Abstract:
:The limiting toxicity of low dose continuous infusion 5-fluorouracil (200-300 mg/m2/day) is often palmar-plantar erythrodysesthesia (PPE). PPE developed in 16/25 patients (exact 95% confidence interval of 42%-82%) with metastatic colon cancer enrolled in a phase II trial. In this trial, 5-FU was given continuously at a dose of 200 mg/m2/day until toxicity or progressive disease forced discontinuation. The first signs of the syndrome developed at a median of 2 months following infusion initiation and, unless treatment was interrupted, became progressively worse. The incidence of moderate to severe PPE was 71% in the 14 previously untreated patients (exact 95% confidence intervals of 42-92%). Seventy-eight percent of the responders in the no prior treatment group developed PPE. The incidence of moderate to severe PPE was only 27% in the 11 previously treated patients (exact 95% confidence intervals of 6-61%). The higher incidence of PPE in the previously untreated patients probably resulted from a longer total infusion time (median = 7.3 months) than the previously treated (median = 4.5 months). The longer infusion time in turn was a result of the higher response rates (64 vs 18%) in the previously untreated versus treated groups. Five previously untreated patients who developed PPE received 50 or 150 mg of pyridoxine/day when moderate PPE changes were noted. Reversal of PPE without interruption of the 5-FU was seen in 4/5 patients. Four of these patients who received pyridoxine had responded to 5-FU treatment. No adverse affect of pyridoxine on clinical response was noted.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Fabian CJ,Molina R,Slavik M,Dahlberg S,Giri S,Stephens Rdoi
10.1007/BF00216925subject
Has Abstractpub_date
1990-02-01 00:00:00pages
57-63issue
1eissn
0167-6997issn
1573-0646journal_volume
8pub_type
杂志文章abstract:BACKGROUND:Based on reports of the efficacy of docetaxel (T) in STS, we undertook a phase I/II trial to determine the response rate (RR), dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of addition of T to doxorubicin (A) and ifosfamide (I) in advanced STS. METHODS:Patients with advanced, recurrent, or ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-006-9035-2
更新日期:2006-11-01 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::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:BACKGROUND:Although bevacizumab plus FOLFOX is a standard treatment for metastatic colorectal cancer, oxaliplatin must be withdrawn in many patients because of cumulative neurotoxicity. We postulated that a reduced dose of oxaliplatin and modified treatment schedule would prolong the time to treatment failure and evalu...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-015-0239-1
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:Docetaxel-prednisone (DP) is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC). Orteronel (TAK-700) is an investigational, selective, non-steroidal inhibitor of 17,20-lyase, a key enzyme in androgenic hormone production. This phase 1/2 study evaluated orteronel plus DP in mCRPC ...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-014-0199-x
更新日期:2015-04-01 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: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:To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and tolerability of MN-209, a novel vascular disrupting agent, in patients with advanced solid tumors. STUDY DESIGN:MN-029 was administered weekly for three consecutive weeks out of four; two cycles were planned. Dose escalation ...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-009-9264-2
更新日期:2010-08-01 00:00:00
abstract::Bombesin/gastrin-releasing peptides (BN/GRP) were shown to bind selectively to cell surface receptors, stimulating the growth of various types of malignancies in murine and human models. The novel BN/GRP synthetic receptor antagonist, RC-3095, was able to produce long-lasting tumor regressions in murine and human tumo...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-006-6886-5
更新日期:2006-09-01 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::Twenty-four patients with acute leukemia or blast crisis (BC) of chronic myelocytic leukemia (CML) in relapse or refractory to standard chemotherapy, were eligible for treatment with mitoxantrone. Mitoxantrone (Novantrone; dihydroxyanthracenedione) was administered in a dose of 8-13 mg/m2 on five consecutive days. Fiv...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00174171
更新日期:1985-01-01 00:00:00
abstract::Background We determined the safety, pharmacokinetics, pharmacodynamics, and antitumour activity of abexinostat in B-cell lymphoma or chronic lymphocytic leukaemia. Patients and methods Thirty-five patients received oral abexinostat 30, 45, or 60 mg/m(2) bid in a 3 + 3 design in three 21-day schedules: 14 days on trea...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-015-0206-x
更新日期:2015-04-01 00:00:00
abstract::Six patients with incurable malignancies were originally treated with vitamin E, 3200 IU/day for fourteen days, followed by the same dose of vitamin E daily plus LCV (20 mg/m2 i.v. bolus daily x 5) with 5FU (425 mg/m2 i.v. bolus immediately following LCV). The same schedule of LCV and 5FU was repeated 4 weeks later, t...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/a:1006484031959
更新日期:2001-01-01 00:00:00
