Abstract:
:Bcl-2 family proteins are the key regulators of the intrinsic apoptotic pathway, controlling the point-of no-return and setting the threshold to engage the death machinery in response to chemical damage. Bcl-2 proteins have emerged as attractive targets for anti-cancer drug development. Navitoclax is a selective, potent, orally bioavailable, small molecule Bcl-2 inhibitor. Primary endpoints assessed the safety and pharmacokinetic (PK) interactions between navitoclax in combination with carboplatin/paclitaxel or paclitaxel alone in patients with solid tumors The study comprised two arms, one a combination of navitoclax with paclitaxel and carboplatin, the second with navitoclax and paclitaxel alone. Nineteen patients were enrolled in this study. The most frequently reported treatment-emergent AEs were alopecia (57.9 %), anemia (52.6 %), nausea (52.6 %), constipation (42.1 %), diarrhea (42.1 %), fatigue (42.1 %), neutropenia (36.8 %), thrombocytopenia (36.8 %), vomiting (31.6 %), decreased appetite (31.6 %), dehydration (26.3 %), and hypomagnesaemia (26.3 %). In the light of significant hematological and non-hematological toxicity the study was ended before de-escalation of navitoclax. Only one partial response was obtained at any dose tested, thus lowering doses could not have increased efficacy. It is the combination of toxicity with modest efficacy that led to discontinuation. No apparent PK interaction was observed between navitoclax and carboplatin or paclitaxel and the combination of navitoclax and paclitaxel had modest anti-tumor activity.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Vlahovic G,Karantza V,Wang D,Cosgrove D,Rudersdorf N,Yang J,Xiong H,Busman T,Mabry Mdoi
10.1007/s10637-014-0116-3subject
Has Abstractpub_date
2014-10-01 00:00:00pages
976-84issue
5eissn
0167-6997issn
1573-0646journal_volume
32pub_type
杂志文章abstract::An in vitro assay, which evaluates drug effect on 3H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activiti...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175294
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:To summarize the safety experience obtained from phase II clinical trials conducted with trabectedin as single-agent therapy in patients with advanced solid tumors. METHODS:This retrospective analysis includes 1,132 patients exposed to trabectedin in 19 phase II trials carried out between February 1999 and Apr...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9662-0
更新日期:2012-06-01 00:00:00
abstract::Interleukin-4 is a highly pleiotropic T-cell derived lymphokine that has been reported to stimulate a host cell-mediated antitumor response. Recombinant human interleukin-4 (rhuIL-4) is currently undergoing clinical phase I trials. We have studied the growth modulating effects of rhuIL-4 on a variety of freshly explan...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00944180
更新日期:1992-11-01 00:00:00
abstract:BACKGROUND:Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00874443
更新日期:1994-01-01 00:00:00
abstract:BACKGROUND:BTH1677 is a beta glucan pathogen associated molecular pattern (PAMP) currently being investigated as a novel cancer therapy. Here, the initial safety and pharmacokinetic (PK) results of BTH1677 in healthy subjects are reported. SUBJECTS AND METHODS:In the Phase 1a single-dosing study, subjects were randomi...
