Abstract:
PURPOSE:The sequence bendamustine (B) + Irinotecan (I) followed by etoposide (E) + carboplatin (C) was hypothesized to increase progression-free survival (PFS) and overall survival (OS) in untreated extensive-disease small cell lung cancer (EDSCLC) patients compared to historical controls by exploiting mitotic catastrophe. Absent expression of ERCC-1 and expression of topoisomerases were hypothesized to be predictive for PFS and OS. METHODS:This was a phase I/IIa trial in 30 patients to determine the maximum tolerated dose (MTD) of B + I and the PFS of B + I E + C with secondary end points including overall response rate (ORR) and OS. Biomarkers measured by immunohistochemistry (IHC) obtained from diagnostic specimens were correlated with outcome. RESULTS:The MTD of B + I was not reached. During treatment with B + I, there were two grade 5 toxicities from neutropenic sepsis and metabolic encephalopathy. Other toxicities included fatigue, nausea/vomiting, diarrhea, and weight loss. For the sequence, the PFS and OS were 6.0 months and 10 months, respectively. The ORR for B + I and the sequence were 82% and 83%, respectively. Topoisomerase-2 expression was predictive for TTP and OS, but absent ERCC-1 expression was not, contrary to our hypothesis. CONCLUSIONS:B + I is an active regimen in EDSCLC. Toxicities included two grade 5 events but were otherwise manageable. The novel sequence B + I E + C increased PFS and OS compared to historical controls. Correlative studies are conflicting regarding the mechanism of action of this novel sequence.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Allendorf DJ,Bordoni RE,Grant SC,Saleh MN,Reddy VB,Jerome ML,Dixon PM,Miley DK,Singh KP,Robert Fdoi
10.1007/s00280-015-2869-6subject
Has Abstractpub_date
2015-11-01 00:00:00pages
949-55issue
5eissn
0344-5704issn
1432-0843pii
10.1007/s00280-015-2869-6journal_volume
76pub_type
杂志文章abstract:PURPOSE:This phase I first-in-human trial evaluated salirasib, an S-prenyl derivative of thiosalicylic acid that competitively blocks RAS signaling. METHODS:Patients with advanced cancers received salirasib twice daily for 21 days every 4 weeks. Doses were escalated from 100 to 200, 400, 600, and 800 mg. RESULTS:The ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1027-4
更新日期:2010-01-01 00:00:00
abstract:PURPOSE:To investigate any effect of a CYP3A4 inhibitor (ketoconazole) or inducer (rifampicin) on cediranib steady-state pharmacokinetics in patients with advanced solid tumours. METHODS:In two Phase I, open-label trials, patients received once-daily oral doses of cediranib alone [20 mg (ketoconazole study); 45 mg (ri...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-012-2038-0
更新日期:2013-02-01 00:00:00
abstract:PURPOSE:Troxacitabine (BCH-4556, l-(-)-OddC, Troxatyl) is a novel beta- l-nucleoside analogue with potent antineoplastic activity both in vitro and in several tumor models in vivo, and is presently in phase II clinical trials. The combination of the cytosine analogues troxacitabine and araC (1-beta- d-arabinofuranosylc...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0699-4
更新日期:2003-12-01 00:00:00
abstract:PURPOSE:Although anthracycline is a key agent in breast cancer treatment, its use is associated with the risk of cardiotoxicity. Recently, the value of combination therapy with docetaxel and cyclophosphamide was reported. Because the characteristics of paclitaxel differ on weekly versus tri-weekly administration, such ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-009-1137-z
更新日期:2010-05-01 00:00:00
abstract::Etoposide has been used in the treatment of a wide variety of neoplasms, including small-cell lung cancer, Kaposi's sarcoma, testicular cancer, acute leukemia, and lymphoma. Its current therapeutic use is limited by myelosuppression, particularly neutropenia. Pharmacodynamic studies of etoposide show that this toxicit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF00684866
更新日期:1994-01-01 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:PURPOSE:This study was performed to determine whether or not in cervical, ovarian and lung cancer cell lines, free radicals (ROS) play a role in cisplatin cytotoxicity and activation of the mitochondrial and JNK/p38 pathways. The role of the enzyme, dihydrodiol dehydrogenase (DDH1), in the activation/deactivation of th...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2739-2
更新日期:2015-06-01 00:00:00
abstract::Chronic myeloid leukaemia (CML) is an unusual malignancy in which myeloid progenitor cells are transformed by a single chromosomal translocation where the Bcr domain of chromosome 22 is placed adjacent to the proto-oncogene c-Abl of chromosome 9, resulting in constitutive Abl tyrosine kinase activity. This has a twofo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2556-z
更新日期:2014-10-01 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:While the target of many anticancer agents has been identified, the processes leading to killing of the cancer cells and the molecular basis of resistance to the drugs are not well understood. We used human gastrointestinal cancer cell lines and examined how anticancer agents induced cell killing and how the ch...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050861
更新日期:1999-01-01 00:00:00
abstract:PURPOSE:Our previous studies have reported the antitumor effect of oleandrin on osteosarcoma; however, its chemosensitizing effect in osteosarcoma treatment is still unknown. Therefore, we explored the sensitizing effects of oleandrin to cisplatin in osteosarcoma and investigated the potential mechanisms. METHODS:Afte...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3692-7
更新日期:2018-12-01 00:00:00
abstract::The study under discussion was a drug-drug interaction study in which the effect of ketoconazole, a potent CYP450 3A4 inhibitor, on the pharmacokinetics of Glivec (imatinib) was investigated. A total of 14 healthy subjects (13 male, 1 female) were enrolled in this study. Each subject received a single oral dose of ima...
