Abstract:
PURPOSE:Preclinical and clinical data support the study of polar-planar compounds such as N-Methylformamide (NMF) in advanced squamous cell carcinoma of the uterine cervix (SCC). This phase II trial sought to determine the efficacy and toxicities of NMF in patients with advanced SCC. PATIENTS AND METHODS:Eligibility for this trial required bidimensionally measurable squamous or adenosquamous cell cancer of the uterine cervix incurable by surgery or radiation therapy, ECOG performance status of < or = 2, no prior NMF and no more than one prior chemotherapy regimen. Patients received NMF at 2000 mg/m2 intravenously over 15-30 minutes days 1, 8 and 15. The cycle was repeated every 42 days. A single dose escalation of 25%, 500 mg/m2 was made after the first cycle if the toxicities did not exceed grade I for hepatic toxicity and grade II for nausea and vomiting. RESULTS:From July 1987 through September 1998, 21 patients with advanced squamous cell carcinoma of the uterine cervix were entered on study. Two patients were ineligible because there was no pretreatment SGOT on one and the other deteriorated prior to drug approval. Therefore, 19 patients were include in the analysis of response and survival. Four were inevaluable, three due to inappropriate tumor evaluation and one secondary to grade III vomiting, who went off study. These patients were included in the denominator while computing the results. There were 2 deaths, one due to pulmonary hemorrhage from perforation during central venous insertion and one due to disease. 30% (6/19) patients had toxicities, Eastern Cooperative Oncology Group (ECOG) grade III or higher and 2 of these patients suffered multiple grade III toxicities. There were no complete or partial responses. CONCLUSION:In this population, NMF in the dose and schedule employed exhibited no clinical activity.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Rajdev L,Yu ZF,Wadler S,Weller E,Kahn SB,Tormey D,Skeel R,Wiernik PHdoi
10.1023/a:1010672618269subject
Has Abstractpub_date
2001-01-01 00:00:00pages
233-7issue
3eissn
0167-6997issn
1573-0646journal_volume
19pub_type
临床试验,杂志文章,多中心研究abstract::As HER2 is a client protein of the molecular chaperone Hsp90, targeting Hsp90 may be beneficial in HER2-positive breast cancer. In this study, the activity of the Hsp90 inhibitor NVP-AUY922 was assessed in HER2 overexpressing breast cancer cell lines, including two cell line models of acquired trastuzumab-resistance. ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0556-7
更新日期:2018-08-01 00:00:00
abstract::The novel oral antiangiogenic agent TSU-68 was investigated in patients with metastatic breast cancer. Patients with anthracycline-pretreated metastatic breast cancer were randomly assigned to receive either TSU-68 400 mg twice daily on days 1-21 plus docetaxel 60 mg/m(2) on day 1 every 3 weeks, or docetaxel 60 mg/m(2...
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/s10637-014-0093-6
更新日期:2014-08-01 00:00:00
abstract::Receptor tyrosine kinases (RTKs) modulate a variety of cellular events, including cell proliferation, differentiation, mobility and apoptosis. In addition, RTKs have been validated as targets for cancer therapies. Microtubules are another class of proven targets for many clinical anticancer drugs. Here, we report that...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9577-1
更新日期:2012-04-01 00:00:00
abstract::Ninhydrin (2,2-dihydroxy-1,3-indane dione) was evaluated for its antitumor and cytotoxic properties in Ehrlich ascites carcinoma cell (EAC Cell)-bearing mice. The rationale behind this study has been mainly the literature reports of its characteristic interference with DNA synthesis and calcium homeostasis. Antitumor ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/a:1006465504723
更新日期:2000-08-01 00:00:00
abstract::Certain toxic effects of cytotoxic anticancer agents typically evolve over weeks. When such agents are administered weekly, these effects are cumulative. With such schedules, good medical practice mandates dose modifications with mild or moderate toxicity in order to avoid progression to serious or life-threatening to...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/a:1025464510639
更新日期:2003-08-01 00:00:00
abstract:PURPOSE:BMS-275183 is an oral C-4 methyl carbonate analogue of paclitaxel that has the same mechanism of action, stabilization of tubulin polymerization. The present study was designed to: (i) assess the safety and tolerability of BMS-275183, and (ii) determine a suitable Phase II dose of BMS-275183 when given on a con...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-010-9498-z
更新日期:2011-12-01 00:00:00
abstract::Menogaril, a semisynthetic anthracycline antibiotic, was administered to patients with metastatic adenocarcinoma of the prostate. Forty-five patients with measurable disease and 45 patients with evaluable disease received 150-200 mg/m2 over 1 hour every 28 days. There were three partial responses (PR) among 87 patient...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/BF00873240
更新日期:1994-01-01 00:00:00
abstract:BACKGROUND:TAS-102 is a nucleoside antitumor agent consisting of trifluridine (FTD) and tipiracil hydrochloride (TPI). We investigated the recommended dose (RD) of TAS-102 plus irinotecan for metastatic colorectal cancer refractory to 5-fluorouracil (5-FU) and oxaliplatin. METHODS:This study was used a escalated dose ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-015-0271-1
更新日期:2015-10-01 00:00:00
abstract::Idarubicin, a new analogue of daunorubicin, was administered to 27 patients with advanced breast cancer in a phase II trial. The drug was given orally at a dose of 30-35 mg/m2 every 3 weeks. Twenty-two patients were evaluable for response. All evaluable patients were previously treated with one or more chemotherapeuti...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00172014
