A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors.


:Purpose Preclinical evidence suggests dichloroacetate (DCA) can reverse the Warburg effect and inhibit growth in cancer models. This phase 1 study was undertaken to assess the safety, recommended phase 2 dose (RP2D), and pharmacokinetic (PK) profile of oral DCA in patients with advanced solid tumors. Patients and Methods Twenty-four patients with advanced solid malignancies were enrolled using a standard 3 + 3 protocol at a starting dose of 6.25 mg/kg twice daily (BID). Treatment on 28 days cycles was continued until progression, toxicity, or consent withdrawal. PK samples were collected on days 1 and 15 of cycle 1, and day 1 of subsequent cycles. PET imaging ((18) F-FDG uptake) was investigated as a potential biomarker of response. Results Twenty-three evaluable patients were treated with DCA at two doses: 6.25 mg/kg and 12.5 mg/kg BID (median of 2 cycles each). No DLTs occurred in the 6.25 mg/kg BID cohort so the dose was escalated. Three of seven patients had DLTs (fatigue, vomiting, diarrhea) at 12.5 mg/kg BID. Thirteen additional patients were treated at 6.25 mg/kg BID. Most toxicities were grade 1-2 with the most common being fatigue, neuropathy and nausea. No responses were observed and eight patients had stable disease. The DCA PK profile in cancer patients was consistent with previously published data. There was high variability in PK values and neuropathy among patients. Progressive increase in DCA trough levels and a trend towards decreased (18) F-FDG uptake with length of DCA therapy was observed. Conclusions The RP2D of oral DCA is 6.25 mg/kg BID. Toxicities will require careful monitoring in future trials.


Invest New Drugs


Chu QS,Sangha R,Spratlin J,Vos LJ,Mackey JR,McEwan AJ,Venner P,Michelakis ED




Has Abstract


2015-06-01 00:00:00












  • Phase I study of mitonafide in 120 hour continuous infusion in non-small cell lung cancer.

    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


    authors: Rosell R,Carles J,Abad A,Ribelles N,Barnadas A,Benavides A,Martin M

    更新日期:1992-08-01 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


    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

  • Alterations in human circulating and bone marrow mononuclear cell polyamine levels in hematologic malignancies as a consequence of difluoromethylornithine administration.

    abstract::The effect of administering increasing intravenous doses of difluoromethylornithine on human tumor cell polyamine levels was determined in patients with hematologic malignancies. Difluoromethylornithine from 5.5. to 64 gm/m2 per day was administered to nine patients with refractory acute leukemia or multiple myeloma. ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Maddox AM,Freireich EJ,Keating MJ,Frasier-Scott KF,Haddox MK

    更新日期:1988-06-01 00:00:00

  • Dual modulation of JNK and Akt signaling pathways by chaetoglobosin K in human lung carcinoma and ras-transformed epithelial cells.

    abstract::Chaetoglobosin K (ChK) is a natural product that inhibits anchorage-dependent and anchorage-independent growth of ras-transformed cells, prevents tumor-promoter disruption of cell-cell communication, and reduces Akt activation in tumorigenic cells. This study demonstrates how ChK modulates the JNK pathway in ras-trans...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Ali A,Sidorova TS,Matesic DF

    更新日期:2013-06-01 00:00:00

  • Recombinant human lactoferrin carrying humanized glycosylation exhibits antileukemia selective cytotoxicity, microfilament disruption, cell cycle arrest, and apoptosis activities.

    abstract::Lactoferrin has gained extensive attention due to its ample biological properties. In this study, recombinant human lactoferrin carrying humanized glycosylation (rhLf-h-glycan) expressed in the yeast Pichia pastoris SuperMan5, which is genetically glycoengineered to efficiently produce functional humanized glycoprotei...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Nakamura-Bencomo S,Gutierrez DA,Robles-Escajeda E,Iglesias-Figueroa B,Siqueiros-Cendón TS,Espinoza-Sánchez EA,Arévalo-Gallegos S,Aguilera RJ,Rascón-Cruz Q,Varela-Ramirez A

    更新日期:2020-10-16 00:00:00

  • Tetra-O-methyl nordihydroguaiaretic acid, an inhibitor of Sp1-mediated survivin transcription, induces apoptosis and acts synergistically with chemo-radiotherapy in glioblastoma cells.

    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


    authors: Castro-Gamero AM,Borges KS,Moreno DA,Suazo VK,Fujinami MM,de Paula Gomes Queiroz R,de Oliveira HF,Carlotti CG Jr,Scrideli CA,Tone LG

    更新日期:2013-08-01 00:00:00

  • Multicenter phase II study of amrubicin, 9-amino-anthracycline, in patients with advanced non-small-cell lung cancer (Study 1): West Japan Thoracic Oncology Group (WJTOG) trial.

