450/predominant CYP3A4 probe) for the ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1676-y
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:The purpose of this investigation was to synthesize a series of carbonate and carbamate derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma non-toxic metabolite of penclomedine (PEN) seen in patients. DM-PEN has been observed to be an active antitumor agent in mouse human xenograft tumor models and...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-0933-9
更新日期:2009-09-01 00:00:00
abstract:PURPOSE:Neoadjuvant CT-P6, a trastuzumab biosimilar, demonstrated equivalent efficacy to reference trastuzumab in a phase 3 trial of HER2-positive early-stage breast cancer (EBC) (NCT02162667). We report post hoc analyses evaluating pathological complete response (pCR) and breast pCR alongside additional efficacy and s...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00280-019-03920-4
更新日期:2019-10-01 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:BACKGROUND:Veliparib (ABT-888) is an oral PARP inhibitor expected to increase gemcitabine activity. This phase I determined the maximal tolerable dose (MTD), dose-limiting toxicities (DLT), antitumor activity, pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib combined with gemcitabine. METHODS:Patients wit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-017-3409-3
更新日期:2017-09-01 00:00:00
abstract:PURPOSE:In this exploratory study, the effect of postprocedural flushing with crystalloids after oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) on platinum concentrations in peritoneal tissue, blood, and drain fluid was studied. Interpatient variability in oxaliplatin pharmacokinetics and the relat...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04107-y
更新日期:2020-07-01 00:00:00
abstract::We have developed and validated a selective analytical procedure, based on ion-exchange normal-phase liquid chromatography with fluorescence detection and liquid-liquid extraction, for the analysis of vinblastine (VBL) in biological matrices. The assay is suitable for the determination of the parent compound and its m...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686174
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate safety and toxicity of chronomodulated capecitabine administered in the morning and at noon according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of first-line XELOX chemotherapy in patients with metastatic colorectal cancer. METHODS:A total...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3067-x
更新日期:2016-07-01 00:00:00
abstract:PURPOSE:Oxaliplatin (OHP) in combination with 5-fluorouracil/leucovorin (FOLFOX) is clinically used as frontline therapy in patients with advanced colorectal carcinoma (CRC), with response rates ranging from 46 to 71%. This combination is now considered a standard treatment for metastatic CRC and also in the post-opera...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1476-9
更新日期:2011-04-01 00:00:00
abstract::Lanreotide (BIM 32014), a somatulin analogue, was found to be as effective as castration in a rat prostate tumor model. Therapeutic benefit was also demonstrated in the hormone-resistant phase of this tumor model. The activity of lanreotide may be due to a reduction in the levels of growth factors such as insulin grow...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00685857
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:This study aimed at evaluating if pharmacokinetic and pharmacodynamic data from the first few patients treated with an investigational monoclonal antibody in a dose-escalation study can be used to guide the early initiation of potentially more efficacious combination regimens. METHODS:Emerging pharmacokinetic ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-017-3328-3
更新日期:2017-06-01 00:00:00
abstract::Dexniguldipine-HCl (DNIG)--a prospective clinical modulator of p170-glycoprotein (pgp170)-mediated multidrug resistance (MDR)--was evaluated in a drug-accumulation assay in MDR murine leukemia cell strain F4-6RADR expressing pgp170. The compound elevated low accumulation of either doxorubicin (DOX), daunorubicin (DNR)...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685872
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:The purpose of this study was to evaluate the expression of ser-miRNAs at different periods during treatment and analyze their relationship with therapeutic response and prognosis in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy combined with trastuzumab (NCCT). METHODS:Venous blood w...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03937-9
更新日期:2019-11-01 00:00:00
abstract:PURPOSE:High-dose methotrexate (HD-MTX) is widely used in the treatment of non-Hodgkin lymphoma (NHL), but the pharmacokinetic properties of HD-MTX in Chinese adult patients with NHL have not yet been established through an approach that integrates genetic covariates. The purposes of this study were to identify both ph...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04058-4
