当前位置： SCI文献检索 > INVESTIGATIONAL NEW DRUGS期刊下所有文献 > A phase I trial of combination trastuzumab, lapatinib, and bevacizumab in patients with advanced cancer.

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 for responding tumor types). Patients received lapatinib daily for 21 days, and bevacizumab and trastuzumab every 3 weeks. Correlates included HER2 extracellular domain levels (ECD) and single nucleotide polymorphisms (SNPs). RESULTS:Ninety-four patients were treated (median = four prior systemic therapies). The most common related adverse events ≥ grade 2 were diarrhea (n = 33, 35 %) and hypertension (n = 10, 11 %). The recommended phase 2 dose was trastuzumab 6 mg/m(2) (loading = 8 mg/m(2)) and bevacizumab 15 mg/kg every 3 weeks, with lapatinib 1,250 mg daily (full FDA-approved dose of each drug). One patient (1 %) achieved a complete response (CR); eight (9 %), a partial response (PR) (includes breast (n = 7, one of which was HER2 2+ by IHC) and salivary ductal carcinoma (n = 1); and 14 (15 %), stable disease (SD) ≥6 months (total SD ≥ 6 months/PR/CR =23 (25 %). All patients with PR/CR received prior trastuzumab +/- lapatinib. SD ≥ 6 months/PR/CR rate and time to treatment failure (TTF) correlated with elevated baseline HER2 ECD (N = 75 patients tested) but not with HER2 SNPs. CONCLUSIONS:Combination trastuzumab, lapatinib, and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with advanced malignancy.

journal_name

Invest New Drugs

journal_title

Investigational new drugs

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

doi

10.1007/s10637-014-0173-7

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

177-86

issue

1

eissn

0167-6997

issn

1573-0646

journal_volume

33

pub_type

杂志文章

相关文献

INVESTIGATIONAL NEW DRUGS文献大全
  • In vitro activity of 4'-iodo-4'-deoxydoxorubicin on human colo-rectal cancer as measured by a short-term antimetabolic assay.

    abstract：:A short-term antimetabolic assay based upon the inhibition of incorporation of nucleic acid precursors was used to compare the cytotoxicity of a new halogenated anthracycline, 4'-iodo-4'-deoxydoxorubicin (IDX), with that of its parent compound doxorubicin (DX) on human colo-rectal carcinoma specimens. IDX showed a mar...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00177248

    authors： Villa R,Zaffaroni N,Giuliani F,Colella G,Sanfilippo O,Silvestrini R

    更新日期：1990-05-01 00:00:00

  • Matrix metalloproteinase inhibitors.

    abstract：:The matrix metalloproteinases (MMPs) are a family of at least fifteen secreted and membrane-bound zinc-endopeptidases. Collectively, these enzymes can degrade all of the components of the extracellular matrix, including fibrallar and non-fibrallar collagens, fibronectin, laminin and basement membrane glycoproteins. MM...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,评审

    doi：10.1023/a:1005722729132

    authors： Wojtowicz-Praga SM,Dickson RB,Hawkins MJ

    更新日期：1997-01-01 00:00:00

  • The flavonoid luteolin suppresses infantile hemangioma by targeting FZD6 in the Wnt pathway.

    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

    pub_type： 杂志文章

    doi：10.1007/s10637-020-01052-8

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

    更新日期：2021-01-07 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

    doi：10.1007/BF00179430

    authors： Litterst CL,Roth JS,Kelley JA

    更新日期：1985-01-01 00:00:00

  • A phase I study of vitamin E, 5-fluorouracil and leucovorin for advanced malignancies.

    abstract：:Six patients with incurable malignancies were originally treated with vitamin E, 3200 IU/day for fourteen days, followed by the same dose of vitamin E daily plus LCV (20 mg/m2 i.v. bolus daily x 5) with 5FU (425 mg/m2 i.v. bolus immediately following LCV). The same schedule of LCV and 5FU was repeated 4 weeks later, t...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1023/a:1006484031959

    authors： Blanke CD,Stipanov M,Morrow J,Rothenberg M,Chinery R,Shyr Y,Coffey R,Johnson DH,Leach SD,Beauchamp RD

