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


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.


Target Oncol


Targeted oncology


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




Has Abstract


2020-02-01 00:00:00














  • QTc prolongation induced by targeted biotherapies used in clinical practice and under investigation: a comprehensive review.

    abstract::In anticancer drug development, there has been increasing consideration for the potential of a compound to cause adverse electrocardiographic changes, especially QT interval prolongation, which can be associated with risk of torsades de pointes and sudden death. Irrespective of overt clinical toxicities, QTc assessmen...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Locatelli M,Criscitiello C,Esposito A,Minchella I,Goldhirsch A,Cipolla C,Curigliano G

    更新日期:2015-03-01 00:00:00

  • Prognostic significance of host immune status in patients with late relapsing renal cell carcinoma treated with targeted therapy.

    abstract::We aimed to assess the prognostic role of pretreatment neutrophilia, lymphocytopenia, and neutrophil to lymphocyte ratio (NLR) in patients treated with vascular endothelial growth factor-tyrosine kinase inhibitors (VEGFR-TKIs) for late relapsing (>5 years) metastatic renal cell carcinoma (mRCC). Data were collected fr...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Santoni M,Buti S,Conti A,Porta C,Procopio G,Sternberg CN,Bracarda S,Basso U,De Giorgi U,Rizzo M,Derosa L,Ortega C,Massari F,Milella M,Bersanelli M,Cerbone L,Muzzonigro G,Burattini L,Montironi R,Santini D,Cascinu S

    更新日期:2015-12-01 00:00:00

  • Phase I Study of Irinotecan/5-Fluorouracil/Leucovorin (FOLFIRI) with Sunitinib for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma.

    abstract:BACKGROUND:Sunitinib (S) is a multi-targeted tyrosine kinase inhibitor. It is synergistic with chemotherapy in preclinical models. We hypothesized that sunitinib in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) would be a tolerable and effective regimen in advanced gastric and gastroesophageal jun...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Mukherjee S,Fountzilas C,Boland PM,Gosain R,Attwood K,Tan W,Khushalani N,Iyer R

    更新日期:2020-02-01 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


    authors: Keating GM

    更新日期:2017-04-01 00:00:00

  • Serum Alpha1-Globulin as a Novel Prognostic Factor in Metastatic Renal Cell Carcinoma Treated with Tyrosine Kinase Inhibitors.

    abstract:BACKGROUND:Serum protein fraction (SPF) is a common parameter reflecting the nutritional and inflammatory status of the human body. However, its role in patients with cancer, particularly those treated with targeted agents, is unknown. OBJECTIVE:We conducted this study to explore the prognostic value of SPF in patient...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Chen X,Yao J,Liu L,Zheng W,Hu X,Zhu Y,Wang H,Guo J

    更新日期:2019-04-01 00:00:00

  • 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


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

    更新日期:2010-03-01 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


    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

  • 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


    authors: Planchard D

    更新日期:2013-03-01 00:00:00

  • Low Baseline Serum Sodium Concentration Is Associated with Poor Clinical Outcomes in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy.

    abstract:BACKGROUND:A consistent percentage of patients with metastatic non-small cell lung cancer (NSCLC) derives no or only marginal benefit from immunotherapy (IO). OBJECTIVE:Since serum sodium has been linked to both prognosis in NSCLC and modulation of immune cells activity, we aimed to assess the association between low ...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Fucà G,Galli G,Poggi M,Lo Russo G,Proto C,Imbimbo M,Vitali M,Ganzinelli M,Lanti C,Molino G,Stangoni F,Zilembo N,de Braud F,Garassino MC,Signorelli D

    更新日期:2018-12-01 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


    authors: Snider KL,Maitland ML

    更新日期:2009-04-01 00:00:00

  • EGFR intron-1 CA repeat polymorphism is a predictor of relapse and survival in complete resected only surgically treated esophageal cancer.

    abstract::Basal transcription regulation of the epidermal growth factor receptor is dependent upon a CA simple sequence repeat polymorphism in the intron-1 (CA-SSR-1). Here, we evaluate the role of CA-SSR-1 in complete resected esophageal cancer (EC) patients without neoadjuvant or adjuvant treatment. Genomic DNA was extracted ...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Vashist YK,Trump F,Gebauer F,Kutup A,Güngör C,Kalinin V,Muddasar R,Vettorazzi E,Yekebas EF,Brandt B,Pantel K,Izbicki JR

