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 with advanced solid tumors received veliparib (10-40-mg PO BID) on chemotherapy weeks with gemcitabine 500-750-mg/m2 IV on days 1, 8, and 15 (28-day cycle), or on days 1 and 8 (21-day cycle). The MTD, DLT, adverse events, PK, and PD were evaluated. RESULTS:Eleven patients were enrolled on the 28-day schedule. The 28-day schedule was considered intolerable and amended to a 21-day schedule, with 20 patients enrolled. Grade ≥ 3 adverse events were myelosuppression-related. The MTD was determined to be 750-mg/m2 gemcitabine IV on days 1 and 8- and 20-mg PO veliparib BID days 1-14 on a 21-day schedule. Of 27 patients evaluable for response, 3 had PR and 15 had SD. There was no evidence of any major drug-drug interaction, and PK parameter values for veliparib, gemcitabine, and dFdU were as expected. Analysis of PBMCs showed evidence of PARP inhibition and DNA damage associated with therapy. CONCLUSIONS:Gemcitabine at 750-mg/m2 IV on days 1 and 8 combined with veliparib at a dose of 20-mg PO BID days 1-14 on a 21-day schedule is relatively well-tolerated, with manageable, expected toxicities. Clinical responses were observed in a pretreated population of patients, suggesting that this combination should be further evaluated in the phase II setting.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Stoller R,Schmitz JC,Ding F,Puhalla S,Belani CP,Appleman L,Lin Y,Jiang Y,Almokadem S,Petro D,Holleran J,Kiesel BF,Ken Czambel R,Carneiro BA,Kontopodis E,Hershberger PA,Rachid M,Chen A,Chu E,Beumer JHdoi
10.1007/s00280-017-3409-3subject
Has Abstractpub_date
2017-09-01 00:00:00pages
631-643issue
3eissn
0344-5704issn
1432-0843pii
10.1007/s00280-017-3409-3journal_volume
80pub_type
杂志文章,多中心研究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::Patients with carcinoid syndrome usually die from carcinomatosis, rather than the pharmacological effects of the tumour. Functioning carcinoid tumours are resistant to radiotherapy. Twenty-four different cytotoxic drugs or combinations have been used to treat the carcinoid syndrome, but only actinomycin D, cyclophosph...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00258469
更新日期:1981-01-01 00:00:00
abstract::A highly sensitive enzyme-linked immunosorbent assay (ELISA) for etoposide (EP) was developed, which is capable of accurately measuring as little as 40 pg EP/ml. Anti-EP sera were obtained by immunizing rabbits with EP conjugated with mercaptosuccinyl bovine serum albumin (MS.BSA) using N-[beta-(4-diazophenyl)ethyl]ma...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689094
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:The relationships between pharmacokinetic parameters of unchanged cisplatin (CDDP) and several markers for nephrotoxicity after CDDP infusion (80 mg/m2) over 2 and 4 h were quantitated in patients with various cancers (lung, stomach and colon cancers and mediastinal tumor). METHODS:Plasma and urinary levels of...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050548
更新日期:1996-01-01 00:00:00
abstract::The orally bioavailable matrix metalloproteinase inhibitor MMI270 reduces tumour growth metastasis in preclinical models. We assessed the feasibility and pharmacokinetic interactions of combining MMI270 with 5-fluorouracil (5-FU) and folinic acid (FA). Entered into the study were 33 patients with advanced colorectal c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-004-0856-4
更新日期:2005-01-01 00:00:00
abstract::Imatinib is the treatment of choice for FIP1L1-PDGFRalpha (F/P+) positive myeloproliferative neoplasms, but little is known about optimal dose and duration of treatment to maintain complete molecular remission once achieved. We describe a case of F/P+ patients who started imatinib and reached a molecular remission, bu...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0858-8
更新日期:2009-05-01 00:00:00
abstract:PURPOSE:As a follow-up to our previous findings that platinum drugs induce a key enzyme in polyamine catabolism, gene expression profiling and mathematical modeling were used to define the effects of cisplatin and oxaliplatin on the expression of polyamine metabolic pathway genes in A2780 human ovarian carcinoma cells....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0325-3
更新日期:2007-05-01 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:PURPOSE:Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma (ASTS) patients, and due to the limited efficacy of second or third line therapies in those patients, we designed a Phase II study to determine the activity of this new regimen....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0263-0
更新日期:2007-02-01 00:00:00
abstract::Thymidine (dThd) concentrations have been measured in the sera of normal subjects and solid tumor cancer patients by means of a sensitive high-pressure liquid chromatographic assay to determine whether natural and methotrexate (MTX)-induced fluctuations were large enough to alter the toxicity of MTX to marrow. The mea...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00434388
更新日期:1981-01-01 00:00:00
abstract:PURPOSE:Capecitabine is a prodrug that undergoes metabolism in three steps to form an active 5-fluorouracil (5-FU). The first step is primarily catalyzed by liver carboxylesterases (CES) 1. Here, we examined the effects of CES1 variants on pharmacokinetics and toxicity of capecitabine. METHODS:We enrolled postoperativ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04087-z
更新日期:2020-06-01 00:00:00
abstract:PURPOSE:To compare the response, survival, hematological and non-hematological toxicities of gemcitabine administrated at fixed-dose rate infusion (10 mg/m(2)/min, FDR) and standard 30 min infusion in patients with advanced non-small-cell lung cancer (NSCLC). METHODS:Electronic databases of MEDLINE, EMBASE and Cochran...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析
doi:10.1007/s00280-012-1974-z
更新日期:2012-12-01 00:00:00
abstract::Between December 1982 and November 1990, 31 patients with advanced urothelial carcinoma were treated with one of two combination chemotherapy regimens. A total of 20 patients were treated with 3 mg/m2 mitomycin C and 300 mg/m2 cyclophosphamide given intravenously every 10-14 days and with 180 mg/m2 5-fluorouracil (5-F...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00686944
