INNO-206, the (6-maleimidocaproyl hydrazone derivative of doxorubicin), shows superior antitumor efficacy compared to doxorubicin in different tumor xenograft models and in an orthotopic pancreas carcinoma model.


:The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (INNO-206) is an albumin-binding prodrug of doxorubicin with acid-sensitive properties that is being assessed clinically. The prodrug binds rapidly to circulating serum albumin and releases doxorubicin selectively at the tumor site. This novel mechanism may provide enhanced antitumor activity of doxorubicin while improving the overall toxicity profile. Preclinically, INNO-206 has shown superior activity over doxorubicin in a murine renal cell carcinoma model and in breast carcinoma xenograft models. In this work, we compared the antitumor activity of INNO-206 and doxorubicin at their respective maximum tolerated doses in three additional xenograft models (breast carcinoma 3366, ovarian carcinoma A2780, and small cell lung cancer H209) as well as in an orthotopic pancreas carcinoma model (AsPC-1). INNO-206 showed more potent antitumor efficacy than free doxorubicin in all tumor models and is thus a promising clinical candidate for treating a broad range of solid tumors.


Invest New Drugs


Graeser R,Esser N,Unger H,Fichtner I,Zhu A,Unger C,Kratz F




Has Abstract


2010-02-01 00:00:00












  • Phase II trial of intravenous melphalan for metastatic colorectal carcinoma. A Southwest Oncology Group study.

    abstract::Based on the high response rates seen among patients with colon cancer receiving high dose Melphalan with autologous marrow infusion, the Southwest Oncology Group conducted a Phase II trial of the compound at a conventional dose. The initial starting dose of 40 mg/m2 was reduced to 30 mg/m2 after severe myelotoxicity ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Knight WA 3rd,Goodman P,Taylor SA,Macdonald JS,Coltman CA Jr,Constanzi JJ,Baker LH

    更新日期:1990-01-01 00:00:00

  • Growth inhibition induced by antiprogestins RU-38486, ORG-31710, and CDB-2914 in ovarian cancer cells involves inhibition of cyclin dependent kinase 2.

    abstract::Antiprogestins have been largely utilized in reproductive medicine, yet their repositioning for oncologic use is rapidly emerging. In this study we investigated the molecular mediators of the anti-ovarian cancer activity of the structurally related antiprogestins RU-38486, ORG-31710 and CDB-2914. We studied the respon...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Goyeneche AA,Seidel EE,Telleria CM

    更新日期:2012-06-01 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


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

    更新日期:2011-04-01 00:00:00

  • Assessment of the cytotoxic effects of aporphine prototypes on head and neck cancer cells.

    abstract::Purpose Among alkaloids, abundant secondary metabolites in plants, aporphines constitute a class of compounds with interesting biological activities, including anticancer effects. The present study evaluated the anticancer activities of 14 substances, including four aporphine derivatives acquired through the biomonito...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Rodrigues-Junior DM,de Almeida Pontes NM,de Albuquerque GE,Carlin V,Perecim GP,Raminelli C,Vettore AL

    更新日期:2020-02-01 00:00:00

  • Phase I study of metformin in combination with carboplatin/paclitaxel chemotherapy in patients with advanced epithelial ovarian cancer.

    abstract::Background Metformin use is associated with reduced cancer risk in epidemiological studies and has preclinical anti-cancer activity in ovarian cancer models. The primary objective of this phase I study was to determine the recommended phase II dose (RP2D) of metformin in combination with carboplatin/paclitaxel in pati...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Broekman KE,Hof MAJ,Touw DJ,Gietema JA,Nijman HW,Lefrandt JD,Reyners AKL,Jalving M

    更新日期:2020-10-01 00:00:00

  • A randomized, open-label, multicenter, phase II study evaluating the efficacy and safety of BTH1677 (1,3-1,6 beta glucan; Imprime PGG) in combination with cetuximab and chemotherapy in patients with advanced non-small cell lung cancer.

    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


    authors: Thomas M,Sadjadian P,Kollmeier J,Lowe J,Mattson P,Trout JR,Gargano M,Patchen ML,Walsh R,Beliveau M,Marier JF,Bose N,Gorden K,Schneller F 3rd

    更新日期:2017-06-01 00:00:00

  • Phase 1 study of the oral histone deacetylase inhibitor abexinostat in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, or chronic lymphocytic leukaemia.