    更新日期:2014-03-01 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


    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

  • The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review.

    abstract::Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker a...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Nichetti F,Marra A,Corti F,Guidi A,Raimondi A,Prinzi N,de Braud F,Pusceddu S

    更新日期:2018-06-01 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


    authors: Demicheli R

    更新日期:2013-06-01 00:00:00

  • Expression and activity of EGFR in human cutaneous melanoma cell lines and influence of vemurafenib on the EGFR pathway.

    abstract::Data regarding the expression of epidermal growth factor receptor (EGFR) in melanoma and its role in the tumor biology are conflicting. In BRAF V600-mutant melanomas, the expression of EGFR has been associated with acquired resistance to BRAF inhibitors. In this study, we assessed EGFR expression and downstream signal...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Gross A,Niemetz-Rahn A,Nonnenmacher A,Tucholski J,Keilholz U,Fusi A

    更新日期:2015-03-01 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


    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

  • Totality of Scientific Evidence in the Development of ABP 980, a Biosimilar to Trastuzumab.

    abstract::ABP 980 was developed as a biosimilar to trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), that is indicated for the treatment of HER2-positive metastatic breast cancer, early breast cancer (EBC), and metastatic gastric cancer. ABP 980 is approved in the United States, Europ...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Kolberg HC,Colleoni M,Santi P,Demetriou GS,Segui-Palmer MA,Fujiwara Y,Hurvitz SA,Hanes V

    更新日期:2019-12-01 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


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

    更新日期:2015-12-01 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


    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

  • 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


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

    更新日期:2020-06-01 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


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

    更新日期:2014-09-01 00:00:00

  • Combinatorial Study of a Novel Poly (ADP-ribose) Polymerase Inhibitor and an HDAC Inhibitor, SAHA, in Leukemic Cell Lines.

    abstract:BACKGROUND:Cancer is a multifactorial disease, which makes it difficult to cure. Since more than one defective cellular component is often involved during oncogenesis, combination therapy is gaining prominence in the field of cancer therapeutics. OBJECTIVE:The purpose of this study was to investigate the combinatorial...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Hegde M,Mantelingu K,Pandey M,Pavankumar CS,Rangappa KS,Raghavan SC

    更新日期:2016-10-01 00:00:00

  • Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial.

    abstract::The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) inv...

    journal_title:Targeted oncology

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Heigener DF,Pereira JR,Felip E,Mazal J,Manzyuk L,Tan EH,Merimsky O,Sarholz B,Esser R,Gatzemeier U

    更新日期:2015-06-01 00:00:00

  • Ongoing Response in BRAF V600E-Mutant Melanoma After Cessation of Intermittent Vemurafenib Therapy: A Case Report.

    abstract::The selective BRAF inhibitors vemurafenib and dabrafenib yield high response rates and improved overall survival in patients with BRAF V600E-mutant metastatic melanoma. Treatment traditionally continues until disease progression or the development of unacceptable toxicity. Acquired drug resistance and toxicity are key...

    journal_title:Targeted oncology

    pub_type: 杂志文章


    authors: Dooley AJ,Gupta A,Middleton MR

    更新日期:2016-08-01 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


    authors: Driscoll JJ,Dechowdhury R

    更新日期:2010-12-01 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


    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

  • 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


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

    更新日期:2009-12-01 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


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

    更新日期:2012-12-01 00:00:00

  • The Multifaceted Roles of B Cells in Solid Tumors: Emerging Treatment Opportunities.

    abstract::The influence of tumor infiltrating lymphocytes on tumor growth and response to therapy is becoming increasingly apparent. While much work has focused on the role of T cell responses in anti-tumor immunity, the role of B cells in solid tumors is much less understood. Tumor infiltrating B cells have been found in a var...

    journal_title:Targeted oncology

    pub_type: 杂志文章,评审


    authors: Flynn NJ,Somasundaram R,Arnold KM,Sims-Mourtada J

    更新日期:2017-04-01 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


    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