Abstract:
PURPOSE:Erlotinib (Tarceva®), a potent small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase, has been evaluated to treat infants and children with primary brain tumors. The pharmacokinetics of erlotinib and its primary metabolite OSI-420 were characterized and exposure-safety associations were investigated. METHODS:This analysis involved patients enrolled in two clinical studies and receiving oral erlotinib once daily as part of treatment. Single-dose and steady-state erlotinib and OSI-420 plasma concentrations were assayed using HPLC-MS/MS methods. Population pharmacokinetic modeling and univariate covariate analysis evaluating demographic, clinical and selected CYP3A5, CYP3A4, ABCB1, and ABCG2 genotypes were performed. Associations between erlotinib and OSI-420 pharmacokinetics, and with toxicities (diarrhea and skin rash) occurring post-dose were explored. RESULTS:Data from 47 patients (0.7-19 years old) were collected and best fitted by one-compartment linear models. Erlotinib and OSI-420 apparent clearances (CL/F and CLm/Fm) were higher in patients < 5 years compared to older patients (mean CL/F: 6.8 vs 3.6 L/h/m2, and mean CLm/Fm: 79 vs 38 L/h/m2, p < 0.001), and were 1.62-fold and 1.73-fold higher in males compared to females (p < 0.01). Moreover, CL/F was 1.53-fold higher in wild-type patients than in patients heterozygous or homozygous mutant for ABCG2 rs55930652 (p < 0.05). Most of the toxicities reported were grade 1. No associations were found between drug pharmacokinetics and drug-induced toxicities. CONCLUSIONS:Erlotinib therapy was well tolerated by pediatric patients with primary brain tumors. No dosing adjustments based on age or patient characteristics are recommended for this patient population.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Reddick SJ,Campagne O,Huang J,Onar-Thomas A,Broniscer A,Gajjar A,Stewart CFdoi
10.1007/s00280-019-03921-3subject
Has Abstractpub_date
2019-10-01 00:00:00pages
829-838issue
4eissn
0344-5704issn
1432-0843pii
10.1007/s00280-019-03921-3journal_volume
84pub_type
临床试验,杂志文章,多中心研究abstract:PURPOSE:A metronomic schedule of chemotherapy (resulting in a greater frequency of drug delivery) has shown efficacy in head and neck cancer. Our aim was to investigate the overall survival in tongue cancer patients with metronomic neoadjuvant chemotherapy with bleomycin compared to those with surgery alone. METHODS:I...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3141-4
更新日期:2016-10-01 00:00:00
abstract:PURPOSE:Thyroid cancers with unsatisfactory curative effect nowadays are the most common malignant tumors of the endocrine system. Apoptosis evasion, a hallmark of cancer, has driven the search of stimulating novel cell death way in cancer therapy. This review aims to explore the relationship between autophagy and thyr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-013-2363-y
更新日期:2014-03-01 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:BACKGROUND:Inhibitors of heat shock protein (Hsp) 90 induce apoptosis in multiple myeloma (MM) cells, but the molecular mechanisms underlying this cytotoxic outcome are not clear. Here, we investigate the effect of IPI-504, a novel and highly soluble inhibitor of the Hsp90 ATPase activity, on the unfolded protein respo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0546-0
更新日期:2008-05-01 00:00:00
abstract:PURPOSE:HER2-targeted therapy with trastuzumab and (CF/X) prolonged overall survival (OS) in metastatic HER2neu+ gastric carcinoma (GC). Lapatinib inhibits both EGFR and HER2neu. We investigated the efficacy and safety of lapatinib with epirubicin (E) + CF/X in GC according to HER2neu and EGFR status. METHODS:Tumors f...
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/s00280-018-3667-8
更新日期:2018-10-01 00:00:00
abstract::A 62-year-old patient on long-term haemodialysis who developed an inoperable T2N3Mo squamous-cell carcinoma of the larynx was treated with weekly low-dose methotrexate (MTX) after failing to respond to radiotherapy. The patient was initially given one dose of 10 mg MTX (6 mg/m2) as a 1-h infusion, then he received thr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050528
更新日期:1996-01-01 00:00:00
abstract::The radiosensitizing activity, acute toxicity, and pharmacokinetics of a new hypoxic cell radiosensitizer, potassium 2-nitroimidazole-1-acetohydroxamate (KIH-802), were compared with those of misonidazole (MISO) and etanidazole (SR-2508). The radiosensitizing activity of KIH-802 was slightly higher than that of MISO a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02897255
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Following a previously published pre-clinical validation, this phase I study evaluated the safety, maximum tolerated dose, anti-tumour activity and immune status of a gemcitabine-chloroquine combination as a first- or late-line treatment in patients with metastatic or unresectable pancreatic cancer. METHODS:In...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3446-y
更新日期:2017-11-01 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:PURPOSE:Ifosfamide is a cornerstone of chemotherapy in bone and soft-tissue sarcoma. Results of pharmacokinetic studies indicate that the optimal schedule of ifosfamide should be repeated doses over several days. With the development of 5-day infusion devices, we developed and evaluated a 5-day infusion regimen of ifos...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-009-1054-1
更新日期:2010-02-01 00:00:00
abstract:PURPOSE:Sarcomas are a rare and heterogeneous variant of cancer. The standard of care treatment involves surgical resection with radiation in high-risk patients. Despite appropriate treatment approximately 50 % of patients will suffer and die from recurrent disease. The purpose of this article is to review the current ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00280-016-3055-1
更新日期:2016-11-01 00:00:00
abstract:PURPOSE:Interferon-alpha (IFN-alpha) has been shown to control symptoms, reduce platelet counts, and reduce the bone marrow megakaryocyte mass in patients with essential thrombocythemia (ET). A semisynthetic protein-polymer conjugate of IFN-alpha 2b (PEG-IFN2b) increases the serum half-life of IFN-alpha 2b. We conducte...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-002-0533-4
更新日期:2003-01-01 00:00:00
