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 vomiting. Sixty mg/m2 was found to be the maximum tolerated dose in patients with fair tolerance to chemotherapy and normal liver function. Similar hematologic toxicity was reported in patients with very extensive prior chemotherapy or diffuse bone and/or liver metastases receiving 50 mg/m2. However, the wide range of the WBC nadirs reported with the same dose in 'good risk' cases, suggest that 40 mg/m2, increased up to 50 mg/m2 in the absence of significant myelotoxicity, could be more safely proposed as starting dose for Phase II trials. Pharmacokinetic studies were performed in five patients given a single dose of 40-60 mg/m2. IMI-30 (NSC 256439) appears to be rapidly absorbed and rapidly eliminated from plasma by means of a rapid and extensive biotransformation to 13-OH-idarubicin. The 13-dihydroderivative was present at higher and more prolonged levels than the parent compound, with an elimination half-life of about 40 hours.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Kaplan S,Sessa C,Willems Y,Pacciarini MA,Tamassia V,Cavalli Fdoi
10.1007/BF00175378subject
Has Abstractpub_date
1984-01-01 00:00:00pages
281-6issue
3eissn
0167-6997issn
1573-0646journal_volume
2pub_type
杂志文章abstract:BACKGROUND:Dacomitinib (PF-00299804) is an oral, irreversible, small molecule inhibitor of human epidermal growth factor receptor-1, -2, and -4 tyrosine kinases. METHODS:This phase I, open-label, dose-escalation study (clinicaltrials.gov: NCT00783328) primarily evaluated the safety and tolerability of dacomitinib by d...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9789-z
更新日期:2012-12-01 00:00:00
abstract::Transcription factor Specificity protein 1 (Sp1) and its downstream target survivin (inhibitor of apoptosis protein), play major roles in the pathogenesis of various cancers. Ewing Sarcoma (ES) is a common soft tissue/bone tumor in adolescent and young adults. Overexpression of survivin is also linked to the aggressiv...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-016-0417-9
更新日期:2017-04-01 00:00:00
abstract::Purpose Among alkaloids, abundant secondary metabolites in plants, aporphines constitute a class of compounds with interesting biological activities, including anticancer effects. The present study evaluated the anticancer activities of 14 substances, including four aporphine derivatives acquired through the biomonito...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-019-00784-6
更新日期:2020-02-01 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::Purpose Hepatic arterial infusion chemotherapy (HAIC) is one of the options to treat unresectable hepatocellular carcinoma (HCC). The majority of HCC patients suffer great pain in the course of HAIC treatment. To improve the quality of life and the efficacy of HAIC treatment, the causes of pain, the choice of an analg...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-01009-x
更新日期:2020-10-01 00:00:00
abstract::We explored whether barasertib (AZD1152), a selective Aurora B kinase inhibitor, is a substrate for P-glycoprotein (Pgp, MDR1), breast cancer resistance protein (BCRP), and multidrug resistance protein 2 (MRP2) in vitro. Cell survival, drug transport, and competition experiments with barasertib pro-drug and the more a...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-013-9923-1
更新日期:2013-10-01 00:00:00
abstract::Castrate-Resistant Prostate-Cancer (CRPC) is one of the most common malignancies occurring in men. Unfortunately, even if several recently approved agents clinically improved the outcome of CRPC patients, none of these is curative especially for a splice version of the Androgen Receptor (AR) AR-V7, which is a variant ...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/s10637-018-0653-2
更新日期:2018-12-01 00:00:00
abstract:OBJECTIVE:To determine the recommended dose for phase II trials of elisidepsin (PM02734, Irvalec®) in combination with erlotinib in patients with advanced malignant solid tumors. METHODS:Open-label, dose-escalating, phase I study of intravenous elisidepsin administered weekly (days 1, 8 and 15) over 3 h as a flat dose...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-015-0305-8
更新日期:2016-02-01 00:00:00
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, pote...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-014-0116-3
更新日期:2014-10-01 00:00:00
abstract::Over forty papers describing correlations between in vitro human tumor sensitivity to a variety of chemotherapeutic agents and the in vivo response of patients to those agents have been published since the publication in 1978 by Salmon and Hamburger of their results of a human tumor colony-forming chemosensitivity ass...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/BF00173788
更新日期:1984-01-01 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::Gemcitabine (GEM) is a novel nucleoside analogue with a unique mechanism of action. Preliminary studies have shown a mild, schedule-dependent toxic profile with a broad range of MTDs and promising antitumor activity in various solid tumors. This phase I study describes the infusion length-effect relationships of low- ...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/a:1005817024382
更新日期:1997-01-01 00:00:00
abstract::Fifty-four evaluable patients with SCLC previously treated with chemotherapy received either N-methylformamide or spirogermanium. There was one partial response to N-methylformamide. The median survival times for patients treated with N-MF and spirogermanium were 11.7 and 12.6 weeks respectively. Five patients treated...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00177255
更新日期:1990-05-01 00:00:00
abstract:OBJECTIVE:Axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, is metabolized primarily by cytochrome P450 (CYP) 3A with minor contributions from CYP1A2, CYP2C19, and glucuronidation. Co-administration with CYP inhibitors may increase systemic expos...