更新日期:1986-01-01 00:00:00
abstract::XK469 (NSC 656889) is a water-soluble member of the novel quinoxaline family of antitumor agents. In vitro, XK469 demonstrated selective cytotoxicity for several murine solid tumors including colorectal and mammary adenocarcinoma cell lines, when compared to both leukemia and normal epithelial cells. In vivo, XK469 wa...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/a:1006206814025
更新日期:1998-01-01 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:BACKGROUND:Although its efficacy is unproven, 5-fluorouracil plus cisplatin (FP) is used to prevent postoperative relapse in gastric cancer. We investigated the safety and feasibility of S-1 plus cisplatin (SP) vs. FP for stage IIIB-IV (M0) gastric cancer. METHODS:Following curative resection, 41 stage IIIB-IV (M0) ga...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9515-2
更新日期:2012-02-01 00:00:00
abstract::The poor prognosis of children with high-grade glioma (HGG) and high-risk neuroblastoma, despite multidisciplinary therapeutic approaches, demands new treatments for these indications. F14512 is a topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells via the Polyamine...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-014-0132-3
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:To explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology. METHODS:Patients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study of lapatinib 1,500 mg PO daily....
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/s10637-010-9541-0
更新日期:2012-04-01 00:00:00
abstract:PURPOSE:Vorinostat (V) at levels >2.5 µM enhances chemotherapy in vitro. Yet the approved oral dose of 400 mg inconsistently achieves this level in patients. We developed an intermittent oral pulse-dose schedule of V to increase serum levels. We combined V with the cyclin dependent kinase inhibitor flavopiridol (F) whi...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9447-x
更新日期:2011-10-01 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: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::Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic melanoma and other cancers and have shown promising results. Inhibition of CTLA-4 characteristically induces well-known side effects called "immune-related adverse ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-014-0092-7
更新日期:2014-08-01 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::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::Angiogenesis is recognized as an important biological process that allows growth of a tumor beyond an initial small size. PTK787/ZK222584, a potent orally active angiogenesis inhibitor capable of inhibiting all known isoforms of Vascular Endothelial Growth Factor (VEGF) receptor, belongs to the class of aminophthalazi...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9157-9
更新日期:2009-02-01 00:00:00
abstract::Pre-clinical and clinical studies have shown that trifluoperazine (TFP) can modulate multidrug resistance. We have performed a Phase II trial of TFP and doxorubicin in doxorubicin-naive patients with metastatic breast cancer. We hypothesized that TFP would inhibit the development of doxorubicin resistance, resulting i...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00873916
更新日期:1993-02-01 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::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::A novel schedule of 5-fluorouracil administration has been developed for biochemical modulation studies. In combination with the pyrimidine synthesis inhibitor PALA, 5-fluorouracil has been given as a 24-hour infusion, repeated weekly: a dose of 2600 mg/m2 is well tolerated. To identify a suitable dose of 5-fluorourac...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00874152
更新日期:1993-05-01 00:00:00
abstract::Purpose The aim of this study is to detect apoptotic and cytotoxic/antiproliferative effects of a ligand substance and its metal derivatives. The substances were investigated by using an h-ras oncogene transformed rat embryo fibroblast cell line (5RP7). Methods The cytotoxic influences of dipyrido[3,2-a:2',3'c]phenazi...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0559-4
更新日期:2018-10-01 00:00:00
abstract::We have previously described a human pancreatic-ribonuclease variant, named PE5, which carries a non-contiguous extended bipartite nuclear localization signal. This signal comprises residues from at least three regions of the protein. We postulated that the introduction of this signal in the ribonuclease provides it w...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9426-2
更新日期:2011-10-01 00:00:00
abstract::Herein we describe a series of multifunctional 5-aminolevulinic-acid (ALA) prodrugs for photodynamic dependent and independent cancer therapy (PDT). We studied the cell-death mechanisms in glioblastoma U251 cells treated with four ALA-prodrugs: (1) AlaAcBu, that releases ALA, acetaldehyde, and butyric acid; (2) AlaFaB...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9669-6
更新日期:2012-06-01 00:00:00
abstract::Myricetin is a naturally omnipresent benzo-α-pyrone flavonoids derivative; has potent anticancer activity. Receptor tyrosine kinases family provides the decisive role in cancer initiation and progression. These receptors have recently caught the attention of the researchers as an attractive target to combat cancer, ow...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-015-0240-8
更新日期:2015-06-01 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