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












  • Mitoxantrone in the treatment of relapsed and refractory acute leukemia.

    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


    authors: Meyer P,Ho AD,Ehninger G,Mjaaland I,Heidemann E,Seither E

    更新日期:1985-01-01 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

  • Contributions from emerging transcriptomics technologies and computational strategies for drug discovery.

    abstract::Drug discovery involves various steps and is a long process being even more demanding for complex diseases such as cancer. Tumors are ensembles of subpopulations with different mutations, require very specific and effective strategies. Conventional drug screening technologies may not be adequate and efficient anymore....

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审


    authors: Kadioglu O,Efferth T

    更新日期:2014-12-01 00:00:00

  • A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer.

    abstract:BACKGROUND:We evaluated the efficacy and safety of cetuximab in combination with XELOX [XELoda® (capecitabine) and OXaliplatin] in advanced gastric cancer (AGC) patients. The objectives were to evaluate overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety of cetuximab plus XEL...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究


    authors: Kim C,Lee JL,Ryu MH,Chang HM,Kim TW,Lim HY,Kang HJ,Park YS,Ryoo BY,Kang YK

    更新日期:2011-04-01 00:00:00

  • Erlotinib pharmacokinetics: a critical parameter influencing acute toxicity in elderly patients over 75 years-old.

    abstract::Background Older non-small cell lung cancer (NSCLC) patients under erlotinib are reported to experience more acute toxicity. We hypothesized that modifications in erlotinib pharmacokinetics might explain this observation. Methods A monocentric prospective clinico-pharmacological study included stage IIIb/IV NSCLC cons...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章


    authors: Bigot F,Boudou-Rouquette P,Arrondeau J,Thomas-Schoemann A,Tlemsani C,Chapron J,Huillard O,Cessot A,Vidal M,Alexandre J,Blanchet B,Goldwasser F

    更新日期:2017-04-01 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

  • A multicenter, phase II study of bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma.

    abstract:PURPOSE:The transcription factor nuclear factor-kB (NFkB) is implicated in gastric cancer carcinogenesis and survival, and its inhibition by proteosome inhibition is associated with preclinical gastric cancer anti-tumor activity. We examined the single agent efficacy of bortezomib, a selective proteasome inhibitor, in ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究


    authors: Shah MA,Power DG,Kindler HL,Holen KD,Kemeny MM,Ilson DH,Tang L,Capanu M,Wright JJ,Kelsen DP

    更新日期:2011-12-01 00:00:00

  • Clinical pharmacokinetic/pharmacodynamic and physiologically based pharmacokinetic modeling in new drug development: the capecitabine experience.

    abstract::Preclinical studies, along with Phase I, II, and III clinical trials demonstrate the pharmacokinetics, pharmacodynamics, safety and efficacy of a new drug under well controlled circumstances in relatively homogeneous populations. However, these types of studies generally do not answer important questions about variabi...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审


    authors: Blesch KS,Gieschke R,Tsukamoto Y,Reigner BG,Burger HU,Steimer JL

    更新日期:2003-05-01 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

  • Synergistic effects of the combination of β-ionone and sorafenib on metastasis of human hepatoma SK-Hep-1 cells.

    abstract::The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy of chemotherapy, particularly for hepatocellular carcinoma because its conventional therapies are mostly ineffective. Using a highly invasive hepatoma SK-Hep-1 cell line, we investigated the possible synerg...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Huang CS,Lyu SC,Hu ML

    更新日期:2012-08-01 00:00:00

  • Structure-activity relationships between the Aconitum C20-diterpenoid alkaloid derivatives and the growth suppressive activities of Non-Hodgkin's lymphoma Raji cells and human hematopoietic stem/progenitor cells.

    abstract::The anti-tumor properties of novel derivatives prepared from Aconitum C(20)-diterpenoid alkaloid, which show the least toxicity among the Aconitum alkaloids, were investigated in the Non-Hodgkin's lymphoma cell line Raji cells. Two novel Aconitum C(20)-diterpenoid alkaloid derivatives, 11-m-Trifluorometylbenzoyl (Mb)-...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Hazawa M,Takahashi K,Wada K,Mori T,Kawahara N,Kashiwakura I

    更新日期:2011-02-01 00:00:00

  • Phase I, dose-escalating study of elisidepsin (Irvalec(®)), a plasma membrane-disrupting marine antitumor agent, in combination with erlotinib in patients with advanced malignant solid tumors.

