Safety, Pharmacokinetics, and Clinical Activity of Adavosertib in Combination with Chemotherapy in Asian Patients with Advanced Solid Tumors: Phase Ib Study.

Abstract:

BACKGROUND:The WEE1 inhibitor adavosertib (AZD1775) has been investigated in Western patients. OBJECTIVE:This open-label Phase Ib study (NCT02341456) investigated the safety, pharmacokinetics, and clinical activity of adavosertib in combination with carboplatin alone or paclitaxel plus carboplatin in Asian patients with advanced solid tumors and defined the recommended Phase II dose. PATIENTS AND METHODS:Nineteen patients received adavosertib 175 mg twice daily (bid) for 2.5 days (five doses) in combination with carboplatin (AUC 5) alone or paclitaxel (175 mg/m2) plus carboplatin, or adavosertib 225 mg bid for 2.5 days in combination with paclitaxel plus carboplatin in 21-day cycles. Preliminary safety and dose-limiting toxicity analyses were performed and dose escalation/de-escalation conducted as appropriate. RESULTS:Adavosertib 175 mg bid for 2.5 days with carboplatin alone or paclitaxel plus carboplatin was considered tolerable. Two patients receiving adavosertib 225 mg bid in combination with paclitaxel plus carboplatin experienced dose-limiting toxicities (grade 4 sepsis; grade 5 acute respiratory distress syndrome); this regimen was not considered tolerable. Grade ≥ 3 adverse events reported most commonly in any cohort included: anemia; decreased white blood cell count; decreased neutrophil count; neutropenia; decreased platelet count; thrombocytopenia; and febrile neutropenia. Exposure to adavosertib, as determined by pharmacokinetic analysis, in Asian patients was higher than that previously seen in Western patients. A partial response occurred in 2/12 evaluable patients (16.7%) at the recommended Phase II dose. CONCLUSIONS:Adavosertib 175 mg bid for 2.5 days was chosen as the recommended Phase II dose in combination with paclitaxel and carboplatin in Asian patients.

journal_name

Target Oncol

journal_title

Targeted oncology

authors

Kato H,de Souza P,Kim SW,Lickliter JD,Naito Y,Park K,Kumar S,Mugundu GM,Bang YJ

doi

10.1007/s11523-020-00701-5

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

75-84

issue

1

eissn

1776-2596

issn

1776-260X

pii

10.1007/s11523-020-00701-5

journal_volume

15

pub_type

杂志文章
  • Dynamic contrast-enhanced ultrasonography (DCE-US): a new tool for the early evaluation of antiangiogenic treatment.

    abstract::Dynamic contrast-enhanced ultrasonography (DCE-US) is a new functional technique enabling a quantitative assessment of solid tumor perfusion using raw linear data. DCE-US allows the calculation of parameters as slope of wash-in or area under the curve (AUC) representing, respectively, blood flow or blood volume. Reduc...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-010-0136-7

    authors: Lassau N,Chebil M,Chami L,Bidault S,Girard E,Roche A

    更新日期:2010-03-01 00:00:00

  • Targeting Met and VEGFR Axis in Metastatic Castration-Resistant Prostate Cancer: 'Game Over'?

    abstract::Despite recent advances that have been made in the therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC), effective management of bone metastases remains a key goal not yet reached. The receptor tyrosine kinase MET and the vascular endothelial growth factor receptor (VEGFR) seem to play an i...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-015-0412-7

    authors: Modena A,Massari F,Ciccarese C,Brunelli M,Santoni M,Montironi R,Martignoni G,Tortora G

    更新日期:2016-08-01 00:00:00

  • Designs and challenges for personalized medicine studies in oncology: focus on the SHIVA trial.

    abstract::Personalized medicine is defined by the National Cancer Institute as "a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, and treat disease." In oncology, the term "personalized medicine" arose with the emergence of molecularly targeted agents. The prescript...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-012-0237-6

    authors: Le Tourneau C,Kamal M,Trédan O,Delord JP,Campone M,Goncalves A,Isambert N,Conroy T,Gentien D,Vincent-Salomon A,Pouliquen AL,Servant N,Stern MH,Le Corroller AG,Armanet S,Rio Frio T,Paoletti X