    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


    authors: Morschhauser F,Terriou L,Coiffier B,Bachy E,Varga A,Kloos I,Lelièvre H,Sarry AL,Depil S,Ribrag V

    更新日期:2015-04-01 00:00:00

  • Level of HER2/neu gene amplification as a predictive factor of response to trastuzumab-based therapy in patients with HER2-positive metastatic breast cancer.

    abstract::To explore the clinical significance of the level of HER2/neu gene amplification in a homogenous cohort of 33 patients with HER2-positive metastatic breast cancer (MBC) and available tumor samples treated with a trastuzumab-based regimen, we retrospectively performed dual-color fluorescence in-situ hybridization test ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Gullo G,Bettio D,Torri V,Masci G,Salvini P,Santoro A

    更新日期:2009-04-01 00:00:00

  • Capecitabine: preclinical pharmacology studies.

    abstract::Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a novel fluoropyrimidine carbamate, which was designed to be sequentially converted to 5-fluorouracil (5-FU) by three enzymes located in the liver and in tumors; the final step is the conversion of 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-FU by thymidine ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审


    authors: Ishitsuka H

    更新日期:2000-11-01 00:00:00

  • Down-regulation of P-cadherin with PF-03732010 inhibits cell migration and tumor growth in gastric cancer.

    abstract::P-cadherin is frequently up-regulated in solid tumors such as gastric, colon, lung, pancreatic and breast cancers. Although P-cadherin promotes cadherin-mediated cell adhesion, the gastric cancer-linked regulation of P-cadherin has not been extensively investigated. In this study, we found epigenetic regulation of P-c...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Park J,Park E,Han SW,Im SA,Kim TY,Kim WH,Oh DY,Bang YJ

    更新日期:2012-08-01 00:00:00

  • Risk factors for cancer-associated thrombosis in patients undergoing treatment with immune checkpoint inhibitors.

    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


    authors: Ando Y,Hayashi T,Sugimoto R,Nishibe S,Ito K,Kawada K,Ikeda Y,Yamada S,Imaizumi K

    更新日期:2020-08-01 00:00:00

  • Phase 1/2 study of orteronel (TAK-700), an investigational 17,20-lyase inhibitor, with docetaxel-prednisone in metastatic castration-resistant prostate cancer.

    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


    authors: Petrylak DP,Gandhi JG,Clark WR,Heath E,Lin J,Oh WK,Agus DB,Carthon B,Moran S,Kong N,Suri A,Bargfrede M,Liu G

    更新日期:2015-04-01 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 II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced hepatocellular carcinoma.

    abstract:UNLABELLED:Although UFT 300 mg/m2/day and leucovorin 90 mg/day administered orally in divided doses administered every 8 hours for 28 days repeated every 35 days could be administered safely to patients with advanced hepatomas and good performance status, this combination and schedule has limited activity in treating a...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章


    authors: Mani S,Schiano T,Garcia JC,Ansari RH,Samuels B,Sciortino DF,Tembe S,Shulman KL,Baker A,Benner SE,Vokes EE

    更新日期:1998-01-01 00:00:00

  • Is transketolase like 1 a target for the treatment of differentiated thyroid carcinoma? A study on thyroid cancer cell lines.

    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


    authors: Fröhlich E,Fink I,Wahl R

    更新日期:2009-08-01 00:00:00

  • Distribution, elimination, metabolism and bioavailability of hexamethylenebisacetamide in rats.

    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


    authors: Litterst CL,Roth JS,Kelley JA

    更新日期:1985-01-01 00:00:00

  • Population pharmacokinetic analysis of AR-67, a lactone stable camptothecin analogue, in cancer patients with solid tumors.

    abstract::Background AR-67 is a novel camptothecin analogue at early stages of drug development. The phase 1 clinical trial in cancer patients with solid tumors was completed and a population pharmacokinetic model (POP PK) was developed to facilitate further development of this investigational agent. Methods Pharmacokinetic dat...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Tang F,Tsakalozou E,Arnold SM,Ng CM,Leggas M

    更新日期:2019-12-01 00:00:00

  • Phase II trial of single-agent foretinib (GSK1363089) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

    abstract:BACKGROUND:Foretinib is a small-molecule, oral multikinase inhibitor primarily targeting the mesenchymal epithelial transition (MET) factor receptor, and the vascular endothelial growth factor receptor 2. We conducted a phase II study to evaluate the single-agent activity and tolerability of foretinib in patients with ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究


    authors: Seiwert T,Sarantopoulos J,Kallender H,McCallum S,Keer HN,Blumenschein G Jr

    更新日期:2013-04-01 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 study of oral CP-4126, a gemcitabine derivative, in patients with advanced solid tumors.

    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


    authors: Stuurman FE,Voest EE,Awada A,Witteveen PO,Bergeland T,Hals PA,Rasch W,Schellens JH,Hendlisz A

    更新日期:2013-08-01 00:00:00

  • Phase II trial of menogaril in metastatic adenocarcinoma of the prostate. A Southwest Oncology Group study.

    abstract::Menogaril, a semisynthetic anthracycline antibiotic, was administered to patients with metastatic adenocarcinoma of the prostate. Forty-five patients with measurable disease and 45 patients with evaluable disease received 150-200 mg/m2 over 1 hour every 28 days. There were three partial responses (PR) among 87 patient...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Taylor SA,Blumenstein BA,Stephens RL,Crawford ED,Pistone B,Hill JB