    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


    authors: Sawa T,Yana T,Takada M,Sugiura T,Kudoh S,Kamei T,Isobe T,Yamamoto H,Yokota S,Katakami N,Tohda Y,Kawakami A,Nakanishi Y,Ariyoshi Y

    更新日期:2006-03-01 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


    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

  • Trimetrexate in advanced carcinoma of the esophagus.

    abstract::Twenty-four patients with advanced epidermoid carcinoma of the esophagus were treated with trimetrexate (TMTX), a lipid soluble non-classical antifol. Patients were given TMTX 8 mg/m2 intravenously day 1-5 every 28 days. In nine of these patients the dose was escalated to 12 mg/m2 day 1-5 every 28 days. Three patients...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Alberts AS,Falkson G,Badata M,Terblanche AP,Schmid EU

    更新日期:1988-12-01 00:00:00

  • Gemcitabine and radiosensitization in human tumor cells.

    abstract::Gemcitabine is a nucleoside analogue with excellent clinical activity against solid tumors. Within the cell, gemcitabine is rapidly phosphorylated to its active di- and triphosphate metabolites. Cytotoxicity with gemcitabine appears to be related to multiple effects on DNA replication, where gemcitabine triphosphate c...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审


    authors: Shewach DS,Lawrence TS

    更新日期:1996-01-01 00:00:00

  • Crizotinib-induced simultaneous multiple cardiac toxicities.

    abstract::Crizotinib is a receptor tyrosine kinase inhibitor that has several targets, including c-ros oncogene 1 and the MET proto-oncogene. Considering its known cardiac toxicity, bradycardia is often investigated following treatment with crizotinib. Our patients had bradycardia, QT prolongation, ventricular rhythm, ventricul...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Oyakawa T,Muraoka N,Iida K,Kusuhara M,Kawamura T,Naito T,Takahashi T

    更新日期:2018-10-01 00:00:00

  • A phase I study of intraperitoneal paclitaxel combined with gemcitabine plus nab-paclitaxel for pancreatic cancer with peritoneal metastasis.

    abstract:PURPOSE:A phase I study of intraperitoneal paclitaxel (ip PTX) combined with gemcitabine (GEM) plus nab-paclitaxel (nab-PTX) (GnP) was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) in pancreatic cancer patients with peritoneal metastasis in first-line setting. METHODS:Based on t...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Takahara N,Nakai Y,Ishigami H,Saito K,Sato T,Hakuta R,Ishigaki K,Saito T,Hamada T,Mizuno S,Kogure H,Yamashita H,Isayama H,Seto Y,Koike K

    更新日期:2020-08-08 00:00:00

  • Phase I trial of neoadjuvant chemoradiotherapy (CRT) with capecitabine and weekly irinotecan followed by laparoscopic total mesorectal excision (LTME) in rectal cancer patients.

    abstract:BACKGROUND:To analyze the feasibility of capecitabine with weekly irinotecan and concurrent radiotherapy followed by laparoscopic-total mesorectal excision (LTME) in rectal cancer patients. METHODS:Eligible criteria included adenocarcinoma of the rectum staged by endoscopic ultrasonography (u), spiral abdominal and pe...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Ugidos L,Delgado S,Conill C,Ginés A,Gallego R,Ayuso JR,Miquel R,Tosca M,de Lacy A,Castells A,Maurel J

    更新日期:2009-06-01 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


    authors: Prentice HG,Wimperis JZ,Robbins G

    更新日期:1985-01-01 00:00:00

  • Plasma and cerebrospinal fluid pharmacokinetics of vincristine and vincristine sulfate liposomes injection (VSLI, marqibo®) after intravenous administration in Non-human primates.

    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


    authors: Shah NN,Cole DE,Lester-McCully CM,Wayne AS,Warren KE,Widemann BC

    更新日期:2016-02-01 00:00:00

  • A phase I trial of PTK787/ZK222584 in combination with pemetrexed and cisplatin in patients with advanced solid tumors.

    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


    authors: Sharma S,Freeman B,Turner J,Symanowski J,Manno P,Berg W,Vogelzang N

    更新日期:2009-02-01 00:00:00

  • Effect of alisertib, an investigational aurora a kinase inhibitor on the QTc interval in patients with advanced malignancies.

    abstract::Aims A primary objective of this study was to investigate the effect of single and multiple doses of alisertib, an investigational Aurora A kinase inhibitor, on the QTc interval in patients with advanced malignancies. The dose regimen used was the maximum tolerated dose which was also the recommended phase 3 dose (50 ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Zhou X,Nemunaitis J,Pant S,Bauer TM,Patel M,Sarantopoulos J,Craig Lockhart A,Goodman D,Huebner D,Mould DR,Venkatakrishnan K

    更新日期:2018-04-01 00:00:00

  • Phase II trial of ifosfamide in epidermoid carcinoma of the esophagus: unexpectant severe toxicity.

    abstract::Thirty-two patients with advanced epidermoid carcinoma of the esophagus were treated with ifosfamide (1.50 gm/m2 daily x 5 days) with uroprotective mesna in a phase II study. Eighteen patients were previously untreated. Of 28 evaluable patients, two (7%) had partial remissions lasting 2+ and 6+ months. Toxicity was pr...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Nanus DM,Kelsen DP,Lipperman R,Eisenberger M

    更新日期:1988-09-01 00:00:00

  • Phase Ia/Ib study of the pan-class I PI3K inhibitor pictilisib (GDC-0941) administered as a single agent in Japanese patients with solid tumors and in combination in Japanese patients with non-squamous non-small cell lung cancer.