    abstract:OBJECTIVE:To determine the recommended dose for phase II trials of elisidepsin (PM02734, Irvalec®) in combination with erlotinib in patients with advanced malignant solid tumors. METHODS:Open-label, dose-escalating, phase I study of intravenous elisidepsin administered weekly (days 1, 8 and 15) over 3 h as a flat dose...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究


    authors: Goel S,Viteri S,Morán T,Coronado C,Dios JL,Miguel-Lillo B,Fernández-García EM,Rosell R

    更新日期:2016-02-01 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

  • Phase II study of selumetinib, an orally active inhibitor of MEK1 and MEK2 kinases, in KRASG12R-mutant pancreatic ductal adenocarcinoma.

    abstract::Background Preclinical evidence has suggested that a subset of pancreatic cancers with the G12R mutational isoform of the KRAS oncogene is more sensitive to MAPK pathway blockade than pancreatic tumors with other KRAS isoforms. We conducted a biomarker-driven trial of selumetinib (KOSELUGO™; ARRY-142886), an orally ac...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Kenney C,Kunst T,Webb S,Christina D Jr,Arrowood C,Steinberg SM,Mettu NB,Kim EJ,Rudloff U

    更新日期:2021-01-06 00:00:00

  • A phase I trial of the bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC3095 in patients with advanced solid malignancies.

    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


    authors: Schwartsmann G,DiLeone LP,Horowitz M,Schunemann D,Cancella A,Pereira AS,Richter M,Souza F,da Rocha AB,Souza FH,Pohlmann P,De Nucci G

    更新日期:2006-09-01 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

  • Phase II trial of 4' deoxydoxorubicin (DXDX) for unresectable non-small cell bronchogenic carcinoma. An Illinois Cancer Council study.

    abstract::A phase II trial of 4' Deoxydoxorubicin (DXDX) was conducted in unresectable previously untreated non-small cell lung cancer patients. DXDX was administered every 3 weeks by short intravenous infusion at a starting dose of 30 mg/m2, with dose escalation to 40 mg/m2 toxicity permitting. Four responses, all partial, wer...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Rose C,Lad TE,Kilton LJ,Schor J,Rosen ST,Rossof AH,Blough RR,Johnson CM

    更新日期:1990-02-01 00:00:00

  • Phase II feasibility study of high dose epirubicin plus etoposide and cisplatin (HDEEC) regimen in small cell lung cancer.

    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


    authors: Rosell R,Carles J,Abad A,Jimeno JM,Moreno I,Barnadas A,Ribelles N,Haboubi N

    更新日期:1992-07-01 00:00:00

  • A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family inhibitor, in combination with gemcitabine in patients with solid tumors.

    abstract:PURPOSE:To investigate the safety, optimal dosing, pharmacokinetics and clinical activity of a regimen of navitoclax (ABT-263) combined with gemcitabine in patients with solid tumors. EXPERIMENTAL DESIGN:Patients with solid tumors for which gemcitabine was deemed an appropriate therapy were enrolled into one of two di...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Cleary JM,Lima CM,Hurwitz HI,Montero AJ,Franklin C,Yang J,Graham A,Busman T,Mabry M,Holen K,Shapiro GI,Uronis H

    更新日期:2014-10-01 00:00:00

  • Therapeutic efficacy and imaging assessment of the HER2-targeting chemotherapy drug ZHER2:V2-pemetrexed in lung adenocarcinoma Xenografts.

    abstract::Chemotherapy has always been the first therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) with untreatable oncogenic mutations. However, chemotherapy has demonstrated limited success and is associated with severe side effects. This research aimed to investigate the antitumor efficacy and ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Han J,Zhao Y,Zhao X,Ma T,Hao T,Liu J,Zhang Z,Zhang J,Wang J

    更新日期:2020-08-01 00:00:00

  • Inhibitory activity of diarylamidine derivatives on murine leukemia L1210 cell growth.

    abstract::A series of 96 diarylamidine (and diarylimidazoline) derivatives were evaluated for their inhibitory effects on the growth and DNA synthesis of murine leukemia L1210 cells. The amidino- and imidazolino-substituted aryl moieties of the compounds consisted of phenyl, indole, indene, benzofuran, benzo[b]thiophene or benz...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Balzarini J,de Clercq E,Dann O

    更新日期:1983-01-01 00:00:00

  • Preclinical efficacy evaluations of XK-469: dose schedule, route and cross-resistance behavior in tumor bearing mice.

    abstract::XK-469 is advancing to Phase I clinical trials. Preclinical studies were carried out to assist in clinical applications. DOSE-SCHEDULE ROUTE TESTING: Single dose i.v. treatment with XK-469 produced lethality (LD20 to LD100) above 142 mg/kg. Optimum treatment required total dosages of 350 to 600 mg/kg. Furthermore, hig...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Polin L,White K,Kushner J,Paluch J,Simpson C,Pugh S,Edelstein MK,Hazeldine S,Fontana J,LoRusso P,Horwitz JP,Corbett TH

