Abstract:
OBJECTIVE:SDX-101 is the non-cyclooxygenase 2-inhibiting R-enantiomer of the non-steroid anti-inflammatory drug etodolac, and has anti-tumour activity in chronic lymphocytic leukaemia (CLL). SDX-308 and SDX-309 are more potent, structurally related indole-pyran analogues of SDX-101. The current study was performed to investigate and quantify the cytotoxic potentiating effects resulting from a combination of either SDX-101, SDX-308 or SDX-309 with standard cytotoxic agents used in the CLL treatment today. METHODS:The lymphoma cell line U937-gtb was used, together with primary tumour cells isolated from seven CLL patients. Combinations between chlorambucil and each one of the agents etodolac, SDX-101, SDX-308 and SDX-309 were studied. In addition, SDX-309 was combined with fludarabine, doxorubicin or vincristine. Both simultaneous and sequential exposures were explored using the median-effect method. RESULTS:Most combinations were additive, which could be of clinical benefit since SDX-101 has been shown to be well tolerated. At the 70% effect level, synergy was observed between SDX-308 and chlorambucil in U937-gtb cells and in two-third of the CLL samples. Since chlorambucil is the most important drug in CLL therapy today and SDX-308 is presently targeted as the lead clinical candidate, this combination would be interesting for further studies. Vincristine and SDX-309 were synergistic in two-fourth of CLL samples. CONCLUSIONS:To conclude, the non-COX-inhibiting etodolac-derivatives SDX-101, SDX-308 and SDX-309 are potential candidates for combination treatment of CLL. Especially, SDX-308 in combination with chlorambucil warrants further evaluation.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Lindhagen E,Nissle S,Leoni L,Elliott G,Chao Q,Larsson R,Aleskog Adoi
10.1007/s00280-006-0400-9subject
Has Abstractpub_date
2007-09-01 00:00:00pages
545-53issue
4eissn
0344-5704issn
1432-0843journal_volume
60pub_type
杂志文章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::Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0148-7
更新日期:2006-08-01 00:00:00
abstract:PURPOSE:The purpose of these extensive non-clinical studies was to assess pharmacokinetics and dispositional properties of sunitinib and its primary active metabolite (SU12662). METHODS:Sunitinib was administered in single and repeat oral doses in mice, rats, and monkeys. Assessments were made using liquid-chromatogra...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0917-1
更新日期:2009-09-01 00:00:00
abstract::MKT-077 (1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4- oxothiazolidin-2-ylidenemethyl] pyridinium chloride), a novel rhodacyanine dye in phase I/II clinical trials, may provide a new approach to cancer therapy based on the accumulation in the mitochondria of the cells of certain carcinomas, for example, ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050898
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND:Adjuvant chemotherapy is gaining an increasing role in resectable gastric cancer. Customizing chemotherapy on the basis of chemosensitivity may improve outcome, and putative predictive molecular markers have been mostly evaluated in Asian patients. We profiled key DNA and damage signaling factors and correla...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2181-2
更新日期:2013-07-01 00:00:00
abstract:PURPOSE:ABT-888 inhibits poly(ADP-ribose) polymerase (PARP) and may enhance the efficacy of chemotherapy and radiation in CNS tumors. We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics (PK) of ABT-888 in a non-human primate (NHP) model that is highly predictive of human CSF penetration. METHODS:ABT-8...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1044-3
更新日期:2010-02-01 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:Based on the preclinical evidence of topoisomerase I (Topo-1) upregulation by mitomycin C(MMC) and decreased NF-kappaB activation by celecoxib, we evaluated combinations of irinotecan/MMC and irinotecan/MMC/celecoxib in patients with advanced solid malignancies. PATIENTS-METHODS:Initially, patients received MM...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0826-3
更新日期:2009-05-01 00:00:00
abstract::In the original article, corresponding author's given name and family name are flipped. It should be "Siqing Fu" rather than "Fu Siqing". ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 已发布勘误
doi:10.1007/s00280-016-3002-1
更新日期:2016-04-01 00:00:00
abstract:PURPOSE:Ibrutinib is an orally administered, irreversible Bruton's tyrosine kinase inhibitor for treatment of B-cell malignancy. This study evaluated the effects of single-dose ibrutinib at therapeutic and supratherapeutic exposures on cardiac repolarization in healthy subjects. METHODS:Part 1 used an open-label, two-...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3471-x
更新日期:2017-12-01 00:00:00
abstract:PURPOSE:Valproic acid (VPA), a widely used antiepileptic, also inhibits histone deacetylase (HDAC), and is undergoing evaluation as an anti-cancer agent. We studied the pharmacokinetics of VPA in the plasma and cerebrospinal fluid (CSF) in a non-human primate model that is highly predictive of human CSF penetration to ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0519-3
更新日期:2008-04-01 00:00:00
abstract::The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 29 patients aged a median of 70 years between January of 1991 and May of 1993. The patients received intravesical instillation of...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00686923
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:The platinum agent oxaliplatin could be useful in treatment of cancer in pregnant women, but it is fetotoxic in rats and its effect on the human fetus is unknown. METHODS:Oxaliplatin was administered to a 25-year-old pregnant woman with metastatic rectal cancer from 20 to 30 weeks gestational age as part of th...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0731-9
更新日期:2009-01-01 00:00:00
