Phase II study of didemnin B in advanced colorectal cancer.

Abstract:

:Didemnin B is a depsipeptide derived from a Caribbean tunicate (sea squirt) that has demonstrated antineoplastic activity against a variety of murine tumor models, including the L1210 and P388 leukemia, the B16 melanoma, and M5076 sarcoma cell lines. Based on these data, we designed a phase II trial in which 15 patients with measurable, unresectable colorectal cancer were treated with Didemnin B at an initial dosage of 3.47 mg/m2 over 30 minutes administered by intravenous infusion every 28 days; the dosage was altered in accordance with the toxicity observed, with only one patient requiring a dosage reduction for pronounced nausea and vomiting. No hematologic or nonhematologic toxicity developed. No complete or partial responses were observed. These results do not compare favorably with results of treatments using other single agents or combinations that are currently available for the treatment of advanced colorectal cancers. However, because of the tolerable levels of toxicity experienced by in our patients, it is possible that an insufficient dose of the medication was delivered. We concluded that Didemnin B is not active against of colorectal cancers at the dosage and schedule at which it was administered in this study.

journal_name

Invest New Drugs

authors

Jones DV Jr,Ajani JA,Blackburn R,Daugherty K,Levin B,Patt YZ,Abbruzzese JL

doi

10.1007/BF00877248

subject

Has Abstract

pub_date

1992-08-01 00:00:00

pages

211-3

issue

3

eissn

0167-6997

issn

1573-0646

journal_volume

10

pub_type

临床试验,杂志文章
  • Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplifi

    abstract::Neuroblastoma is an extracranial, solid, and heterogeneous malignancy in children. The conventional therapeutic modalities are mostly ineffective and thus new therapeutic strategies for malignant neuroblastoma are urgently warranted. We examined the synergistic efficacy of combination of sorafenib (SF) and genistein (...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-009-9324-7

    authors: Roy Choudhury S,Karmakar S,Banik NL,Ray SK

    更新日期:2010-12-01 00:00:00

  • Phase I study of 4-demethoxydaunorubicin.

    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

    authors: Bonfante V,Ferrari L,Villani F,Bonadonna G

    更新日期:1983-01-01 00:00:00

  • A phase II randomized study of cetuximab and bevacizumab alone or in combination with gemcitabine as first-line therapy for metastatic pancreatic adenocarcinoma.

    abstract::The purpose of this study was to assess the efficacy and safety of bevacizumab plus cetuximab with or without gemcitabine in patients with advanced pancreatic adenocarcinoma. Patients with locally advanced or metastatic pancreatic adenocarcinoma, previously untreated, were randomized to bevacizumab (10 mg/kg q2w) plus...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s10637-011-9691-8

    authors: Ko AH,Youssoufian H,Gurtler J,Dicke K,Kayaleh O,Lenz HJ,Keaton M,Katz T,Ballal S,Rowinsky EK

    更新日期:2012-08-01 00:00:00

  • A phase I and pharmacokinetic study of trimetrexate using a 24-hour continuous-injection schedule.

    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

    authors: Allegra CJ,Jenkins J,Weiss RB,Balis F,Drake JC,Brooks J,Thomas R,Curt GA

    更新日期:1990-05-01 00:00:00

  • Absolute and relative activities of platinum-complexes on human tumors as evaluated by an antimetabolic in vitro assay.

    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

    authors: Daidone MG,Silvestrini R,Zaffaroni N,Grignolio E,Landoni F

    更新日期:1987-01-01 00:00:00

  • Preliminary pharmacokinetic and bioanalytical studies of SJG-136 (NSC 694501), a sequence-selective pyrrolobenzodiazepine dimer DNA-cross-linking agent.

    abstract::SJG-136 is a synthetic pyrrolobenzodiazepine (PBD) dimer in which two DNA-alkylating subunits are linked through an inert propanedioxy tether. Biophysical and biochemical studies of SJG-136 have shown a remarkable affinity for DNA and potent cytotoxicity in vitro. On this basis, together with its unique sequence selec...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1023/B:DRUG.0000026249.97007.60

    authors: Wilkinson GP,Taylor JP,Shnyder S,Cooper P,Howard PW,Thurston DE,Jenkins TC,Loadman PM