    更新日期:2012-12-01 00:00:00

  • Acquired Resistance to Erlotinib in EGFR Mutation-Positive Lung Adenocarcinoma among Hispanics (CLICaP).

    abstract:BACKGROUND:Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE:The purpose of this study was to assess...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-017-0497-2

    authors: Cardona AF,Arrieta O,Zapata MI,Rojas L,Wills B,Reguart N,Karachaliou N,Carranza H,Vargas C,Otero J,Archila P,Martín C,Corrales L,Cuello M,Ortiz C,Pino LE,Rosell R,Zatarain-Barrón ZL,CLICaP.

    更新日期:2017-08-01 00:00:00

  • Therapeutically targeting the SUMOylation, Ubiquitination and Proteasome pathways as a novel anticancer strategy.

    abstract::The ubiquitin (Ub)+proteasome proteolytic pathway is responsible for the selective degradation of the majority of nuclear and cytosolic proteins. The proteasome is a high molecular weight multicatalytic protease that serves as the catalytic core of the complex Ub-dependent protein degradation pathway and is an excitin...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-010-0165-2

    authors: Driscoll JJ,Dechowdhury R

    更新日期:2010-12-01 00:00:00

  • Targeting insulin-like growth factor type 1 receptor in cancer therapy.

    abstract::It is believed that the insulin-like growth factor receptor type 1 (IGF-1R) signaling pathway plays a pivotal role in cancer growth, progression, and resistance to anticancer therapies. Strategies are being developed to block IGF-1R as an anticancer treatment. We reviewed several potential strategies for disrupting th...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-009-0123-z

    authors: Atzori F,Traina TA,Ionta MT,Massidda B

    更新日期:2009-12-01 00:00:00

  • Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia.

    abstract::Venetoclax (Venclyxto®; Venclexta®) is a first-in-class, oral, selective B cell lymphoma-2 (BCL-2) inhibitor. The drug is approved in numerous countries, including those of the EU and in the USA, for the treatment of adults with relapsed or refractory (RR) chronic lymphocytic leukemia (CLL); the specific indication(s)...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-019-00673-1

    authors: Scott LJ

    更新日期:2019-10-01 00:00:00

  • Hyperbaric oxygen therapy and cancer--a review.

    abstract::Hypoxia is a critical hallmark of solid tumors and involves enhanced cell survival, angiogenesis, glycolytic metabolism, and metastasis. Hyperbaric oxygen (HBO) treatment has for centuries been used to improve or cure disorders involving hypoxia and ischemia, by enhancing the amount of dissolved oxygen in the plasma a...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-012-0233-x

    authors: Moen I,Stuhr LE

    更新日期:2012-12-01 00:00:00

  • Tumor Mutation Burden as a Potential Biomarker for PD-1/PD-L1 Inhibition in Advanced Non-small Cell Lung Cancer.

    abstract:BACKGROUND:Immunotherapy based on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has revolutionized the treatment of non-small cell lung cancer (NSCLC). Patients with high PD-L1 expression or DNA mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) cancer are re...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-020-00703-3

    authors: Huang D,Zhang F,Tao H,Zhang S,Ma J,Wang J,Liu Z,Cui P,Chen S,Huang Z,Wu Z,Zhao L,Hu Y

    更新日期:2020-02-01 00:00:00

  • Pralatrexate in Chinese Patients with Relapsed or Refractory Peripheral T-cell Lymphoma: A Single-arm, Multicenter Study.

    abstract:BACKGROUND:Peripheral T-cell lymphoma (PTCL) is associated with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. Pralatrexate, a folate analogue inhibitor, was the first drug approved to treat R/R PTCL. OBJECTIVE:As the distribution of PTCL subtypes differs between populations and few p...

    journal_title:Targeted oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s11523-019-00630-y

    authors: Hong X,Song Y,Huang H,Bai B,Zhang H,Ke X,Shi Y,Zhu J,Lu G,Liebscher S,Cai C

    更新日期:2019-04-01 00:00:00

  • Chronic therapy in gastrointestinal stromal tumours (GISTs): the big gap between theory and practice.