    更新日期：2001-01-01 00:00:00

  • Mononuclear cell polyamine content associated with myeloid maturation in patients with leukemia during administration of polyamine inhibitors.

    abstract：:Fourteen patients with acute leukemia in relapse were treated with difluoromethylornithine (DFMO) alone or in combination with methylglyoxal-bis(guanylhydrazone) (MGBG) as part of Phase I studies. Five patients included in the trial exhibited morphologic evidence of cellular differentiation during the course of treatm...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00170848

    authors： Maddox AM,Keating MJ,Freireich EJ,Haddox MK

    更新日期：1989-07-01 00:00:00

  • Discovery of LY2457546: a multi-targeted anti-angiogenic kinase inhibitor with a novel spectrum of activity and exquisite potency in the acute myelogenous leukemia-Flt-3-internal tandem duplication mutant human tumor xenograft model.

    abstract：:LY2457546 is a potent and orally bioavailable inhibitor of multiple receptor tyrosine kinases involved in angiogenic and tumorigenic signalling. In biochemical and cellular assays, LY2457546 demonstrates potent activity against targets that include VEGFR2 (KDR), PDGFRβ, FLT-3, Tie-2 and members of the Eph family of re...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-011-9640-6

    authors： Burkholder TP,Clayton JR,Rempala ME,Henry JR,Knobeloch JM,Mendel D,McLean JA,Hao Y,Barda DA,Considine EL,Uhlik MT,Chen Y,Ma L,Bloem LJ,Akunda JK,McCann DJ,Sanchez-Felix M,Clawson DK,Lahn MM,Starling JJ

    更新日期：2012-06-01 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

    doi：10.1023/a:1023525513696

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

    更新日期：2003-05-01 00:00:00

  • Synthesis, characterization, and evaluation of Cd[L-proline]2, a novel histone deacetylase inhibitor that induces epigenetic modification of histone deacetylase isoforms in A549 cells.

    abstract：:Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression through their effects on the compact chromatin structure. In clinical studies, several classes of histone deacetylase inhibitors (HDACi) have demonstrated potent anticancer activities with metal complexes. Hence, we syn...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-017-0489-1

    authors： Chidambaram A,Sekar A,S H K,Chidambaram RK,Arunachalam K,G P S,Vilwanathan R

    更新日期：2017-12-01 00:00:00

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

    abstract：: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 Meth...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-015-0221-y

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

    更新日期：2015-06-01 00:00:00

  • Effectiveness of cetuximab as preemptive postsurgical therapy for oral squamous cell carcinoma patients with major risk: a single-center retrospective cohort study.

    abstract：:A retrospective cohort study was performed to investigate the effectiveness of preemptive postsurgical therapy with cetuximab for patients with a major risk of recurrence or metastasis after clinical complete resection of primary oral squamous cell carcinoma (OSCC). The study period was from 2007 to 2019 for patients ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-021-01062-0

    authors： Fukumoto C,Sawatani Y,Shiraishi R,Zama M,Shimura M,Hasegawa T,Komiyama Y,Fujita A,Wakui T,Kawamata H

    更新日期：2021-01-15 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

    doi：10.1007/s10637-014-0110-9

    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

  • 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

    doi：10.1007/s10637-015-0284-9

    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

  • Spirogermanium: a new investigational drug of novel structure and lack of bone marrow toxicity.

    abstract：:Spirogermanium (NSC 192965) is a new metallic investigational anticancer drug of novel heterocyclic structure. Although its mode of action has not been fully elucidated, it appears that spirogermanium is not a phase or cell cycle specific drug and inhibits DNA, RNA and protein synthesis, the protein synthesis being th...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00208894

    authors： Slavik M,Blanc O,Davis J

    更新日期：1983-01-01 00:00:00

  • The effect of a novel frizzled 8-related antiproliferative factor on in vitro carcinoma and melanoma cell proliferation and invasion.