    更新日期:2004-08-01 00:00:00

  • Sequential studies on the role of mitoxantrone in the treatment of acute leukemia.

    abstract::Mitoxantrone (Novantrone; 1, 4-dihydroxy-5, 8-bis [[2-[(2-hydroxyethyl) amino]ethyl]amino-] 9, 10 anthracenedione dihydrochloride (NSC 301739] is a synthetic anthracenedione with intercalating properties. Activity has been shown in preclinical studies in mice bearing intraperitoneal P388 and L1210 leukaemias, ADJ-Pc6 ...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00174172

    authors: Prentice HG,Wimperis JZ,Robbins G

    更新日期:1985-01-01 00:00:00

  • Phase II trial of PCNU in breast carcinoma.

    abstract::The Eastern Cooperative Oncology Group undertook a limited institution phase II study of PCNU in advanced, metastatic breast cancer. The study was limited to patients treated with 1 to 2 prior chemotherapy regimens. Accrual goals were 30 patients but the study was terminated after 10 patients had no response, with a r...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00170866

    authors: Rubins JM,Taylor SG 4th

    更新日期:1989-07-01 00:00:00

  • A sensitive docetaxel assay in plasma by solid-phase extraction and high performance liquid chromatography-UV detection: validation and suitability in phase I clinical trial pharmacokinetics.

    abstract::We have developed a specific and sensitive method aiming at docetaxel (Taxotere) determination in plasma of treated patients. This involved solid-phase extraction of 1 ml of plasma onto carboxylic acid (CBA) grafted silica cartridges followed by reversed-phase liquid chromatography with UV detection. The best selectiv...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1006327302041

    authors: Ardiet CJ,Tranchand B,Zanetta S,Guillot A,Bernard E,Peguy M,Rebattu P,Droz JP

    更新日期:1999-01-01 00:00:00

  • Enhanced oncolysis mediated by Coxsackievirus A21 in combination with doxorubicin hydrochloride.

    abstract::Virotherapy is an emerging strategy for the treatment of cancer that utilizes both replication-competent and genetically modified viruses to selectively kill tumor cells. We have previously shown that Coxsackievirus A21 (CVA21), a common-cold producing enterovirus, is an effective oncolytic agent against human melanom...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-010-9614-0

    authors: Skelding KA,Barry RD,Shafren DR

    更新日期:2012-04-01 00:00:00

  • Antiproliferative activity, mechanism of action and oral antitumor activity of CP-4126, a fatty acid derivative of gemcitabine, in in vitro and in vivo tumor models.

    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

    authors: Bergman AM,Adema AD,Balzarini J,Bruheim S,Fichtner I,Noordhuis P,Fodstad O,Myhren F,Sandvold ML,Hendriks HR,Peters GJ

    更新日期:2011-06-01 00:00:00

  • Phase I trial of docetaxel given every 3 weeks and daily lenalidomide in patients with advanced solid tumors.

    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

    authors: Sanborn SL,Gibbons J,Krishnamurthi S,Brell JM,Dowlati A,Bokar JA,Nock C,Horvath N,Bako J,Remick SC,Cooney MM

    更新日期:2009-10-01 00:00:00

  • Discovery of oxyepiberberine as a novel tubulin polymerization inhibitor and an anti-colon cancer agent against LS-1034 cells.

    abstract::Coptis chinensis Franch. has been extensively used in traditional Chinese medicine. The chemical structure of oxyepiberberine, as an alkaloid isolated from Coptis chinensis Franch., has been previously studied. However, anti-cancer effects and underlying mechanisms of oxyepiberberine need to be explored. This study ai...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-020-01006-0

    authors: Ning H,Lu W,Jia Q,Wang J,Yao T,Lv S,Li Y,Wen H

    更新日期:2020-09-30 00:00:00

  • Nafazatrom: clonogenic in-vitro assessment of activity against human malignancies.

    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

    authors: Haas CD,Kyle GW,Crissman JD,Schaldenbrand MF

    更新日期:1984-01-01 00:00:00

  • Durable response to the ALK inhibitor alectinib in inflammatory myofibroblastic tumor of the head and neck with a novel SQSTM1-ALK fusion: a case report.