    abstract::The advent of imatinib mesilate, an oral target therapy, has dramatically changed the natural history of gastrointestinal stromal tumours (GISTs). This rare neoplasm has become the paradigm of targeted therapies in solid tumours, also introducing a home-based cure concept in oncology. However, it should be retained th...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-012-0221-1

    authors: Saponara M,Pantaleo MA,Nannini M,Biasco G

    更新日期:2012-12-01 00:00:00

  • Inflammatory Indexes as Prognostic and Predictive Factors in Ovarian Cancer Treated with Chemotherapy Alone or Together with Bevacizumab. A Multicenter, Retrospective Analysis by the MITO Group (MITO 24).

    abstract:BACKGROUND:The variability in progression-free survival (PFS) and overall survival (OS) among patients with epithelial ovarian cancer (EOC) makes it difficult to reliably predict outcomes. A predictive biomarker of bevacizumab efficacy as first-line therapy in EOC is still lacking. OBJECTIVE:The MITO group conducted a...

    journal_title:Targeted oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s11523-018-0574-1

    authors: Farolfi A,Petrone M,Scarpi E,Gallà V,Greco F,Casanova C,Longo L,Cormio G,Orditura M,Bologna A,Zavallone L,Ventriglia J,Franzese E,Loizzi V,Giardina D,Pigozzi E,Cioffi R,Pignata S,Giorda G,De Giorgi U

    更新日期:2018-08-01 00:00:00

  • Imaging response in neuroendocrine tumors treated with targeted therapies: the experience of sunitinib.

    abstract::Among neuroendocrine carcinomas of the gut, well-differentiated tumors are highly vascularized, featuring specific characteristics on contrast-enhanced imaging. Well-differentiated neuroendocrine tumors spontaneously harbor hypervascular enhancement, coexisting with areas of necrosis mainly located at the center of tu...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-012-0216-y

    authors: Faivre S,Ronot M,Dreyer C,Serrate C,Hentic O,Bouattour M,Bruno O,Couvelard A,Vilgrain V,Raymond E

    更新日期:2012-06-01 00:00:00

  • Targeting multiple oncogenic pathways for the treatment of hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer diagnosed worldwide. HCC occurs due to chronic liver disease and is often diagnosed at advanced stages. Chemotherapeutic agents such as doxorubicin are currently used as first-line agents for HCC therapy, but these are non-selective cytotox...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-016-0452-7

    authors: Swamy SG,Kameshwar VH,Shubha PB,Looi CY,Shanmugam MK,Arfuso F,Dharmarajan A,Sethi G,Shivananju NS,Bishayee A

    更新日期:2017-02-01 00:00:00

  • Tumours and tissues: similar homeostatic systems?

    abstract::The currently prevalent somatic mutation theory of carcinogenesis and metastases explicitly assumes that cancer is a cellular disease, i.e. a disease of the control of cell proliferation and/or cell differentiation. Accordingly, explanations should always be sought for at a gene and/or gene product level, regardless o...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-013-0277-6

    authors: Demicheli R

    更新日期:2013-06-01 00:00:00

  • Impact of the Neutrophil-to-Lymphocyte Ratio on the Survival of Patients with Gastric Cancer Treated with Nivolumab Monotherapy.

    abstract:BACKGROUND:In 2017, nivolumab monotherapy was shown to be effective as third- or later-line therapy in patients with advanced gastric or gastroesophageal junction cancer. OBJECTIVE:In this study, we investigated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the outcomes of nivolumab monotherapy...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-020-00716-y

    authors: Yamada T,Hayashi T,Inokuchi Y,Hayashi K,Watanabe H,Komori K,Kano K,Shimoda Y,Fujikawa H,Shiozawa M,Morinaga S,Rino Y,Masuda M,Ogata T,Oshima T

    更新日期:2020-06-01 00:00:00

  • Gemcitabine Combined with the mTOR Inhibitor Temsirolimus in Patients with Locally Advanced or Metastatic Pancreatic Cancer. A Hellenic Cooperative Oncology Group Phase I/II Study.