journal_title:Investigational new drugs
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10637-016-0325-z
更新日期:2016-04-01 00:00:00
abstract::Background Metformin use is associated with reduced cancer risk in epidemiological studies and has preclinical anti-cancer activity in ovarian cancer models. The primary objective of this phase I study was to determine the recommended phase II dose (RP2D) of metformin in combination with carboplatin/paclitaxel in pati...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-00920-7
更新日期:2020-10-01 00:00:00
abstract::Background C-Met, which is frequently activated in multiple cancers, has been implicated in tumor formation, progression, metastasis, angiogenesis, and resistance to multiple therapies. MK-8033 is a small-molecule inhibitor of c-Met that binds preferentially to the activated conformation, and has demonstrated anti-tum...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-018-0567-z
更新日期:2018-10-01 00:00:00
abstract:PURPOSE:To assess the maximum well-tolerated dose (MWTD), dose limiting toxicity (DLT), pharmacokinetics (PK) and pharmacodynamics of zibotentan, a novel specific endothelin-A receptor antagonist, in patients with metastatic prostate cancer. METHODS:Patients with metastatic, castrate-resistant prostate cancer (CRPC) w...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-009-9318-5
更新日期:2011-02-01 00:00:00
abstract::The novel compound N-benzoxazol-2-yl-N'-1-(isoquinolin-3-yl-ethylidene)-hydrazine (EPH136) has been shown to exhibit antitumor activity in vitro and in vivo. A COMPARE analysis showed that the patterns of cellular effects of EPH136 are not related to any of 175 standard antitumor agents with a known mechanism of actio...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9156-x
更新日期:2009-06-01 00:00:00
abstract::Fourteen patients with acute leukemia in relapse were treated with difluoromethylornithine (DFMO) alone or in combination with methylglyoxal-bis(guanylhydrazone) (MGBG) as part of Phase I studies. Five patients included in the trial exhibited morphologic evidence of cellular differentiation during the course of treatm...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00170848
更新日期:1989-07-01 00:00:00
abstract::Coptis chinensis Franch. has been extensively used in traditional Chinese medicine. The chemical structure of oxyepiberberine, as an alkaloid isolated from Coptis chinensis Franch., has been previously studied. However, anti-cancer effects and underlying mechanisms of oxyepiberberine need to be explored. This study ai...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-01006-0
更新日期:2020-09-30 00:00:00
abstract::LY2457546 is a potent and orally bioavailable inhibitor of multiple receptor tyrosine kinases involved in angiogenic and tumorigenic signalling. In biochemical and cellular assays, LY2457546 demonstrates potent activity against targets that include VEGFR2 (KDR), PDGFRβ, FLT-3, Tie-2 and members of the Eph family of re...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9640-6
更新日期:2012-06-01 00:00:00
abstract::Background PF-06650808 is a novel anti-Notch3 antibody-drug conjugate (ADC) able to deliver an auristatin-based cytotoxic payload to target cells. In this first-in-human, dose-finding, phase I study (NCT02129205), we investigated safety, pharmacokinetics, immunogenicity, and preliminary antitumor activity of single-ag...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10637-019-00754-y
更新日期:2020-02-01 00:00:00
abstract::Background To determine the feasibility and efficacy of olanzapine, which is approved by the Pharmaceuticals and Medical Devices Agency as multi acting receptor targeted antipsychotic agent of the thienobenzodiazepine class, for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients undergoing conti...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/s10637-017-0487-3
更新日期:2018-02-01 00:00:00
abstract::Twenty-four patients with a variety of solid tumors entered a Phase I trial with 4-demethoxydaunorubicin, a new analogue of daunorubicin. The drug was given as a single oral dose of 10-60 mg/m2 repeated every 3-4 weeks. Leukopenia was the dose-limiting toxicity. Other toxic effects included mild to moderate nausea and...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175378
更新日期:1984-01-01 00:00:00
abstract::Osimertinib is a molecularly targeted agent used to treat non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) T790M mutation. However, its efficacy and safety profile when patients have poor performance status (PS) is unknown. Therefore, we conducted an open-label, multi-center,...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-00943-0
更新日期:2020-12-01 00:00:00
abstract::This report shows that N-acylation of the protein kinase C (PKC) substrate Arg-Lys-Arg-Thr-Leu-Arg-Arg-Leu (RKRTLRRL) provides it with a potent inhibitory activity against PKC. N-myristoyl-RKRTLRRL inhibited Ca2(+)- and phosphatidylserine (PS)-dependent histone phosphorylation catalyzed by PKC with a 50% inhibitory co...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175084
更新日期:1991-05-01 00:00:00