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/s00280-004-0832-z
更新日期:2004-10-01 00:00:00
abstract:PURPOSE:ASNA1 is homologous to E. coli ArsA, a well characterized ATPase involved in efflux of arsenite and antimonite. Cells resistant to arsenite and antimonite are cross-resistant to the chemotherapeutic drug cisplatin. ASNA1 is also an essential ATPase for the insertion of tail-anchored proteins into ER membranes a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0762-2
更新日期:2009-02-01 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:PURPOSE:This dedicated QTc study was designed to evaluate the effect of the mammalian target of rapamycin inhibitor, ridaforolimus, on the QTc interval in patients with advanced malignancies. METHODS:We conducted a fixed-sequence, single-blind, placebo-controlled study. Patients (n = 23) received placebo on day 1 and ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1942-7
更新日期:2012-10-01 00:00:00
abstract:PURPOSE:Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3 testing for refractory/relapsed AML, is a non-genotoxic oral p53 activator. To optimize its dosing conditions, a number of clinical pharmacology characteristics were examined in this multi-center trial in patients with advanced solid tumors. ME...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3521-z
更新日期:2018-03-01 00:00:00
abstract:PURPOSE:Everolimus is a standard treatment option for advanced pancreatic neuroendocrine tumors (pNETs). This multicenter study evaluated the efficacy and safety of everolimus in low and intermediate grade advanced pNETs. METHODS:Tumors were graded according to the World Health Organization 2010 classification system....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-017-3421-7
更新日期:2017-10-01 00:00:00
abstract:PURPOSE:Differences in efficacy and toxicity between UDP-glucuronosyltransferase (UGT) 1A1*1/*1 and *1/*6 or *1/*28 genotypes remain unclear in Japanese patients. METHODS:Patients with advanced colorectal cancer who received irinotecan combined with 5-fluorouracil plus l-leucovorin (FOLFIRI) as first-line therapy were...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1485-8
更新日期:2011-08-01 00:00:00
abstract:PURPOSE:Transcatheter arterial chemoembolization (TACE) causes damage to liver function and decreases the activity of cytochrome P450 in patients with hepatocellular carcinoma (HCC). But there was no report on whether the activity of Phase II conjugating enzymes was affected in HCC patients after TACE treatment. The pu...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-009-1040-7
更新日期:2010-01-01 00:00:00
abstract::Treosulfan (L-threitol 1,4-bismethanesulfonate, Ovastat) is an alkylating agent and a structural analogue of busulfan. It has been established in the clinical chemotherapy of human ovarian carcinomas for several years and has additionally been shown to be effective against xenografted human breast carcinomas. No other...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00688319
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:To compare the response rates, toxicities and survival durations of elderly patients (70 years of age or more) with those of younger patients (less than 70 years of age) with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. PATIENTS AND METHODS:We analyzed retrospectively the data ...
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/s002800050689
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:Cyclosporine A (CyA) is able to inhibit P-glycoprotein (P-gp) and to increase cytotoxicity of some anticancer drugs, including etoposide. However, the effect of CyA on the distribution of etoposide in normal tissues, which could affect their toxicity, has not been studied extensively. The purpose of this study ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0784-3
更新日期:2004-08-01 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: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:To investigate the efficacy and safety of combination chemotherapy with biweekly paclitaxel plus infusional 5-fluorouracil and leucovorin in the treatment of patients with advanced or metastatic gastric cancer. PATIENTS AND METHODS:Chemonaive patients with histologically confirmed advanced or recurrent inopera...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0752-4
更新日期:2009-02-01 00:00:00
abstract:PURPOSE:The interindividual variability of vincristine pharmacokinetics is quite large, but the origins of this variability are not properly understood. The aim of this study was to develop a population pharmacokinetic model of vincristine in a paediatric population treated for solid tumour disease and evaluate the imp...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1541-4
更新日期:2011-11-01 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::Imidazoacridinones are a new class of highly potent antineoplastic agents synthesised at the Technical University of Gdansk. The pharmacophoric alkyldiamine group, which is also present in anthracenediones (e.g. ametantrone, mitoxantrone), has been shown to be responsible for their antineoplastic activity. In view of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050445
更新日期:1996-01-01 00:00:00
abstract::Unidirectional blood-brain barrier transfer of the lipophilic anticancer agents vincristine and vinblastine was studied in anesthetized rats, using an isolated, in situ brain perfusion technique. Drug binding to plasma constituents was also measured. Despite the high lipophilicity of these agents (the log octanol/phys...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02897227
更新日期:1990-01-01 00:00:00
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 o...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2095-z
更新日期:2013-04-01 00:00:00