Abstract:
PURPOSE:Pyrazoloacridine (PZA) is an acridine derivative selected for clinical development because of broad pre-clinical antitumor activity and solid tumor selectivity. Phase I evaluations with PZA have demonstrated predictable toxicity and suggested clinical efficacy. A phase II trial in patients with previously untreated advanced pancreatic cancer was conducted. METHODS:PZA was administered at a dose of 750 mg/m2 intravenously over 3 hours every 21 days. Seventeen patients were treated receiving a total of 46 courses of PZA. RESULTS:Of the 15 patients evaluable for response, no responses were observed (0% response rate, 95% confidence interval 0-22%). Major toxicities directly attributable to PZA included moderate neutropenia and mild neurotoxicity. CONCLUSION:PZA at this dose and schedule of administration was inactive in patients with pancreatic carcinoma.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Zalupski MM,Shields AF,Philip PA,Kraut M,LoRusso P,Heilbrun LK,Vaitkevicius Vdoi
10.1023/a:1006087114621subject
Has Abstractpub_date
1998-01-01 00:00:00pages
93-6issue
1eissn
0167-6997issn
1573-0646journal_volume
16pub_type
临床试验,杂志文章abstract::Cribrostatin 6 is a quinone-containing natural product that induces the death of cancer cell lines in culture, and its mechanism of action and scope of activity are unknown. Here we show that cribrostatin 6 has broad anticancer activity, potently inducing apoptotic cell death that is not preceded by any defined cell c...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9390-x
更新日期:2011-08-01 00:00:00
abstract::Fluorouracil (5-FU) plus irinotecan combined with bevacizumab has significant activity in metastatic colorectal cancer (mCRC), but S-1 has become a substitute for continuous infusion of 5-FU and has a very low incidence of hand-foot syndrome. With the S-1 plus irinotecan regimen (SIR), the response rate was 62.5%, and...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9743-0
更新日期:2012-08-01 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::Advances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in AML and mutations in this gene are associated with poor overall survival. AXL plays a role in the ac...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0470-z
更新日期:2017-10-01 00:00:00
abstract::Glioblastoma (GBM), one of the most malignant human neoplasias, responds poorly to current treatment modalities, with temozolomide (TMZ) being the drug most frequently used for its treatment. Tetra-O-methyl Nordihydroguaiaretic Acid (M4N) is a global transcriptional repressor of genes dependent on the Sp1 transcriptio...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9917-4
更新日期:2013-08-01 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:PURPOSE:ZD0473 (AMD473) [cis-amminedichloro(2-methylpyridine) platinum(II)] is a novel platinum agent of proven activity in vitro against a variety of human tumor-derived cell lines even with intrinsic or acquired resistance to CDDP. The aim of this study is to provide the basis for a rational design of ZD0473-based co...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/B:DRUG.0000036682.99818.71
更新日期:2004-11-01 00:00:00
abstract::Pictilisib (GDC-0941) is an oral class I phosphatidylinositol-3-phosphate kinase inhibitor. This phase Ia/Ib study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of pictilisib in monotherapy or in combination with carboplatin-paclitaxel and bevacizumab (CP + BEV) in Japanese patients wit...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-016-0382-3
更新日期:2017-02-01 00:00:00
abstract::Twenty-four evaluable patients with epithelial ovarian cancer resistant to primary therapy, or relapsing after response to initial therapy, were treated with acivicin utilizing a daily X 5 schedule. One patient achieved a partial response lasting five months; the remaining 23 patients showed no objective response. Pro...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00172016
更新日期:1986-01-01 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::The primary objective of this phase I study of LY2780301, a dual p70 S6 kinase and Akt inhibitor, was to determine the recommended phase II dose as a single agent in patients with advanced cancer. Secondary objectives included safety, pharmacokinetic, and pharmacodynamic analyses, and co-clinical analyses in Avatar mo...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-015-0241-7
更新日期:2015-06-01 00:00:00
abstract:PURPOSE:Erlotinib (Tarceva®, OSI-774) is a small molecule inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. As high-grade gliomas frequently show amplification, overexpression and/or mutation of EGFR, this drug has been tested in several clinical trials with glioblastoma patients, but unfortunat...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9569-1