    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

    pub_type： 杂志文章

    doi：10.1007/s10637-011-9746-x

    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

  • Phase I study of weekly plitidepsin as 1-hour infusion combined with carboplatin in patients with advanced solid tumors or lymphomas.

    abstract：:This dose-escalating phase I clinical trial was designed to determine the recommended dose (RD) and to assess the safety and feasibility of weekly plitidepsin (1-hour i.v. infusion, Days 1, 8 and 15) combined with carboplatin (1-hour i.v. infusion, Day 1, after plitidepsin) in 4-week (q4wk) cycles given to patients wi...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-010-9488-1

    authors： Salazar R,Plummer R,Oaknin A,Robinson A,Pardo B,Soto-Matos A,Yovine A,Szyldergemajn S,Calvert AH

    更新日期：2011-12-01 00:00:00

  • Phase II study of esorubicin (4'-deoxydoxorubicin) in advanced epithelial carcinoma of the ovary: a Gynecologic Oncology Group study.

    abstract：:Twenty-six patients with advanced, measurable epithelial carcinoma of the ovary were treated with 76 courses of esorubicin at doses ranging from 20-30 mg/m2 every 3 weeks. All patients are evaluable for toxicity and response. All patients had received prior therapy including radiation therapy in 9, non-anthracycline c...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00173763

    authors： McGuire WP,Blessing JA,Berman ML

    更新日期：1989-11-01 00:00:00

  • Flutamide in unresectable pancreatic adenocarcinoma: a randomized, double-blind, placebo-controlled trial.

    abstract：PURPOSE:To evaluate the impact of flutamide on survival of patients with unresectable pancreatic cancer. METHODS:This single institution, randomized, double-blind, placebo controlled study compared flutamide in the dose of 250 mg three times daily (n = 23) versus placebo (n = 23) in patients with histologically proven...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,随机对照试验

    doi：10.1007/s10637-005-3536-2

    authors： Negi SS,Agarwal A,Chaudhary A

    更新日期：2006-05-01 00:00:00

  • Phase II trial of intravenous melphalan in advanced colorectal carcinoma.

    abstract：BACKGROUND:Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF00874443

    authors： Moore DF Jr,Pazdur R,Abbruzzese JL

    更新日期：1994-01-01 00:00:00

  • Phase I study of sunitinib plus S-1 and cisplatin in Japanese patients with advanced or metastatic gastric cancer.

    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

    pub_type： 杂志文章

    doi：10.1007/s10637-013-9948-5

    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

  • 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

  • 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

  • Matrix metalloproteinase inhibitors: present achievements and future prospects.

    abstract：:Matrix metalloproteinases (MMPs) are a class of structurally related enzymes that function in the degradation of extracellular matrix proteins that constitute the pericellular connective tissue and play an important role in both normal and pathological tissue remodelling. Increased MMP activity is detected in a wide r...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,评审

    doi：10.1023/a:1005855905442

    authors： Denis LJ,Verweij J

    更新日期：1997-01-01 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

    doi：10.1007/BF00216932

    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 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

    doi：10.1007/BF00873240

    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 trial of low-dose N-(phosphonacetyl)-disodium L-aspartic acid and high-dose 24-hour infusional 5-fluorouracil in advanced gastric adenocarcinoma. A Southwest Oncology Group study.

    abstract：:N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) follo...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF00180821

    authors： Martino RL,Fleming TR,Morrell LM,Ardalan B,Richman SP,Macdonald JS

    更新日期：1996-01-01 00:00:00

  • Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer.

    abstract：PURPOSE:This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. EXPERIMENTAL DESIGN:This was an open-label, multicenter, dose-escalation stu...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-012-9815-9

    authors： Weiss GJ,Donehower RC,Iyengar T,Ramanathan RK,Lewandowski K,Westin E,Hurt K,Hynes SM,Anthony SP,McKane S

    更新日期：2013-02-01 00:00:00

  • Effects of diflubenzuron and clanfenur on mouse bone marrow cells.

    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

    pub_type： 杂志文章

    doi：10.1007/BF00874426

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

    更新日期：1993-11-01 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

    doi：10.1007/s10637-019-00784-6

    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

  • 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