    abstract:BACKGROUND:The prognosis of patients with advanced pancreatic cancer is dismal, and there is a need for novel and effective treatments. OBJECTIVES:Tο determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a novel gemcitabine (G) and temsirolimus (T) combination (phase I) and estimate the 6-m...

    journal_title:Targeted oncology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1007/s11523-018-0605-y

    authors: Karavasilis V,Samantas E,Koliou GA,Kalogera-Fountzila A,Pentheroudakis G,Varthalitis I,Linardou H,Rallis G,Skondra M,Papadopoulos G,Papatsibas G,Sgouros J,Goudopoulou A,Kalogeras KT,Dervenis C,Pectasides D,Fountzilas G

    更新日期:2018-12-01 00:00:00

  • Vemurafenib-induced progression of breast cancer: a case report and review of the literature.

    abstract::Vemurafenib, a specific inhibitor of mutated BRAF kinase, may activate wild-type BRAF and therefore induce squamous cell skin carcinomas in patients treated for melanoma. All vemurafenib clinical trials excluded patients with multiple primary malignant tumors; therefore, the action of this drug on concurrent BRAF wild...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-015-0384-7

    authors: Novik AV,Protsenko SA,Baldueva IA,Ivantsov AO,Nekhaeva TL,Akhaeva ZY,Yanus GA,Iyevleva AG,Imyanitov EN

    更新日期:2016-04-01 00:00:00

  • Posterior reversible encephalopathy syndrome induced by anti-VEGF agents.

    abstract::Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity that may occur in patients receiving anti-vascular endothelial growth factor (VEGF) agents such as bevacizumab and tyrosine kinase inhibitors. Little is known about the characteristics of patients at risk for PRES under anti-VEGF agen...

    journal_title:Targeted oncology

    pub_type: 杂志文章,meta分析,评审

    doi:10.1007/s11523-011-0201-x

    authors: Tlemsani C,Mir O,Boudou-Rouquette P,Huillard O,Maley K,Ropert S,Coriat R,Goldwasser F

    更新日期:2011-12-01 00:00:00

  • A bispecific EpCAM/CD133-targeted toxin is effective against carcinoma.

    abstract::The discovery of chemoresistant cancer stem cells (CSCs) in carcinomas has created the need for therapies that specifically target these subpopulations of cells. Here, we characterized a bispecific targeted toxin that is composed of two antibody fragments and a catalytic protein toxin allowing it to bind two CSC marke...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-013-0290-9

    authors: Waldron NN,Barsky SH,Dougherty PR,Vallera DA

    更新日期:2014-09-01 00:00:00

  • Cardiovascular toxicities: clues to optimal administration of vascular endothelial growth factor signaling pathway inhibitors.

    abstract::Several angiogenesis inhibitors have been approved for commercial use and many additional agents are under development for the treatment of various malignancies. Cardiovascular toxicities have been increasingly recognized as effects of this entire class of new anticancer therapeutics. There is a limited but growing un...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-009-0106-0

    authors: Snider KL,Maitland ML

    更新日期:2009-04-01 00:00:00

  • Management of Adverse Events During Rucaparib Treatment for Relapsed Ovarian Cancer: A Review of Published Studies and Practical Guidance.

    abstract::The poly(ADP-ribose) polymerase inhibitor rucaparib is approved as monotherapy in the treatment and maintenance settings for women with relapsed ovarian cancer in the European Union and the United States. We review the safety profile of rucaparib in both settings and provide recommendations for the clinical management...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-020-00715-z

    authors: Lorusso D,García-Donas J,Sehouli J,Joly F

    更新日期:2020-06-01 00:00:00

  • Sorafenib: A Review in Hepatocellular Carcinoma.

    abstract::Sorafenib (Nexavar®) is currently the only systemic agent approved for use in hepatocellular carcinoma (HCC). Its approval was based on the results of the pivotal SHARP and Sorafenib Asia-Pacific (AP) trials in Child-Pugh (CP) class A patients with advanced HCC, which showed significantly longer median overall surviva...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-017-0484-7

    authors: Keating GM

    更新日期:2017-04-01 00:00:00

  • Renal Toxicities of Targeted Therapies.