更新日期:2020-05-01 00:00:00
abstract:PURPOSE:Aldehyde dehydrogenases class-1A1 (ALDH1A1) and class-3A1 (ALDH3A1) have been associated with resistance to cyclophosphamide (CP) and its derivatives. We have previously reported the downregulation of these enzymes by all-trans retinoic acid (ATRA). METHODS:In this study, we used siRNA duplexes as well as retr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0233-6
更新日期:2007-01-01 00:00:00
abstract:PURPOSE:To investigate the effect of granulocyte colony-stimulating factor (G-CSF) on the pharmacokinetics and pharmacodynamics of the new morpholino anthracycline drug MX2. METHODS:A total of 25 patients with advanced malignant disease participated in a dose-escalation study in the first cycle of treatment given i.v....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050761
更新日期:1998-01-01 00:00:00
abstract:PURPOSE:This study evaluated the tolerability, pharmacokinetics, and preliminary antitumor activity of EZN-2208, a water-soluble poly(ethylene) glycol conjugate of SN38. METHODS:Patients with advanced malignancies were enrolled in dose-escalating cohorts (3 + 3 design). EZN-2208 was administered as a 1-h intravenous i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-013-2149-2
更新日期:2013-06-01 00:00:00
abstract::The toxic effect of 3'-deoxyadenosine N1-oxide (3'-dANO) on mice, on their different organs, and on Ehrlich ascites tumor cells was studied. In both healthy and tumour-bearing animals, the lethal dose for 10% of the mice receiving i.p. injections (LD10) of 3'-dANO was estimated to be about 300 mg/kg x 4 days in one mo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686398
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:Chinese patients have been enrolled in multiple Phase III trials of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza); however, the pharmacokinetic (PK) profile of olaparib has not been investigated in this population. This two-part, open-label Phase I study was, therefore, carried out to det...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03799-1
更新日期:2019-05-01 00:00:00
abstract::A patient with acute nonlymphoblastic leukemia in relapse and anthracycline cardiomyopathy was treated with AMSA in combination with cytosine arabinoside and thioguanine (AAT). Induction of remission was accomplished after one course of therapy without development of congestive heart failure. Radionuclide studies done...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257232
更新日期:1982-12-01 00:00:00
abstract::Methylene blue (MB) is a phenothiazine with radio and photosensitizing properties and anti-tumoral activity. Our group has shown that MB was capable of inhibiting the in vitro growth of erythroleukemic cells with multidrug resistance (MDR). However, there are no studies comparing the cytotoxicity of this molecule for ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-1014-3
更新日期:2005-12-01 00:00:00
abstract::The effects of BCNU, CCNU, methyl-CCNU, streptozotocin, and chlorozotocin on calmodulin activity were studied in vitro and in vivo. Preincubation of BCNU, CCNU, and methyl-CCNU with calmodulin produced a concentration-dependent inhibition of in vitro calmodulin activity expressed as stimulation of cyclic nucleotide ph...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00434354
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:The study investigated the effects of pemetrexed, gefitinib, and their combination on human colorectal cancer cells. METHODS:Six human colorectal cancer cells were exposed to pemetrexed, gefitinib, and their combination. Antitumor effects were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium br...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2251-5
更新日期:2013-10-01 00:00:00
abstract:PURPOSE:5-Fluorouracil is the most commonly used drug for the treatment of colon cancer, yet clinical resistance to this drug is frequently observed in patients making this drug ineffective. Thus, identification of gene responsible for 5-FU resistance is of utmost importance. METHODS:Cellular cytotoxicity and expressi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2794-8
更新日期:2015-09-01 00:00:00
abstract:PURPOSE:Radiotherapy (RTx) has been considered as the treatment for locally advanced squamous cell carcinoma of the head and neck (SCCHN). However, with only conventional fractionation (Cfx), response rates are relatively low. In this study, we report the results of hyperfractionation (Hfx) RTx with concurrent docetaxe...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0370-y
更新日期:2007-08-01 00:00:00
abstract::Tumor angiogenesis is essential for tumor growth and metastasis formation. Luminex methodology was used to measure the levels of four angiogenic cytokines in cell culture medium and in the plasma of mice bearing human tumors. We obtained plasma and conditioned culture medium from 12 different human tumor cell lines. T...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0572-5
更新日期:2003-04-01 00:00:00