Predictors for establishing recommended phase 2 doses: analysis of 320 dose-seeking oncology phase 1 trials.

abstract：:Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic melanoma and other cancers and have shown promising results. Inhibition of CTLA-4 characteristically induces well-known side effects called "immune-related adverse ...

journal_title：Investigational new drugs

authors： Izzedine H,Gueutin V,Gharbi C,Mateus C,Robert C,Routier E,Thomas M,Baumelou A,Rouvier P

更新日期：2014-08-01 00:00:00

abstract：:We have previously shown that the insulinotropic imidazoline compound RX871024 induces death of insulinoma MIN6 cells, an effect involving stimulation of c-Jun N-terminal kinase (JNK) and caspase 3. It has also been reported that AMP-activated protein kinase (AMPK) activates JNK and induces β-cell death. Here we show ...

journal_title：Investigational new drugs

authors： Zaitseva II,Zaitsev SV,Berggren PO

更新日期：2016-08-01 00:00:00

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

authors： Kadioglu O,Efferth T

更新日期：2014-12-01 00:00:00

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

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

abstract：:This report shows that N-acylation of the protein kinase C (PKC) substrate Arg-Lys-Arg-Thr-Leu-Arg-Arg-Leu (RKRTLRRL) provides it with a potent inhibitory activity against PKC. N-myristoyl-RKRTLRRL inhibited Ca2(+)- and phosphatidylserine (PS)-dependent histone phosphorylation catalyzed by PKC with a 50% inhibitory co...

journal_title：Investigational new drugs

authors： O'Brian CA,Ward NE,Liskamp RM,de Bont DB,Earnest LE,van Boom JH,Fan D

更新日期：1991-05-01 00:00:00

abstract：:This study aimed to analyze the oncology "drug lag" (i.e., the delay in time required for the approval of oncology drugs) in Japan compared with that in the United States of America (US) or the European Union (EU) and to identify the factors associated with this lag. Using publicly available information, we collected ...

journal_title：Investigational new drugs

authors： Yonemori K,Hirakawa A,Ando M,Hirata T,Yunokawa M,Shimizu C,Katsumata N,Tamura K,Fujiwara Y

更新日期：2011-08-01 00:00:00

abstract：BACKGROUND:This phase I, dose-finding study evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of sunitinib plus S-1/cisplatin in Japanese patients with advanced/metastatic gastric cancer. PATIENTS AND METHODS:Patients received oral sunitinib on a continuous daily dosing (CDD)...

journal_title：Investigational new drugs

authors： Boku N,Muro K,Machida N,Hashigaki S,Kimura N,Suzuki M,Lechuga M,Miyata Y

更新日期：2014-04-01 00:00:00

abstract：:Cribrostatin 6 is a quinone-containing natural product that induces the death of cancer cell lines in culture, and its mechanism of action and scope of activity are unknown. Here we show that cribrostatin 6 has broad anticancer activity, potently inducing apoptotic cell death that is not preceded by any defined cell c...

journal_title：Investigational new drugs

authors： Hoyt MT,Palchaudhuri R,Hergenrother PJ

更新日期：2011-08-01 00:00:00

abstract：:Background This first-in-human phase 1 study assessed the safety of TAS-114, a novel deoxyuridine triphosphatase inhibitor, combined with S-1 to determine its maximum tolerated dose (MTD) and recommended dose (RD). Methods In this dose-escalation study with a 3 + 3 design, TAS-114 and S-1 were concurrently administere...

journal_title：Investigational new drugs

authors： Doi T,Yoh K,Shitara K,Takahashi H,Ueno M,Kobayashi S,Morimoto M,Okusaka T,Ueno H,Morizane C,Okano N,Nagashima F,Furuse J

更新日期：2019-06-01 00:00:00

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

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

abstract：:Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be required for tumor invasion, tumor-induced angiogenesis and vascular invasion. A synthetic hydroxamate, batimastat (also known as BB-94), inhibits MMPs by binding the zinc ion in the active site of the MMP. ...

journal_title：Investigational new drugs

authors： Wojtowicz-Praga S,Low J,Marshall J,Ness E,Dickson R,Barter J,Sale M,McCann P,Moore J,Cole A,Hawkins MJ