abstract:PURPOSE:6-Gingerol, a major biochemical and pharmacological active ingredient of ginger, has shown anti-inflammatory and antitumor activities against various cancers. Searching for natural products with fewer side effects for developing adjunctive therapeutic options is necessary. METHODS:The effects of 6-gingerol on ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03999-9
更新日期:2020-02-01 00:00:00
abstract:PURPOSE:Capecitabine is an oral chemotherapeutic agent, already used in breast and colon cancer. Previous data showed encouraging results in the treatment of recurrent ovarian cancer. The aim of this study was to describe activity and toxicity of capecitabine in patients with platinum resistant or refractory ovarian ca...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-009-0958-0
更新日期:2009-10-01 00:00:00
abstract:PURPOSE:Since the hypothesis that solid tumors cause angiogenesis by secreting pro-angiogenic factors was introduced, research on angiogenesis has proceeded continuously. Development of inhibitors targeting the angiogenic tyrosine kinases, to block downstream signal transduction pathways, has become an important approa...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-016-2961-6
更新日期:2016-05-01 00:00:00
abstract:PURPOSE:Epigenetic agents are among the newly targeted therapeutic strategies being studied with intense interest for patients with multiple myeloma. Here, we demonstrate the antitumor activity of a phenylbutyrate-based histone deacetylase (HDAC) inhibitor, (S)-HDAC42, and identify its possible targets in myeloma cells...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1501-z
更新日期:2011-08-01 00:00:00
abstract:UNLABELLED:A hemopoietin with the ability to accelerate both platelet and granulocyte recovery after intensive chemotherapy would have great clinical utility. The recombinant fusion protein composed of human granulocyte-macrophage colony-stimulating factor and interleukin-3 (PIXY321), showed some promise in early adult...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050733
更新日期:1998-01-01 00:00:00
abstract:PURPOSE:We reported the first case of phenytoin intoxication due to the concomitant use of phenytoin and TS-1, together with a review of the literature regarding the occurrence of phenytoin intoxication due to the concomitant use of phenytoin and fluoropyrimidine antitumor drugs such as fluorouracil (5-FU) and tegafur ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0621-6
更新日期:2008-08-01 00:00:00
abstract:PURPOSE:Artemisinins are now established drugs for treatment of malaria. These agents have been shown to possess impressive anti-cancer properties. We have investigated the role of artemisone (ATM), a novel derivative of artemisinin (ART) in a cancer setting both alone and in combination with established chemotherapeut...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1355-4
更新日期:2011-03-01 00:00:00
abstract::We treated 101 patients with advanced (stage III and IV) lymphosarcoma and reticulosarcoma at first presentation of the disease or in relapse according to a protocol combining initial chemotherapy, complementary radiotherapy on icebergs, supplementary chemotherapy, and, finally, active immunotherapy. The overall compl...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00257149
更新日期:1978-01-01 00:00:00
abstract::2'-deoxycoformycin (2'-dCF; Pentostatin), a stoichiometric inhibitor of mammalian adenosine deaminase (ado deaminase), exhibits immunosuppressive and antilymphocytic activity in animal test systems. A clinical pharmacology/phase I study of 2'-dCF administered as a single agent has been completed (18 patients). Dose le...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00435411
更新日期:1980-01-01 00:00:00
abstract:PURPOSE:P-glycoprotein (P-gp), encoded by MDR1 (or ABCB1), is important in anticancer drug delivery and resistance. We evaluated alterations in P-gp-mediated transport of anticancer agents due to the MDR1 G1199A polymorphism. METHODS:Using stable recombinant epithelial cells expressing wild-type (MDR1 (wt)) or G1199A ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0906-4
更新日期:2009-06-01 00:00:00
abstract::The effect of acetazolamide (A.A.) on the antineoplastic activity of 1-phthalidyl 5-fluorouracil (PH-FU) against rat and mouse solid tumors was examined. A.A., an inhibitor of liver PH-FU hydrolase, had no antitumor activity but greatly enhanced the activity of PH-FU when coadministered. The potentiation was evaluated...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00255286
更新日期:1986-01-01 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:PURPOSE:This phase II study was performed to evaluate the efficacy and safety of cisplatin/pemetrexed combined with 15 mg/kg of bevacizumab followed by pemetrexed/bevacizumab maintenance therapy as first-line chemotherapy in advanced non-squamous non-small cell lung cancer (NSCLC) limited to epidermal growth factor rec...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3573-0
更新日期:2018-06-01 00:00:00
abstract:PURPOSE:To assess the activity and safety of combined folinic acid (FA), 5-fluorouracil (5-FU) and mitomycin C (MMC) in metastatic breast cancer patients previously treated with at least two chemotherapy regimens. PATIENTS AND METHODS:A total of 104 consecutive patients were enrolled for treatment with FA 100 mg/m(2) ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-002-0495-6
更新日期:2002-10-01 00:00:00
abstract::The value of estrogen receptor (ER) status in the prediction of tumor response to combination chemotherapy was retrospectively analyzed in breast cancer patients selected for prospective controlled trials of chemotherapy (85 with advanced disease and 256 with operable tumors). All patients were previously untreated wi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00255456
更新日期:1980-01-01 00:00:00
abstract:BACKGROUND:Cediranib (RECENTIN™) is an oral, highly potent VEGF inhibitor. This study evaluated the effect of food on the pharmacokinetics of cediranib and compared the administration of continual cediranib via two dosing strategies using this as a platform to investigate pharmacodynamic imaging biomarkers. METHODS:Si...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s00280-010-1534-3
更新日期:2011-09-01 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