abstract::Forty-one previously treated patients with advanced Hodgkin's disease were treated with a combination chemotherapy regimen -- ABVD (adriamycin, bleomycin, velbe/vincristine, imidazole carboxamide). Complete remission was achieved in three patients (7%), partial remission in 23 (56%), and no response in 15 patients (37...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00258297
更新日期:1979-01-01 00:00:00
abstract:PURPOSE:We have developed and evaluated a CNS-targeted chemotherapy regimen based on the pharmacokinetic properties of the individual drugs in the combination. PATIENTS AND METHODS:In a twin-track study, 16 patients with secondary CNS lymphoma (SCNSL) and 8 with primary CNS lymphoma (PCNSL) were treated with IDARAM wh...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s00280-003-0737-2
更新日期:2004-04-01 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:PURPOSE:Several studies have identified amino acid residues located on the hydrophobic side of the helix that forms transmembrane domain 6 (TM6) of the ABC transporter P-glycoprotein (Pgp) as being important for function. The purpose of this study was to determine if alterations to residues on the hydrophilic side coul...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800100354
更新日期:2001-11-01 00:00:00
abstract:PURPOSE:Because of the recurrence of hepatocellular carcinoma (HCC) at the graft after liver transplantation, circulating HCC cells may be present during the anhepatic period. Intravenous doxorubicin (DOX) is used during the anhepatic period to combat these cells; however, pharmacokinetics data have been poorly analyze...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2311-x
更新日期:2013-12-01 00:00:00
abstract:PURPOSE:The objective of this study was to compare the pharmacokinetics and safety of two tablet formulations containing 500 mg of capecitabine (CAS number 154361-50-9) in patients with colon, colorectal or breast cancer. METHODS:The study was a multicentric, open label, randomized, two-treatment, two-period, two-sequ...
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/s00280-012-2007-7
更新日期:2013-02-01 00:00:00
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 musta...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00256165
更新日期:1986-01-01 00:00:00
abstract::The present paper reviews several studies performed between 1977 and 1986 in Singapore on the 10-year survival outcome of treatment for stage I and II hepatocellular carcinoma (HCC). Of 801 HCC patients evaluated, only 2 survivors (0.3%) remained in complete remission for 13 and 14 years, respectively. One had receive...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00687123
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:Nasopharyngeal carcinoma (NPC) is one of the most commonly diagnosed cancers worldwide with significantly high prevalence in Southern China. Chemoprevention of cancer with alkylating agent compounds could potentially reverse, suppress, or prevent cancer progression. Cisplatin (CIS) is an antineoplastic or cytot...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3536-5
更新日期:2018-05-01 00:00:00
abstract::P388 murine leukemic cells lines which were resistant (P388R) or sensitive (P388S) to adriamycin (adr) were used to evaluate the potential utility of in vitro clonogenic assays for detecting and quantitating the number of adr-resistant cells present in a cell mixture. The progeny of P388S cells that had been exposed f...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00269030
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:To evaluate the outcomes of intraperitoneal chemotherapy (IP) compared with those of intravenous chemotherapy (IV) in patients with advanced ovarian cancer after neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) or primary debulking surgery (PDS). METHODS:Patients with advanced epithelial ov...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3591-y
更新日期:2018-07-01 00:00:00
abstract:PURPOSE:One of the major problems of cancer chemotherapy is the development of multidrug resistance (MDR) phenotype. Among the numerous mechanisms of MDR, a prominent one is the increased expression of membrane transporter proteins, the action of which leads to decreased intracellular drug concentration and cytotoxicit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1385-y
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:An intact and fully functional multiprotein DNA replication complex (DNA synthesome) from human as well as from murine mammary carcinoma cells was first isolated and characterized in our laboratory. The human cell synthesome supports the in vitro origin-specific simian virus 40 (SV40) DNA replication reaction i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050046
更新日期:2000-01-01 00:00:00
abstract::Resistance to the clinically used platinum-based drugs cisplatin and carboplatin represents a major limitation to their clinical effectiveness. Using cisplatin-sensitive and -resistant human ovarian carcinoma cell lines previously characterized in terms of their major underlying mechanisms of resistance, we attempted ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686636
更新日期:1994-01-01 00:00:00
abstract::Breast cancer is presently the most predominant tumor type and the second leading cause of tumor-related deaths among women. Although advancements in diagnosis and therapeutics have momentously improved, chemoresistance remains an important challenge. Tumors oppose chemotherapeutic agents through a variety of mechanis...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-020-04222-w
更新日期:2021-01-09 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
abstract:PURPOSE:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent due to its selective cytotoxicity to transformed cells. However, most human hepatocellular carcinomas (HCC) develop resistance to TRAIL. Thus, there is an urgent need to investigate the molecular targets and the unde...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1763-0
更新日期:2012-03-01 00:00:00
abstract:PURPOSE:Paclitaxel and docetaxel are two taxanes approved for the treatment of non-small-cell lung cancer (NSCLC). However, there is limited evidence regarding the efficacy of docetaxel in NSCLC previously treated with a paclitaxel-platinum doublet (PP). The aim of our study was to evaluate the response to docetaxel in...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2522-9
更新日期:2014-10-01 00:00:00