abstract:PURPOSE:Amrubicin is a novel 9-aminoanthracycline. This multicenter phase II study was conducted to evaluate the efficacy and safety of amrubicin in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:Sixty-one previously untreated patients with stage III or IV NSCLC were entered this study. The pat...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s10637-006-5937-2
更新日期:2006-03-01 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::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::Background DR5 is a transmembrane receptor that transduces extracellular ligand-binding to activate apoptosis signaling cascades. This phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of a new monoclonal antibody potent DR5 agonist, DS-8273a, in subjects with advanced solid...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-016-0420-1
更新日期:2017-06-01 00:00:00
abstract::Sixteen patients with stage IV melanoma, who were heavily pretreated, received 11 mg/m2/day of intravenous Irofulven for five consecutive days every 28 days. There were no objective tumor responses, although one patient exhibited stable disease after 4 cycles. The most common toxicities were grade 1/2 nausea, vomiting...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/a:1016261918256
更新日期:2002-08-01 00:00:00
abstract:INTRODUCTION:Heat shock protein 90 (Hsp90) has been studied as a therapeutic target in many cancers. In preclinical trials, the Hsp90 ATPase inhibitor ganetespib demonstrated potent inhibition of solid tumor growth, with superior potency than prior Hsp90 inhibitors. Given the promising preclinical outcome and favorable...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-015-0307-6
更新日期:2016-02-01 00:00:00
abstract::TNF-alpha may improve drug delivery to tumors by alteration of vascular permeability. However, toxicity precludes its systemic administration in patients. NGR-TNF comprises TNF coupled to the peptide CNGRC, which is a ligand for CD13. CD13 is expressed on tumor vasculature. Therefore, to assess the efficacy of NGR-TNF...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-005-4540-2
更新日期:2006-01-01 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::Chemoprevention opens new perspectives in the prevention of cancer and other degenerative diseases. Use of target-organ biological models at the histological and genetic levels can markedly facilitate the identification of potential chemopreventive agents. Our aim was to study the chemopreventive efficacy of pronyl-ly...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9122-7
更新日期:2008-12-01 00:00:00
abstract::CP-4126 is a gemcitabine (2',2'-difluorodeoxycytidine; dFdC) 5' elaidic acid ester. The purpose of this dose-escalating study was to assess safety, pharmacokinetics (PK) and preliminary antitumor activity of the oral formulation and to determine the recommended dose (RD) for phase II studies. The study had a two-step ...
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/s10637-013-9925-z
更新日期:2013-08-01 00:00:00
abstract::Sunitinib is an oral antityrosine kinase inhibitor that has antiangiogenic and antitumor activities. It has been approved for the treatment of advanced RCC and for imatinib-refractory gastrointestinal stromal tumors (GIST). Tumor lysis syndrom can occur in solid tumors. We report a case of patient with metastatic RCC ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9275-z
更新日期:2010-10-01 00:00:00
abstract::In vitro cytotoxicity and xanthine oxidase inhibition capabilities were investigated for five palladium (II) chelate complexes. The palladium complexes were synthesized by starting from S-alkyl-thiosemicarbazones where the alkyl component is methyl, ethyl, propyl or butyl. The solid complexes are characterized by elem...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-019-00751-1
更新日期:2019-12-01 00:00:00
abstract::Background Treatment of recurrent, unresectable granulosa cell tumor (GCT) of the ovary can be challenging. Given the rarity of the tumor, alternative therapies have been difficult to evaluate in large prospective clinical trials. Currently, to our knowledge, there are no reports of the use of immune checkpoint inhibi...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-01043-9
更新日期:2021-01-07 00:00:00
abstract::Bryostatin 1 (Bryo) is a naturally occurring macrocyclic lactone with antineoplastic activity. Like the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) it directly activates the calcium- and phospholipid-dependent protein kinase C (PKC), thus generating a number of different cellular responses. We investigat...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00873230
更新日期:1994-01-01 00:00:00
abstract::Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellula...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9245-5
更新日期:2010-06-01 00:00:00
abstract::Nafazatrom, a synthetic pyrazolinone derivative, has been shown to have substantial antitumor activity in vitro and antitumor and antimetastatic activity in experimental animal systems. The drug has produced no substantial toxicity in preclinical studies and during limited human trials. A phase I clinical trial with t...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00179592
更新日期:1986-01-01 00:00:00
abstract::Introduction BTH1677, a 1,3-1,6 beta-glucan immunomodulator, stimulates a coordinated anti-cancer immune response in combination with anti-tumor antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with cetuximab/carboplatin/paclitaxel in untreated stage ...
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/s10637-017-0450-3
更新日期:2017-06-01 00:00:00