journal_title:Investigational new drugs
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10637-010-9511-6
更新日期:2012-02-01 00:00:00
abstract::B cell prolymphocytic leukemia (B-PLL) is a rare and aggressive disease that is associated with poor survival. Although initially asymptomatic patients do not require therapy, most patients will progress and inevitably require treatment. More than 50% of patients with B-PLL carry abnormalities in the TP53 tumor suppre...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-00902-9
更新日期:2020-10-01 00:00:00
abstract:PURPOSE:Cytotoxic and anti-angiogenic drugs are efficacious in malignancies. This trial was undertaken to evaluate the toxicity of a novel regimen combining docetaxel and lenalidomide. PATIENTS AND METHODS:Patients with advanced solid tumors were eligible. Docetaxel was administered on day 1, and lenalidomide was give...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9200-x
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND:Therapeutic approaches to marginal zone B-cell lymphoma (MZL) continue to evolve. Localized MZL responds favorably to local treatments, including surgery and/or local radiation therapy. However, MZL manifests as a disseminated disease in one-third of the cases at diagnosis. Moreover, relapses involving dista...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-009-9260-6
更新日期:2010-04-01 00:00:00
abstract::Fifteen patients with advanced, cisplatin-refractory germ cell tumors (GCT) were treated with iproplatin (CHIP). No objective responses were noted in any of the patients treated. By restricting the entry criteria to heavily pre-treated patients, the identification of new active agents in phase II trials may be hindere...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00944190
更新日期:1992-11-01 00:00:00
abstract::Antiprogestins have been largely utilized in reproductive medicine, yet their repositioning for oncologic use is rapidly emerging. In this study we investigated the molecular mediators of the anti-ovarian cancer activity of the structurally related antiprogestins RU-38486, ORG-31710 and CDB-2914. We studied the respon...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9655-z
更新日期:2012-06-01 00:00:00
abstract::Pharmacological intervention to reduce CRC mortality entails the use of oral agents that can avert carcinogenesis. Silibinin, a major component of silymarin isolated from Silybum marianum (L.) was found to possess attractive remedial features. An in vivo study was designed to elucidate the effect of silibinin on the f...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9237-5
更新日期:2010-06-01 00:00:00
abstract::Mitonafide is the lead compound of a new series of antitumor drugs, the 3-Nitronaphthalimides, which have shown antineoplastic activity in vitro as well as in vivo. This phase I Mitonafide study in non-small cell lung cancer using a 120-hour continuous infusion (120 h. C.I.) schedule of administration was designed to ...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00877242
更新日期:1992-08-01 00:00:00
abstract::We performed a single-institution phase II study to evaluate the efficacy and toxicities of vinorelbine monotherapy in patients previously treated with anthracyclines and taxanes. Vinorelbine was administered at a dose level of 25 mg/m² intravenously on days 1, 8, 15 and 22, every four weeks, and responses were assess...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9357-y
更新日期:2011-04-01 00:00:00
abstract::Cancer is one of the major causes of death for non-transmissible chronic diseases worldwide. Conventional treatments including surgery, chemotherapy and external beam radiotherapy are generally far from curative. Complementary therapies are attempted for achieving more successful treatment response. Systemic targeted ...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/s10637-011-9758-6
更新日期:2012-10-01 00:00:00
abstract::This dose-escalating phase I clinical trial was designed to determine the recommended dose (RD) and to assess the safety and feasibility of weekly plitidepsin (1-hour i.v. infusion, Days 1, 8 and 15) combined with carboplatin (1-hour i.v. infusion, Day 1, after plitidepsin) in 4-week (q4wk) cycles given to patients wi...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9488-1
更新日期:2011-12-01 00:00:00
abstract::A phase II trial of gemcitabine (Gemzar), a nucleoside analogue with broad activity in solid tumors, was performed in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. A total of 26 eligible patients were registered to receive a dose of 1250 mg/m2 weekly for 3 weeks, followed by a 1 w...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/a:1010657609609
更新日期:2001-01-01 00:00:00
abstract::3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or g...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00198593
更新日期:1990-11-01 00:00:00
abstract::Twenty-six patients with advanced, measurable epithelial carcinoma of the ovary were treated with 76 courses of esorubicin at doses ranging from 20-30 mg/m2 every 3 weeks. All patients are evaluable for toxicity and response. All patients had received prior therapy including radiation therapy in 9, non-anthracycline c...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00173763
更新日期:1989-11-01 00:00:00
abstract::This study aimed to analyze the oncology "drug lag" (i.e., the delay in time required for the approval of oncology drugs) in Japan compared with that in the United States of America (US) or the European Union (EU) and to identify the factors associated with this lag. Using publicly available information, we collected ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9638-0
更新日期:2011-08-01 00:00:00
abstract::Adrenocortical carcinoma (ACC) is an aggressive endocrine cancer with few molecular predictors of malignancy and survival, especially in paediatric patients. Stathmin 1 (STMN1) regulates microtubule dynamics and has been involved in the malignant phenotype of cancer cells. Recently, it was reported that STMN1 is highl...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-019-00846-9
更新日期:2020-06-01 00:00:00
abstract:OBJECTIVE:The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has received considerable attention as a first-line treatment of advanced colorectal cancers. Difficulties associated with effectively monitoring the activity of this drug have prompted us to seek a pharmacodynamic marker suitable for def...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9817-7
更新日期:2013-02-01 00:00:00