    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

    authors: Honda K,Kadowaki S,Kato K,Hanai N,Hasegawa Y,Yatabe Y,Muro K

    更新日期:2019-08-01 00:00:00

  • Phase I study of Tomudex and Doxorubicin in patients with locally advanced, inoperable or metastatic cancer (IND.98).

    abstract:BACKGROUND:The primary objective of this Phase I study was to determine the maximum tolerated dose (MTD) and recommended phase II dose for Tomudex and Doxorubicin when given in combination to patients with advanced metastatic cancer. The secondary objective was to assess the toxicity profile. PATIENTS AND METHODS:Star...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/B:DRUG.0000047105.38511.2a

    authors: Bjarnason GA,Charpentier D,Wong R,Goel R,Douglas L,Walsh W,Matthews S,Dent S,Seymour L,Winquist E

    更新日期:2005-01-01 00:00:00

  • Cytotoxicity of anthraquinones from the roots of Pentas schimperi towards multi-factorial drug-resistant cancer cells.

    abstract:INTRODUCTION:Multidrug resistance in cancer represents a major problem in chemotherapy. The present study was designed to assess the cytotoxicity of anthraquinones from Pentas schimperi, namely damnacanthal (1), damnacanthol (2), 3-hydroxy-2-hydroxymethyl anthraquinone (3) and schimperiquinone B (4) against nine drug-s...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-015-0268-9

    authors: Kuete V,Donfack AR,Mbaveng AT,Zeino M,Tane P,Efferth T

    更新日期:2015-08-01 00:00:00

  • A phase I trial of combination trastuzumab, lapatinib, and bevacizumab in patients with advanced cancer.

    abstract:PURPOSE:Preclinical data indicate that combination HER2-directed and anti-VEGF therapy may bypass resistance to trastuzumab. A phase I trial was performed to assess safety, activity, and correlates. EXPERIMENTAL DESIGN:Patients with advanced, refractory malignancy were enrolled (modified 3 + 3 design with expansions f...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-014-0173-7

    authors: Falchook GS,Moulder S,Naing A,Wheler JJ,Hong DS,Piha-Paul SA,Tsimberidou AM,Fu S,Zinner R,Janku F,Jiang Y,Huang M,Parkhurst KL,Kurzrock R

    更新日期:2015-02-01 00:00:00

  • Phase I studies of weekly administration of cytotoxic agents: implications of a mathematical model.

    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

    authors: McClish DK,Roberts JD

    更新日期:2003-08-01 00:00:00

  • Using the neurotransmitter serotonin to target imaging agents to glioblastoma cells.

    abstract::The neurotransmitter serotonin is involved in numerous bodily functions via seven different serotonin receptor subfamilies. Serotonin plays a role in gastrointestinal functions like intestinal secretion or peristalsis and neuropsychiatric events like depression or migraine. One of these subtypes has been found on glio...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-011-9781-7

    authors: Sturzu A,Sheikh S,Klose U,Echner H,Kalbacher H,Deeg M,Nägele T,Horger M,Ernemann U,Heckl S

    更新日期:2012-12-01 00:00:00

  • Cyclodextrin polymers decorated with RGD peptide as delivery systems for targeted anti-cancer chemotherapy.

    abstract::Polymeric cyclodextrin-based nanoparticles are currently undergoing clinical trials as nanotherapeutics. Using a non-covalent approach, we decorated two cross-linked cyclodextrin polymers of different molecular weights with an RGD peptide derivative to construct a novel carrier for the targeted delivery of doxorubicin...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-018-0711-9

    authors: Viale M,Tosto R,Giglio V,Pappalardo G,Oliveri V,Maric I,Mariggiò MA,Vecchio G

    更新日期:2019-08-01 00:00:00

  • Sunitinib inducing tumor lysis syndrome in a patient treated for renal carcinoma.

    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

    authors: Michels J,Lassau N,Gross-Goupil M,Massard C,Mejean A,Escudier B

    更新日期:2010-10-01 00:00:00

  • Multifunctional 5-aminolevulinic acid prodrugs activating diverse cell-death pathways.

