Abstract：
BACKGROUND:Lactoferrin is an iron-binding glycoprotein first identified in breast milk as a protein product of mammary epithelial cells. Its immunomodulatory functions include activation of NK and lymphokine-activated killer cells and enhancement of PMN and macrophage cytotoxicity. Studies in animal models have shown promising anti-cancer activity. The purpose of the present study was to evaluate the safety and tolerability of talactoferrin alfa (talactoferrin; TLF) in humans, as well as pharmacokinetics and pharmacodynamics. METHODS:Ten adult patients with progressive advanced solid tumors who had failed conventional chemotherapy were administered oral TLF at doses from 1.5 to 9 g/day, using a 2 weeks on, 2 weeks off schedule. Patients were evaluated for drug toxicity, tumor growth rate, talactoferrin pharmacokinetics and cytokine markers. RESULTS:Talactoferrin was very well tolerated. No hematological, hepatic, or renal toxicities were reported. A single patient had Grade 2 diarrhea, and there were no Grade 3 or 4 toxicities. Following oral administration, significant levels of talactoferrin were undetectable in circulation, but a statistically significant increase in circulating IL-18, a pharmacodynamic indicator of talactoferrin activity, was observed. Of the eight patients who were radiologically evaluable, five (63%) had stable disease by RECIST criteria two months after start of therapy, including one patient with a minor response. Seven patients (88%) had a decrease in their tumor growth rate. The three patients with non-small cell lung cancer (NSCLC) all survived for at least one year following the start of talactoferrin monotherapy. CONCLUSIONS:Talactoferrin is a promising, well-tolerated new agent that should be evaluated further in patients with refractory metastatic cancer.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Hayes TG,Falchook GF,Varadhachary GR,Smith DP,Davis LD,Dhingra HM,Hayes BP,Varadhachary Adoi
10.1007/s10637-005-3690-6subject
Has Abstractpub_date
2006-05-01 00:00:00pages
233-40issue
3eissn
0167-6997issn
1573-0646journal_volume
24pub_type
杂志文章abstract：:In this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m2 i.v. followed one day later with mitoxantrone (Novantrone; dihydroxyanthracenedione) 16 mg/m2 i.v. Drug treatment was repeated every 3-4 weeks, for a maximum of 12 cycles. The overall response rate w...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00174165
更新日期：1985-01-01 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：:Trimetrexate (TMTX) is an analog of methotrexate and a potent inhibitor of the enzyme dihydrofolate reductase. In this phase I study, TMTX was given intravenously to 32 patients as a constant infusion over 24 hours every 28 days. The maximum-tolerated dose of TMTX was 200 mg/m2, with myelosuppression as the dose-limit...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00177251
更新日期：1990-05-01 00:00:00
abstract：BACKGROUND:Alterations in retinoid signaling appear to be involved in the pathogenesis of small cell lung cancer (SCLC). Fenretinide [N-(4-hydroxyphenyl)retinamide], a synthetic retinoid, inhibits the growth of SCLC cells in vitro via the induction of apoptosis. Since these data suggested that SCLC is the adult solid t...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-009-9228-6
更新日期：2009-12-01 00:00:00
abstract：:Gemcitabine is a deoxycytidine (dCyd) analog with activity in leukemia and solid tumors, which requires phosphorylation by deoxycytidine kinase (dCK). Decreased membrane transport is a mechanism of resistance to gemcitabine. In order to facilitate gemcitabine uptake and prolong retention in the cell, a lipophilic pro-...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-009-9377-7
更新日期：2011-06-01 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：:Tyrosine kinase inhibitors (TKI) or monoclonal antibodies targeting EGFR, HER2 or VEGFR receptors have demonstrated substantial clinical benefit in patients with advanced breast cancer, colon cancer, head and neck cancer, non-small cell lung cancer, and renal cell carcinoma. Nevertheless, these drugs have some target ...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-009-9252-6
更新日期：2010-06-01 00:00:00
abstract：:Radioactive iodine-refractory [(18)F] fluorodeoxy-glucose-positron emission tomography-positive thyroid carcinomas represent especially aggressive tumors. Targeting glucose metabolism by the transketolase isoenzyme transketolase like 1 (TKTL-1) which is over-expressed in various neoplasms, may be effective. The correl...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-008-9174-8
更新日期：2009-08-01 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：:The population approach has been implemented prospectively in the clinical development of docetaxel (Taxotere). Overall 640 patients were evaluable for the population PK/PD analysis. The PK analysis evidenced significant covariates explaining the inter-patient variability of docetaxel clearance and the PK/PD analysis ...
journal_title：Investigational new drugs
pub_type： 杂志文章,评审
doi：10.1023/a:1010687017717
更新日期：2001-05-01 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 This Phase 1b study aimed to determine the recommended Phase 2 dose of LY2334737, an oral pro-drug of gemcitabine, in combination with capecitabine, an oral pro-drug of 5-fluorouracil, in patients with advanced solid tumors. In addition, pharmacokinetics (PK) and tumor response were evaluated. Patients and ...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-015-0207-9
更新日期：2015-04-01 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：:Menogarol is a new anthracycline undergoing phase I clinical trial. We report here the lethality after 2 hr exposure to 2 drug combinations of menogarol and several antitumor agents. A new statistical procedure was used to identify synergistic combinations. Most of these combinations were additive, except for menogaro...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00179427
更新日期：1985-01-01 00:00:00
abstract：BACKGROUND AND RATIONALE:Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitin-proteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. METHODS:The primary endpoi...