更新日期:2012-04-01 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:PURPOSE:To evaluate the response to oral Etoposide when combined with mesna, ifosfamide, and mitoxantrone in patients with relapsed and/or refractory lymphoma. To evaluate response and its duration after administration of intravenous Etoposide, methylprednisolone, high-dose cytosine arabinoside, and cisplatin (ESHAP) a...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00873962
更新日期:1994-01-01 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::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::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::Thirty-three patients with advanced colorectal carcinoma were entered on a phase II trial of weekly IV aminothiadiazole (175 mg/m2 escalated to 200 mg/m2) with concomitant allopurinol and non-steroidal anti-inflammatory agents (NSAID's). Toxicity was predominantly GI, cutaneous, and chest pain/dyspnea. Twenty-five per...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00873044
更新日期:1994-01-01 00:00:00
abstract::Seventeen patients with small cell lung cancer entered a phase II trial testing the feasibility of adding high dose epirubicin (100-120 mg/m2, day 1) in combination with etoposide (60-80 mg/m2, days 1-5) and cisplatin (70 mg/m2, day 1) courses repeated every three weeks. Complete responders received thoracic (40 Gy) a...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00873130
更新日期:1992-07-01 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::Apoptin is a nonstructural protein encoded by one of the three open reading frames of the chicken anemia virus genome. It has attracted a great deal of interest due to its ability to induce apoptosis in multiple transformed and malignant mammalian cell lines without affecting primary and non-transformed cells. However...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0431-6
更新日期:2017-06-01 00:00:00
abstract::An HPLC analytical method was applied to the determination of plasma concentrations of 5,6-dihydro-5-azacytidine (NSC 264880, DHAC) in two foxhounds after a rapid intravenous infusion of 300 mg/kg DHAC. The dose employed is the mouse equivalent LD10 dose which results in mild reversible toxicity in the dog. The declin...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00180191
更新日期:1983-01-01 00:00:00
abstract::Studies with CGP 41 251 (I), an N-benzoylstaurosporine derivative and PKC-alpha inhibitor, revealed that oral administration of 400 microg/day of the compound to wild type mice on four successive days reversed multi drug resistance (Killion et al. Oncology Research 7: 453-459, 1995). In our study, the same regimen of ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/a:1006260217400
更新日期:1999-01-01 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::Fifteen patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck received a 5 day continuous I.V. infusion of 6-thioguanine repeated every five weeks. Dose limiting toxicity was primarily hematological with grade III/IV leucopenia and thrombocytopenia seen in seven patients. Nausea and vo...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00873122
更新日期:1992-07-01 00:00:00
abstract::N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) follo...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00180821
更新日期:1996-01-01 00:00:00
abstract:AIM:5,6-Dimethylxanthenone-4-acetic acid (DMXAA) (ASA404), a low molecular weight antivascular drug currently in clinical trial, acts both directly on the tumour vascular endothelium and indirectly through the induction of inflammatory cytokines and other vasoactive molecules from macrophages and other host cells. We w...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9167-7
更新日期:2009-06-01 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::We previously found that the novel histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) had greater selectivity against cutaneous T-cell lymphoma (CTCL) than SAHA. AN-7 synergizes with doxorubicin (Dox), an anthracycline antibiotic that induces DNA breaks. This study aimed to elucidate the m...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0500-x
更新日期:2018-02-01 00:00:00
abstract:BACKGROUND:The phase I program of anticancer agents usually consists of multiple dose escalation studies to select a safe dose for various administration schedules. We hypothesized that pharmacokinetic and pharmacodynamic (PK-PD) modeling of an initial phase I study (stage 1) can be used for selection of an optimal sta...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9216-2
更新日期:2010-02-01 00:00:00