    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


    authors: Yamamoto N,Fujiwara Y,Tamura K,Kondo S,Iwasa S,Tanabe Y,Horiike A,Yanagitani N,Kitazono S,Inatani M,Tanaka J,Nishio M

    更新日期:2017-02-01 00:00:00

  • Phase 1b investigation of the MEK inhibitor binimetinib in patients with advanced or metastatic biliary tract cancer.

    abstract::Background The MAPK pathway plays a central role in regulation of several cellular processes, and its dysregulation is a hallmark of biliary tract cancer (BTC). Binimetinib (MEK162), a potent, selective oral MEK1/2 inhibitor, was assessed in patients with advanced BTC. Patients and Methods An expansion cohort study in...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究


    authors: Finn RS,Ahn DH,Javle MM,Tan BR Jr,Weekes CD,Bendell JC,Patnaik A,Khan GN,Laheru D,Chavira R,Christy-Bittel J,Barrett E,Sawyer MB,Bekaii-Saab TS

    更新日期:2018-12-01 00:00:00

  • Pharmacokinetics of 5,6-dihydro-5-azacytidine (NSC-264880) in the foxhound.

    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


    authors: Malspeis L,Cheng H,Staubus AE

    更新日期:1983-01-01 00:00:00

  • Cytotoxic flavonoids and isoflavonoids from Erythrina sigmoidea towards multi-factorial drug resistant cancer cells.

    abstract:INTRODUCTION:Continuous efforts from scientists of diverse fields are necessary not only to better understand the mechanism by which multidrug resistant (MDR) cancer cells occur, but also to boost the discovery of new cytotoxic compounds. This work was designed to assess the cytotoxicity and the mechanism of action of ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Kuete V,Sandjo LP,Djeussi DE,Zeino M,Kwamou GM,Ngadjui B,Efferth T

    更新日期:2014-12-01 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


    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

  • Synergistic combination of menogarol and melphalan and other two drug combinations.

    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


    authors: Bhuyan BK,Adams EG,Johnson M,Crampton SL

    更新日期:1985-01-01 00:00:00

  • Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors.

    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


    authors: Galsky MD,Von Hoff DD,Neubauer M,Anderson T,Fleming M,Nagarwala Y,Mahoney JM,Midwinter D,Vocila L,Zaks TZ

    更新日期:2012-04-01 00:00:00

  • Luteolin inhibits cell proliferation during Azoxymethane-induced experimental colon carcinogenesis via Wnt/ β-catenin pathway.

    abstract::The protective role of Luteolin (LUT) against Azoxymethane (AOM)-induced mouse colon carcinogenesis has been documented earlier. The aim of this study is to investigate on the mechanism of chemopreventive action exhibited by LUT employing AOM-induced colon carcinogenesis in mice as an experimental model. LUT inhibited...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Ashokkumar P,Sudhandiran G

    更新日期:2011-04-01 00:00:00

  • 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


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

    更新日期:2010-12-01 00:00:00

  • SHetA2 interference with mortalin binding to p66shc and p53 identified using drug-conjugated magnetic microspheres.

    abstract::SHetA2 is a small molecule flexible heteroarotinoid (Flex-Het) with promising cancer prevention and therapeutic activity. Extensive preclinical testing documented lack of SHetA2 toxicity at doses 25 to 150 fold above effective doses. Knowledge of the SHetA2 molecular target(s) that mediate(s) the mechanism of SHetA2 a...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Benbrook DM,Nammalwar B,Long A,Matsumoto H,Singh A,Bunce RA,Berlin KD

    更新日期:2014-06-01 00:00:00

  • Phase I study of matuzumab in combination with 5-fluorouracil, leucovorin and cisplatin (PLF) in patients with advanced gastric and esophagogastric adenocarcinomas.

    abstract:BACKGROUND:To evaluate the safety and tolerability of two different weekly doses of the fully humanized epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab combined with high-dose 5-fluorouracil, leucovorin and cisplatin (PLF) in the first-line treatment of patients with EGFR-positive advanc...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Trarbach T,Przyborek M,Schleucher N,Heeger S,Lüpfert C,Vanhoefer U

    更新日期:2013-06-01 00:00:00

  • Studies on the cytotoxic, biochemical and anti-carcinogenic potentials of ninhydrin on Ehrlich ascites carcinoma cell-bearing Swiss albino mice.

    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


    authors: Qureshi S,Al-Shabanah OA,Al-Bekairi AM,Al-Harbi MM,Al-Gharably NM,Raza M

    更新日期:2000-08-01 00:00:00