journal_title：Investigational new drugs
pub_type： 杂志文章,多中心研究
doi：10.1007/s10637-010-9532-1
更新日期：2012-02-01 00:00:00
abstract：AIM:To quantify the effect of food on the systemic exposure of lapatinib at steady state when administered 1 h before and after meals, and to observe the safety and tolerability of lapatinib under these conditions in patients with advanced solid tumours. METHODS:This was a three-treatment, randomised, three-sequence c...
journal_title：Investigational new drugs
pub_type： 杂志文章,随机对照试验
doi：10.1007/s10637-013-0055-4
更新日期：2014-06-01 00:00:00
abstract：:An inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that typically develops in the lungs and seldom in the head and neck region. It is often related to the anaplastic lymphoma kinase (ALK) fusion gene. Crizotinib, a first-generation ALK inhibitor, has been shown to have a notable response in pat...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-019-00742-2
更新日期：2019-08-01 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：:The modulation of intracellular nuclear factor-kappaB (NF-κB) signaling pathway involved in the deregulated expression of cell proliferation and cell cycle regulatory molecules is a pragmatic approach for chemoprevention. Eugenol (4-allyl-1-hydroxy-2-methoxybenzene), a natural phenolic constituent of oils of cloves is...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-009-9345-2
更新日期：2011-02-01 00:00:00
abstract：:Breast cancer is commonly treated with anti-estrogens or aromatase inhibitors, but resistant disease eventually develops and new therapies for such resistance are of great interest. We have previously isolated several tamoxifen-resistant variant sub-lines of the MCF-7 breast cancer cell line and provided evidence that...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-011-9768-4
更新日期：2012-12-01 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：:Flavone acetic acid (FAA) was incubated for 1 to 48 hr with 3 established human colon cancer cell lines endowed with distinct degrees of phenotypic properties. All 3 lines responded to FAA in almost identical fashion; when incubated with the drug for only 1 hr, an initial decrease in survival was observed for concentr...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00173501
更新日期：1986-01-01 00:00:00
abstract：:4-demethoxydaunorubicin (4-dm DNR), a new analog of daunorubicin, was tested at an every 3-week dose schedule in 63 evaluable patients with various forms of disseminated malignancy. Utilizing the intravenous (i.v.) route of administration, the maximum tolerated dose (MTD) was 15-18 mg/m2; with the oral route the MTD w...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00172075
更新日期：1983-01-01 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：PURPOSE:Vincristine sulfate liposomes injection (VSLI, Marqibo®) is an FDA approved encapsulated preparation of standard vincristine in sphingomyelin/cholesterol liposomes. Clinical pharmacokinetics show VSLI to be a long-circulating, slow release formulation that is confined to plasma, and prior data on cerebrospinal ...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-015-0311-x
更新日期：2016-02-01 00:00:00
abstract：:Hexamethylenebisacetamide (HMBA), an in vitro differentiating agent, was studied for its pharmacodynamic actions in animals. Plasma stability, organ distribution, excretion, oral bioavailability, and estimates of pharmacokinetic parameters and acute lethality were determined in rats. The single dose intraperitoneal LD...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00179430
更新日期：1985-01-01 00:00:00
abstract：:Nafazatrom was tested against a variety of human malignancies with the human tumor stem cell assay at one or more of the following concentrations: 1, 10, 25, and 100 micrograms/ml X 1 h or 0.05, 0.5, or 5 micrograms/ml by continuous exposure. Major (greater than or equal to 70%) inhibition was noted in 7/52 adenocarci...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00173781
更新日期：1984-01-01 00:00:00
abstract：:Fluorinated pyrimidines, particularly 5-fluorouracil (FUra), have been the subject of intense and almost continuous basic and clinical study since development in the late 1950's by Dr. Charles Heidelberger. Despite this intensive effort, the most important mechanisms by which FUra influences tumor growth in individual...
journal_title：Investigational new drugs
pub_type： 杂志文章,评审
doi：10.1007/BF00178188
更新日期：1989-04-01 00:00:00
abstract：:A new anthracycline derivative, SM5887, in combination with commonly used anticancer agents was evaluated against T-cell leukemia MOLT-3 and human osteosarcoma MG-63 cell lines in culture. MOLT-3 and MG-63 cells were incubated with various concentrations of 13-hydroxy SM5887 (SM5887-OH, the active metabolite of SM5887...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00180811
更新日期：1996-01-01 00:00:00
abstract：:Fifteen patients with advanced carcinoma of the breast who had failed prior chemotherapy, were treated with recombinant gamma interferon at a dose of 2mg/m2 (1mg = 2.4 X 10(7) international units) intravenously for five consecutive days every other week. The median patient age was 51 and all patients had a performance...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00173511
更新日期：1986-01-01 00:00:00