更新日期：1996-01-01 00:00:00

abstract：:Epidermal growth factor receptor (EGFR) gene mutations activate the KRAS-RAF-MEK-ERK pathway in lung cancer cells. EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib induce apoptosis of cancer cells, but prolonged treatment is often associated with acquired resistance. Here, we identified a novel MEK1/2 inhibito...

journal_title：Investigational new drugs

authors： Song JY,Kim CS,Lee JH,Jang SJ,Lee SW,Hwang JJ,Lim C,Lee G,Seo J,Cho SY,Choi J

更新日期：2013-12-01 00:00:00

abstract：:Idarubicin, a new analogue of daunorubicin, was administered to 27 patients with advanced breast cancer in a phase II trial. The drug was given orally at a dose of 30-35 mg/m2 every 3 weeks. Twenty-two patients were evaluable for response. All evaluable patients were previously treated with one or more chemotherapeuti...

journal_title：Investigational new drugs

authors： Lopez M,Di Lauro L,Papaldo P,Lazzaro B,Ganzina F,Di Pietro N

更新日期：1986-01-01 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

authors： Kim GP,Mahoney MR,Szydlo D,Mok TS,Marshke R,Holen K,Picus J,Boyer M,Pitot HC,Rubin J,Philip PA,Nowak A,Wright JJ,Erlichman C

更新日期：2012-02-01 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

authors： Infante JR,Benhadji KA,Dy GK,Fetterly G,Ma WW,Bendell J,Callies S,Adjei AA

更新日期：2015-04-01 00:00:00

abstract：:Apoptin is a nonstructural protein encoded by one of the three open reading frames of the chicken anemia virus genome. It has attracted a great deal of interest due to its ability to induce apoptosis in multiple transformed and malignant mammalian cell lines without affecting primary and non-transformed cells. However...

journal_title：Investigational new drugs

authors： Ruiz-Martínez S,Castro J,Vilanova M,Bruix M,Laurents DV,Ribó M,Benito A

更新日期：2017-06-01 00:00:00

abstract：:CC-1065 is a unique alkylating agent that preferentially binds in the minor groove of double-stranded DNA at adenine-thymine-rich sites. Although it has broad antitumor activity in preclinical models its development was discontinued because of deaths observed during preclinical toxicology studies. Adozelesin is a pote...

journal_title：Investigational new drugs

authors： Foster BJ,LoRusso PM,Poplin E,Zalupski M,Valdivieso M,Wozniak A,Flaherty L,Kasunic DA,Earhart RH,Baker LH

更新日期：1996-01-01 00:00:00

abstract：BACKGROUND:Gemcitabine (G) has shown activity in mantle cell lymphoma (MCL) as a single agent. The combination of mitoxantrone (M) and rituximab (R) is also active in MCL. The primary objective of this study was to determine the efficacy of G+M+R in relapsed or refractory MCL. PATIENTS AND METHODS:Sixteen patients wer...

journal_title：Investigational new drugs

authors： Garbo LE,Flynn PJ,MacRae MA,Rauch MA,Wang Y,Kolibaba KS

更新日期：2009-10-01 00:00:00

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

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

更新日期：1987-01-01 00:00:00

abstract：:Nafazatrom, a synthetic pyrazolinone derivative, has been shown to have substantial antitumor activity in vitro and antitumor and antimetastatic activity in experimental animal systems. The drug has produced no substantial toxicity in preclinical studies and during limited human trials. A phase I clinical trial with t...

journal_title：Investigational new drugs

authors： Hortobagyi GN,Papadoupoulos NE,Frye D,Ajani J,Reuben JM

更新日期：1986-01-01 00:00:00

abstract：:XK469 (NSC 656889) is a water-soluble member of the novel quinoxaline family of antitumor agents. In vitro, XK469 demonstrated selective cytotoxicity for several murine solid tumors including colorectal and mammary adenocarcinoma cell lines, when compared to both leukemia and normal epithelial cells. In vivo, XK469 wa...

journal_title：Investigational new drugs

authors： LoRusso PM,Parchment R,Demchik L,Knight J,Polin L,Dzubow J,Behrens C,Harrison B,Trainor G,Corbett TH