    更新日期:1994-01-01 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

  • Phase II trial of topotecan in advanced gastric cancer: a Southwest Oncology Group study.

    abstract::Topotecan (NSC 609099) is a camptothecin analogue that demonstrated activity against a variety of human tumors in preclinical studies. A phase II trial was performed with topotecan given to patients with locally advanced or metastatic adenocarcinoma of the stomach. Topotecan was administered IV Bolus over 30 minutes o...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章


    authors: Benedetti JK,Burris HA 3rd,Balcerzak SP,Macdonald JS

    更新日期:1997-01-01 00:00:00

  • N-Methylformamide in advanced squamous cancer of the uterine cervix: an Eastern Cooperative Oncology Group phase II trial.

    abstract:PURPOSE:Preclinical and clinical data support the study of polar-planar compounds such as N-Methylformamide (NMF) in advanced squamous cell carcinoma of the uterine cervix (SCC). This phase II trial sought to determine the efficacy and toxicities of NMF in patients with advanced SCC. PATIENTS AND METHODS:Eligibility f...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Rajdev L,Yu ZF,Wadler S,Weller E,Kahn SB,Tormey D,Skeel R,Wiernik PH

    更新日期:2001-01-01 00:00:00

  • Proteasome inhibition and mechanism of resistance to a synthetic, library-based hexapeptide.

    abstract::Background The hexapeptide 4A6 (Ac-Thr(tBu)-His(Bzl)-Thr(Bzl)-Nle-Glu(OtBu)-Gly-Bza) was isolated from a peptide library constructed to identify peptide-based transport inhibitors of multidrug resistance (MDR) efflux pumps including P-glycoprotein and Multidrug Resistance-associated Protein 1. 4A6 proved to be a subst...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Oerlemans R,Berkers CR,Assaraf YG,Scheffer GL,Peters GJ,Verbrugge SE,Cloos J,Slootstra J,Meloen RH,Shoemaker RH,Dijkmans BAC,Scheper RJ,Ovaa H,Jansen G

    更新日期:2018-10-01 00:00:00

  • The in vitro assessment of dipyridophenazine complexes in H-ras oncogene transformed rat embryo fibroblast 5RP7 cell line.

    abstract::Purpose The aim of this study is to detect apoptotic and cytotoxic/antiproliferative effects of a ligand substance and its metal derivatives. The substances were investigated by using an h-ras oncogene transformed rat embryo fibroblast cell line (5RP7). Methods The cytotoxic influences of dipyrido[3,2-a:2',3'c]phenazi...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Kaplan A,Benkli K,Koparal AT

    更新日期:2018-10-01 00:00:00

  • Chemosensitivity of various peritoneal cancer cell lines to HIPEC and PIPAC: comparison of an experimental duplex drug to standard drug regimens in vitro.

    abstract::We performed an in-vitro study testing the chemosensitivity of peritoneal cancer cell lines (SW620, HCT116, MKN45, 23,132/87, OAW42) to various cytostatic drug regimens. A duplex drug, characterized by reversible linking of the antimetabolites 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), was compa...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Weinreich J,Struller F,Sautkin I,Giuashvili S,Reymond M,Königsrainer A,Schott TC

    更新日期:2019-06-01 00:00:00

  • A phase I safety and pharmacokinetic study of ABT-263 in combination with carboplatin/paclitaxel in the treatment of patients with solid tumors.

    abstract::Bcl-2 family proteins are the key regulators of the intrinsic apoptotic pathway, controlling the point-of no-return and setting the threshold to engage the death machinery in response to chemical damage. Bcl-2 proteins have emerged as attractive targets for anti-cancer drug development. Navitoclax is a selective, pote...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Vlahovic G,Karantza V,Wang D,Cosgrove D,Rudersdorf N,Yang J,Xiong H,Busman T,Mabry M

    更新日期:2014-10-01 00:00:00

  • TRAIL shows potential cardioprotective activity.

    abstract::Recent clinical trials carried out in patients with advanced cancer have shown that recombinant TRAIL administration is usually safe and well tolerated when used either alone or in association with chemotherapeutic drugs. Notably, anticancer chemotherapy can be associated to cardiomiopathy. We have here demonstrated t...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Toffoli B,Bernardi S,Candido R,Zacchigna S,Fabris B,Secchiero P

    更新日期:2012-06-01 00:00:00

  • Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways.

    abstract::Withaferin A (WA), a steroidal lactone derived from the plant Vassobia breviflora, has been reported to have anti-proliferative, pro-apoptotic, and anti-angiogenic properties against cancer growth. In this study, we identified several key underlying mechanisms of anticancer action of WA in glioblastoma cells. WA was f...

    journal_title:Investigational new drugs

    pub_type: 杂志文章


    authors: Grogan PT,Sleder KD,Samadi AK,Zhang H,Timmermann BN,Cohen MS

    更新日期:2013-06-01 00:00:00