    abstract::With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal tox...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审

    doi:10.1007/s11523-015-0368-7

    authors: Abbas A,Mirza MM,Ganti AK,Tendulkar K

    更新日期:2015-12-01 00:00:00

  • Is There a Survival Benefit of First-Line Epidermal Growth Factor Receptor Tyrosine-Kinase Inhibitor Monotherapy Versus Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer?: A Meta-Analysis.

    abstract:BACKGROUND:Tyrosine-kinase inhibitors (TKIs) markedly improve progression-free survival (PFS) of patients with advanced non-small-cell lung cancer (NSCLC) mutated for epidermal growth factor receptor (EGFR). Results on overall survival (OS) are less clear-cut. We performed a publication-based meta-analysis to address f...

    journal_title:Targeted oncology

    pub_type: 杂志文章,meta分析

    doi:10.1007/s11523-015-0373-x

    authors: Guetz GD,Landre T,Uzzan B,Chouahnia K,Nicolas P,Morere JF

    更新日期:2016-02-01 00:00:00

  • Effect of Renal Impairment on the Pharmacokinetics and Safety of Axitinib.

    abstract:BACKGROUND:Axitinib, an inhibitor of vascular endothelial growth factor (VEGF) receptors, is approved as second-line treatment for advanced renal cell carcinoma (RCC). Agents targeting the VEGF pathway may induce renal toxicities, which may be influenced by pre-existing renal dysfunction. OBJECTIVE:The objective was t...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-015-0389-2

    authors: Chen Y,Rini BI,Motzer RJ,Dutcher JP,Rixe O,Wilding G,Stadler WM,Tarazi J,Garrett M,Pithavala YK

    更新日期:2016-04-01 00:00:00

  • Detection of KIT and PDGFRA mutations in the plasma of patients with gastrointestinal stromal tumor.

    abstract::In subsets of gastrointestinal stromal tumors (GISTs), mutations of the KIT and PDGFRA receptor tyrosine kinases correlate with tumor prognosis and response to tyrosine kinase inhibitors (TKIs). Determining genotypes in TKI-resistant GISTs is challenging due to the potential risks and limitations of repeated biopsies ...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-015-0361-1

    authors: Kang G,Bae BN,Sohn BS,Pyo JS,Kang GH,Kim KM

    更新日期:2015-12-01 00:00:00

  • Targeted therapies in thyroid cancer.

    abstract::Differentiated thyroid carcinoma is the most frequent neoplasm of the endocrine system. Although thyroid cancer usually has an excellent prognosis, no therapeutic options are available for patients that develop metastases and are or became resistant to radioiodine therapy. The deeper knowledge of molecular aberrations...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-009-0124-y

    authors: Capdevila J,Perez-Garcia J,Obiols G,Tabernero J

    更新日期:2009-12-01 00:00:00

  • Identification of driver mutations in lung cancer: first step in personalized cancer.

    abstract::Non-small cell lung cancer (NSCLC) has recently been associated with interesting molecular characteristics that have important implications in carcinogenesis and response to targeted therapies. Targeted therapies, if given to a patient subpopulation enriched by the presence of relevant molecular targets, can often abr...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-013-0263-z

    authors: Planchard D

    更新日期:2013-03-01 00:00:00

  • Immunological Correlates of Response to Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma.

    abstract:BACKGROUND:The identification of prognostic and/or predictive biomarkers for response to immune checkpoint inhibitors (ICI) could help guide treatment decisions. OBJECTIVE:We assessed changes in programmed cell death-1 (PD1)/PD1 ligand (PDL1) expression in key immunomodulatory cell subsets (myeloid-derived suppressor ...

    journal_title:Targeted oncology

    pub_type: 杂志文章

    doi:10.1007/s11523-018-0595-9

    authors: Tzeng A,Diaz-Montero CM,Rayman PA,Kim JS,Pavicic PG Jr,Finke JH,Barata PC,Lamenza M,Devonshire S,Schach K,Emamekhoo H,Ernstoff MS,Hoimes CJ,Rini BI,Garcia JA,Gilligan TD,Ornstein MC,Grivas P

    更新日期:2018-10-01 00:00:00