    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

    authors: Berkovitch-Luria G,Weitman M,Nudelman A,Rephaeli A,Malik Z

    更新日期:2012-06-01 00:00:00

  • A phase I clinical trial of prolonged infusion of hydroxyurea in combination with hyperfractionated, accelerated, external radiation therapy in patients with advanced squamous cell cancer of the head and neck.

    abstract:BACKGROUND:Preclinical data suggested that sustained inhibition of the anabolic enzyme, ribonucleotide reductase (RR), by hydroxyurea (HU) may be critical for the anticancer effects of the drug. A phase I trial of continuous infusion HU with concomitant hyperfractionated, accelerated radiation therapy (CHU-CHRT) was in...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1006102716920

    authors: Beitler JJ,Smith RV,Haynes H,Silver CE,Quish A,Kotz T,Serrano M,Brook A,Wadler S

    更新日期:1998-01-01 00:00:00

  • Effects of the tumor vasculature targeting agent NGR-TNF on the tumor microenvironment in murine lymphomas.

    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

    authors: van Laarhoven HW,Gambarota G,Heerschap A,Lok J,Verhagen I,Corti A,Toma S,Gallo Stampino C,van der Kogel A,Punt CJ

    更新日期:2006-01-01 00:00:00

  • A phase 1 dose-escalating study of pegylated recombinant human arginase 1 (Peg-rhArg1) in patients with advanced hepatocellular carcinoma.

    abstract:BACKGROUND:Hepatocellular carcinoma (HCC) cells are auxotrophic for arginine, depletion of which leads to tumour regression. The current study evaluated safety, pharmacokinetics (PK)/ pharmacodynamics (PD) parameters, and potential anti-tumor activity of pegylated recombinant human arginase 1 (peg-rhArg1) in advanced H...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9807-9

    authors: Yau T,Cheng PN,Chan P,Chan W,Chen L,Yuen J,Pang R,Fan ST,Poon RT

    更新日期:2013-02-01 00:00:00

  • Perifosine selectively induces cell cycle block and modulates retinoblastoma and E2F1 protein levels in p53 mutated leukemic cell lines.

    abstract::The effect of the single-chain alkylphospholipid perifosine was analyzed in p53(wild-type) (SKW6.4, OCI and MOLM), p53(mutated) (BJAB, MAVER) and p53(null) (HL-60) leukemic cell lines. Perifosine promoted cytotoxicity with a combination of apoptosis induction in all cell lines and cell cycle block at the G(2)M checkpo...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-009-9370-1

    authors: Celeghini C,Voltan R,Rimondi E,Gattei V,Zauli G

    更新日期:2011-04-01 00:00:00

  • A pilot study of S-1 plus cisplatin versus 5-fluorouracil plus cisplatin for postoperative chemotherapy in histological stage IIIB-IV (M0) gastric cancer.

    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

    authors: Lee SS,Jeung HC,Chung HC,Noh SH,Hyung WJ,Ahn JY,Rha SY

    更新日期:2012-02-01 00:00:00

  • Schedule-dependent inhibition of T-cell lymphoma cells by cotreatment with the mTOR inhibitor everolimus and anticancer drugs.

    abstract:OBJECTIVE:Everolimus (RAD001) is a novel mammalian target of rapamycin (mTOR) inhibitor, and anti-proliferative activity in various malignancies has been reported. This study evaluated the anti-tumor effects and schedule-dependent synergism of everolimus in combination with other chemotherapeutic agents in T-cell lymph...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-010-9558-4

    authors: Huang JJ,Li ZM,Huang Y,Huang Y,Tian Y,He XX,Xiao J,Lin TY

    更新日期:2012-02-01 00:00:00

  • A study of a different dose-intense infusion schedule of phenylacetate in patients with recurrent primary brain tumors consortium report.

    abstract:PURPOSE:To compare two different infusion schedules of phenylacetate (PA) in patients with primary brain tumors and to assess the feasibility of the administration in a multi-institutional setting. PATIENTS AND METHODS:Adult patients with recurrent primary brain tumors were treated with PA on two different schedules. ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1023/a:1026299118067

    authors: Chang SM,Kuhn JG,Ian Robins H,Clifford Schold S,Spence AM,Berger MS,Mehta MP,Pollack I,Gilbert M,Prados MD

    更新日期:2003-11-01 00:00:00