更新日期：1998-01-01 00:00:00

abstract：:We have previously described a human pancreatic-ribonuclease variant, named PE5, which carries a non-contiguous extended bipartite nuclear localization signal. This signal comprises residues from at least three regions of the protein. We postulated that the introduction of this signal in the ribonuclease provides it w...

journal_title：Investigational new drugs

authors： Tubert P,Rodríguez M,Ribó M,Benito A,Vilanova M

更新日期：2011-10-01 00:00:00

abstract：:Chloroquinoxaline sulfonamide (CQS) has been developed to the clinical trial stage based on its activity in the Human Tumor Colony Forming Assay (HTCFA). In the HTCFA, CQS demonstrated inhibition of colony formation against breast, lung, melanoma and ovarian carcinomas. The mechanism of action of CQS is unknown. It do...

journal_title：Investigational new drugs

authors： Fisherman JS,Osborn BL,Chun HG,Plowman J,Smith AC,Christian MC,Zaharko DS,Shoemaker RH

更新日期：1993-02-01 00:00:00

abstract：:Antiproliferative factor (APF) is a potent frizzled protein 8-related sialoglycopeptide inhibitor of bladder epithelial cell proliferation that mediates its activity by binding to cytoskeletal associated protein 4 in the cell membrane. Synthetic asialylated APF (as-APF) (Galβ1-3GalNAcα-O-TVPAAVVVA) was previously show...

journal_title：Investigational new drugs

authors： Koch KR,Zhang CO,Kaczmarek P,Barchi J Jr,Guo L,Shahjee HM,Keay S

更新日期：2012-10-01 00:00:00

abstract：:Infantile hemangioma is the most common vascular tumor of childhood. It is characterized by clinical expansion of endothelial cells and promoted by angiogenic factors. Luteolin is a flavonoid compound that carries anti-cancer and anti-angiogenesis properties. The study aimed to investigate the effect of luteolin in tr...

journal_title：Investigational new drugs

authors： Dai Y,Zheng H,Liu Z,Wang Y,Hu W

更新日期：2021-01-07 00:00:00

abstract：:Diflubenzuron (DFB) and Clanfenur (CFN) belong to a group of compounds called Benzoylphenyl Ureas (BPUs). Several BPUs regulate cell growth in insects and/or inhibit growth of B-16 murine melanomas. In view of potential clinical use for these compounds, DFB and CFN were selected as examples of BPUs and tested for effe...

journal_title：Investigational new drugs

authors： Jenkins VK,Juneja HS,Ives K,Lee S,Perry RR

更新日期：1993-11-01 00:00:00

abstract：BACKGROUND:We performed a phase I study to determine the dose and safety of everolimus as a combination chemotherapy in peripheral T-cell lymphoma (PTCL). METHODS:Four dose levels (2.5 to 10 mg) of everolimus from days 1 to 14 with CHOP (750 mg/m(2) cyclophosphamide, 50 mg/m(2) doxorubicin, and 1.4 mg/m(2) (maximum 2 ...

journal_title：Investigational new drugs

authors： Kim SJ,Kang HJ,Kim JS,Eom HS,Huh J,Ko YH,Lee J,Yim DS,Lee SY,Park WS,Yang WI,Lee SS,Suh C,Kim WS

更新日期：2013-12-01 00:00:00

abstract：:We investigated proliferation and apoptosis induction in Jurkat T-leukemia cells by the new isothiocyanate 4-(methylthio)butylisothiocyanate (MTBITC). To help elucidate whether the effects of MTBITC are specific for cancer cells, we tested MTBITC on freshly isolated, non-transformed human peripheral T lymphocytes. The...

journal_title：Investigational new drugs

authors： Fimognari C,Nüsse M,Iori R,Cantelli-Forti G,Hrelia P

更新日期：2004-04-01 00:00:00

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

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

abstract：:L1210 leukemia cells, because of their rapid growth rate in suspension culture and high growth fraction, are ideally suited to screen in vitro for cytotoxic compounds. Although L1210 cells may mimic rapidly growing tumors, they have not been effective in selecting agents active against slow growing solid tumors. We ex...

journal_title：Investigational new drugs

authors： Badiner GJ,Hamilton RD,Li LH,Bhuyan BK

更新日期：1987-01-01 00:00:00