更新日期:1992-01-01 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:The purpose of this study was to determine the potential utility of a novel algorithm to calculate individual GFR values in cancer patients. Based on carboplatin AUC measurements the algorithm-based values were compared with results related to other routinely used equations. METHODS:The association between mea...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1537-0
更新日期:2011-09-01 00:00:00
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 i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0400-9
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:In a phase I clinical trial of oxaliplatin (OPT) in combination with paclitaxel (PXL), a pharmacokinetic interaction was observed when OPT was given as a 2-h i.v. infusion followed by a 1-h i.v. infusion of PXL. The purpose of this study was to use a rat model to evaluate whether the pharmacokinetic interact...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-002-0531-6
更新日期:2002-12-01 00:00:00
abstract:PURPOSE:Doxorubicin-based chemotherapy is limited by the development of dose-dependent left ventricular dysfunction and congestive heart failure caused by reactive oxygen species (ROS). Uncoupling proteins (UCP) can inhibit mitochondrial ROS production as well as decrease myocyte damage from exogenous ROS. Prior studie...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1441-7
更新日期:2011-06-01 00:00:00
abstract::The toxicity of single doses of the anthracycline epirubicin was compared in the rat after either the intravenous (i.v.; 2-6 mg/kg) or intraperitoneal (i.p.; 4-8 mg/kg) administration of the drug. These doses produced comparable acute toxicity that was characterised by a dose-dependent, transient reduction in body wei...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257620
更新日期:1989-01-01 00:00:00
abstract::Characterization of the pharmacokinetics of 2-FLAA has been completed in seven patients receiving 18 or 25 mg/m2 daily X 5 of 2-FLAMP over 30 min. Assuming 2-FLAMP was instantaneously converted to 2-FLAA, the plasma levels of 2-FLAA declined in a biexponential fashion. Computer fitting of the plasma concentration-time...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00256699
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:Studies were conducted on oryzalin (3,5-dinitro-N,N-di(n-propyl)sulfanilamide), a widely used dinitroaniline sulfonamide herbicide, which was identified from plant extracts as an inhibitor of mitogen- and growth factor-mediated intracellular free Ca2+ ([Ca2+]i) signalling in mammalian cells. METHODS AND RESULT...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050703
更新日期:1997-01-01 00:00:00
abstract::The pharmacokinetics of soluble oral prednisolone were studied during induction therapy in six children with acute lymphoblastic leukaemia. There was a three- to four-fold variation in the pharmacokinetics of total and free prednisolone. For total prednisolone, the mean elimination half-life was relatively short (1.37...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00435843
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:The purpose of this article is to report the first case of markedly increased anticoagulant activity of warfarin when used in combination with doxifluridine, given as a replacement for capecitabine. METHODS:International normalized ratio (INR) of a 73-year-old female patient receiving warfarin was increased af...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1249-5
更新日期:2010-10-01 00:00:00
abstract:PURPOSE:Although intra-arterial chemotherapy (IAC) is commonly used for treating intraocular retinoblastoma, it is not a systemic therapy. We aimed to investigate whether the addition of intravenous chemotherapy (IVC) before IAC administration had any effects (whether beneficial or adverse) on patient outcomes. METHOD...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-020-04036-w
更新日期:2020-04-01 00:00:00
abstract:PURPOSE:This exploratory phase II clinical trial evaluated the antitumor activity, safety profile and pharmacokinetics of PM00104 (Zalypsis(®)) 3 mg/m(2) 1 h every 3-week intravenous infusion in patients with advanced and/or metastatic urothelial carcinoma progressing after first-line platinum-based chemotherapy. METH...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2419-7
更新日期:2014-04-01 00:00:00
abstract::Tumor-tissue and plasma concentrations of platinum were studied prospectively in two groups of eight patients who were suffering from advanced non-small-cell lung cancer. Treatments including two different schedules of cisplatin administration (25 vs 100 mg/m2 on day 1) were compared. At 30 min after the beginning of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689280
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:To determine the maximum tolerated dose (MTD) of perifosine (NSC 639966), an alkylphospholipid modulator of signal transduction, using different oral loading and maintenance regimens in an effort to avoid gastrointestinal toxicity while seeking maximal sustained plasma concentrations. METHODS:Thirty-one patien...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2569-7
更新日期:2014-11-01 00:00:00
abstract:PURPOSE:This phase I trial evaluated the maximum tolerated dose, safety and preliminary efficacy of lapatinib, a HER1, HER2 dual kinase inhibitor plus bortezomib, a proteasome inhibitor, in adult patients with advanced malignancies. METHODS:Patients were enrolled in a standard 3 + 3 design with lapatinib (L) 750, 1000...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03947-7
更新日期:2019-11-01 00:00:00
abstract:OBJECTIVE:Docetaxel given orally as monotherapy results in low bioavailability of <10%. Previous studies have indicated that the intestinal efflux pump P-glycoprotein (P-gp) prevents uptake from the gut resulting in low systemic exposure to docetaxel. The purpose of this study was to determine the degree of enhancement...
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/s00280-004-0864-4
更新日期:2005-01-01 00:00:00
abstract::PANC02 is a unique experimental animal tumor that fails to respond significantly to any known clinically active antitumor agent. In this regard, the murine ductal adenocarcinoma resembles its human counterpart. To study the mechanism for its intrinsic resistance to 6-thioguanine (TG), we compared the metabolism of the...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00684850
更新日期:1992-01-01 00:00:00