abstract::Drug lag, which delays patients' access to medicinal products, is typically associated with pharmaceutical regulations. To shorten drug lag, health authorities may establish new policies to liberalize the regulations, a step that is important in countries, such as Taiwan, with consumer demand for imported novel therap...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-018-00715-x
更新日期:2019-10-01 00:00:00
abstract::Purpose Anticancer agents are known to increase cancer-associated thrombosis (CAT) onset. CAT onset rate is reported to be 1.92% in cisplatin-based therapy, 6.1% in paclitaxel plus ramucirumab combination therapy, and 11.9% in bevacizumab monotherapy. Because immune checkpoint inhibitors (ICIs) cause a sudden increase...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-019-00881-6
更新日期:2020-08-01 00:00:00
abstract::Taxol was administered as a 24-hour continuous infusion at 250 mg/m2 in this Phase II trial in patients with adenocarcinomas of the upper gastrointestinal tract (UGIT). Twenty-five patients were entered between July 1991 and June 1992, twenty-three were eligible and were evaluated for toxicity and twenty-two were asse...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00873804
更新日期:1995-01-01 00:00:00
abstract::Colon cancer is the third most malignant neoplasm in the world and it remains today an important cause of death, especially in western countries. In this study, we have evaluated the chemopreventive efficacy of morin on tissue lipid peroxidation and antioxidant status, which are used as biomarkers in 1,2-dimethylhydra...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9136-1
更新日期:2009-02-01 00:00:00
abstract::Although immune checkpoint inhibitors have improved the survival of small cell lung cancer (SCLC) patients, their efficacy in SCLC patients who relapsed after systemic chemotherapy is unclear. This retrospective study aimed to investigate the utility of treatment with atezolizumab plus carboplatin and etoposide in SCL...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-00983-6
更新日期:2020-08-11 00:00:00
abstract::Recent clinical trials carried out in patients with advanced cancer have shown that recombinant TRAIL administration is usually safe and well tolerated when used either alone or in association with chemotherapeutic drugs. Notably, anticancer chemotherapy can be associated to cardiomiopathy. We have here demonstrated t...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9627-8
更新日期:2012-06-01 00:00:00
abstract::Lactoferrin has gained extensive attention due to its ample biological properties. In this study, recombinant human lactoferrin carrying humanized glycosylation (rhLf-h-glycan) expressed in the yeast Pichia pastoris SuperMan5, which is genetically glycoengineered to efficiently produce functional humanized glycoprotei...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-01020-2
更新日期:2020-10-16 00:00:00
abstract:BACKGROUND:The primary objective of this Phase I study was to determine the maximum tolerated dose (MTD) and recommended phase II dose for Tomudex and Doxorubicin when given in combination to patients with advanced metastatic cancer. The secondary objective was to assess the toxicity profile. PATIENTS AND METHODS:Star...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/B:DRUG.0000047105.38511.2a
更新日期:2005-01-01 00:00:00
abstract::We have recently developed a liposomal nanoparticle (LNP) formulation of irinotecan based on loading method that involves formation of a complex between copper and the water soluble camptothecin. The loading methodology developed for irinotecan was evaluated to develop a LNP topotecan formulation (referred to herein a...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9832-8
更新日期:2013-02-01 00:00:00
abstract::This study was conducted to assess the efficacy and toxicity of suramin administered using a fixed dose schedule in patients with advanced renal cell carcinoma. Fourteen eligible patients with advanced renal cell carcinoma were enrolled and treated on a fixed dose schedule of suramin administered over 12 weeks. Surami...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/a:1006331518952
更新日期:1999-01-01 00:00:00
abstract::Ergot alkaloids are psychoactive and vasoconstricting agents of the fungus Claviceps purpurea causing poisoning such as ergotism in medieval times (St. Anthony's Fire). This class of substances also inhibits tumor growth in vitro and in vivo, though the underlying mechanisms are unclear as yet. We investigated six erg...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-014-0168-4
更新日期:2015-02-01 00:00:00
abstract::A retrospective analysis was performed on the medical charts of 160 cancer patients who received esorubicin (ESO or 4'deoxydoxorubicin) in a Phase I clinical trial. The purpose of the review was to characterize the incidence of local venous reactions to this investigational doxorubicin (DOX) analog. The impact of prop...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00217666
更新日期:1987-01-01 00:00:00
abstract::Acquired resistance to tamoxifen (Tam) is a critical problem in breast cancer therapy. Therefore, new potential strategies for Tam-resistant breast cancer are needed recently. In this study, we synthesized a novel histone deacetylase (HDAC) inhibitor, MHY218, for the development of potent inhibitors of HDAC and evalua...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9752-z
更新日期:2012-10-01 00:00:00