    更新日期:2002-02-01 00:00:00

  • A new diaryl urea compound, D181, induces cell cycle arrest in the G1 and M phases by targeting receptor tyrosine kinases and the microtubule skeleton.

    abstract::Receptor tyrosine kinases (RTKs) modulate a variety of cellular events, including cell proliferation, differentiation, mobility and apoptosis. In addition, RTKs have been validated as targets for cancer therapies. Microtubules are another class of proven targets for many clinical anticancer drugs. Here, we report that...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Zhang J,Zhou J,Ren X,Diao Y,Li H,Jiang H,Ding K,Pei D

    更新日期:2012-04-01 00:00:00

  • Phase I and pharmacokinetic study of dacomitinib (PF-00299804), an oral irreversible, small molecule inhibitor of human epidermal growth factor receptor-1, -2, and -4 tyrosine kinases, in Japanese patients with advanced solid tumors.

    abstract:BACKGROUND:Dacomitinib (PF-00299804) is an oral, irreversible, small molecule inhibitor of human epidermal growth factor receptor-1, -2, and -4 tyrosine kinases. METHODS:This phase I, open-label, dose-escalation study (clinicaltrials.gov: NCT00783328) primarily evaluated the safety and tolerability of dacomitinib by d...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Takahashi T,Boku N,Murakami H,Naito T,Tsuya A,Nakamura Y,Ono A,Machida N,Yamazaki K,Watanabe J,Ruiz-Garcia A,Imai K,Ohki E,Yamamoto N

    更新日期:2012-12-01 00:00:00

  • Atezolizumab plus carboplatin and etoposide in small cell lung cancer patients previously treated with platinum-based chemotherapy.

    abstract::Although immune checkpoint inhibitors have improved the survival of small cell lung cancer (SCLC) patients, their efficacy in SCLC patients who relapsed after systemic chemotherapy is unclear. This retrospective study aimed to investigate the utility of treatment with atezolizumab plus carboplatin and etoposide in SCL...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Ishii H,Azuma K,Kawahara A,Matsuo N,Tokito T,Hoshino T

    更新日期:2020-08-11 00:00:00

  • Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib.

    abstract::Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib tre...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Yamamoto Y,Okamoto I,Otsubo K,Iwama E,Hamada N,Harada T,Takayama K,Nakanishi Y

    更新日期:2015-10-01 00:00:00

  • Developmental antiangiogenic agents for the treatment of non-small cell lung cancer (NSCLC).

    abstract::Standard therapy for advanced or metastatic non-small cell lung cancer (NSCLC) has primarily consisted of traditional cytotoxic chemotherapy, although use of targeted therapies has been approved in specific settings. Antiangiogenic agents represent a promising therapeutic strategy for treatment of advanced NSCLC. Beva...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审


    authors: Blumenschein GR Jr

    更新日期:2012-08-01 00:00:00

  • Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours.

    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


    authors: Devriese LA,Koch KM,Mergui-Roelvink M,Matthys GM,Ma WW,Robidoux A,Stephenson JJ,Chu QS,Orford KW,Cartee L,Botbyl J,Arya N,Schellens JH

    更新日期:2014-06-01 00:00:00

  • A phase II study of farnesyl transferase inhibitor R115777 in pancreatic cancer: a Southwest oncology group (SWOG 9924) study.

    abstract::Ninety per cent of pancreatic adenocarcinomas (PC) contain mutations of the K-Ras proto-oncogene resulting in constitutively activated Ras protein. A critical step in Ras activation is farnesylation of Ras protein. Farnesyl transferase inhibitors are compounds that inhibit farnesylation. We report the results of a pha...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Macdonald JS,McCoy S,Whitehead RP,Iqbal S,Wade JL 3rd,Giguere JK,Abbruzzese JL

    更新日期:2005-10-01 00:00:00

  • Targeting histone deacetyalses in the treatment of B- and T-cell malignancies.

    abstract::HDAC inhibitors (HDACI) are now emerging as one of the most promising new classes of drugs for the treatment of select forms of non-Hodgkin's lymphoma (NHL). They are particularly active in T-cell lymphomas, possibly hodgkin's lymphoma and indolent B cell lymphomas. Presently, two of these agents, vorinostat and romid...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Zain J,O'Connor OA

    更新日期:2010-12-01 00:00:00