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 challenges with the use of these drugs. Resistance to vemurafenib usually develops within 6-8 months. Management of drug toxicity typically involves stopping vemurafenib until resolution, before restarting at a lower dose, or permanently ceasing vemurafenib therapy. We have recently considered whether intermittent dosing could be used as an alternative to dose reduction/termination in the management of vemurafenib toxicity. One patient treated with intermittent vemurafenib was an 89-year-old woman with metastatic melanoma, who initially showed a good response to continuous dosing. Recurrent toxicity meant that the continuous vemurafenib dosage was repeatedly ceased before restarting at a lower dose. Ten months after vemurafenib was first begun, an intermittent dosing regimen was introduced in an attempt to control toxicity. This continued for 2 months, before cessation due to continued unacceptable toxicity. A further 24 months later, the patient remains fit and well in complete clinical remission, with no recurrence of her previous melanoma and no new primary malignancies. To the best of our knowledge, a continued response after the cessation of selective BRAF inhibitors has never before been described in melanoma. Induction of an immune response and/or epigenetic changes could explain continued disease response after cessation of vemurafenib therapy. Care should be taken when extrapolating the findings from the continued response after vemurafenib cessation to other tumour types. We recommend the collection and analysis of data to investigate the clinical responses seen after cessation of vemurafenib due to intolerable toxicities, which could help further explain vemurafenib's mechanism of action.
journal_name
Target Oncoljournal_title
Targeted oncologyauthors
Dooley AJ,Gupta A,Middleton MRdoi
10.1007/s11523-015-0410-9subject
Has Abstractpub_date
2016-08-01 00:00:00pages
557-63issue
4eissn
1776-2596issn
1776-260Xpii
10.1007/s11523-015-0410-9journal_volume
11pub_type
杂志文章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
更新日期:2019-10-01 00:00:00
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
doi:10.1007/s11523-013-0260-2
更新日期:2014-03-01 00:00:00
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
更新日期:2010-03-01 00:00:00
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
更新日期:2019-04-01 00:00:00
abstract::Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignancy with poor outcome occurring in adolescents and young adults. Therapeutic options for patients with advanced disease are limited. Preclinical studies have shown that VEGFR-2 and VEGFA are overexpressed in DSRCT and that DSRCT xenografts wer...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-012-0251-8
更新日期:2013-09-01 00:00:00
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
更新日期:2015-12-01 00:00:00
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
doi:10.1007/s11523-019-00692-y
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:Immune checkpoint inhibitors (ICIs) demonstrated improved overall survival (OS) in heavily pretreated unselected patients with metastatic gastro-esophageal junction (mGOJ)/gastric cancer (GC). Attempts to select patients based on programmed death-ligand 1 (PD-L1) expression appear to be suboptimal. A strong ...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-020-00723-z
更新日期:2020-06-01 00:00:00
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
更新日期:2012-12-01 00:00:00
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
doi:10.1007/s11523-019-00625-9
更新日期:2019-04-01 00:00:00
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 wi...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-020-00701-5
更新日期:2020-02-01 00:00:00
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
更新日期:2018-12-01 00:00:00
abstract::Chemotherapy represents the mainstay of non-small cell lung cancer (NSCLC) treatment, but response is usually observed in only one out of three patients. Massive efforts have been carried out to identify biomarkers that might help clinicians to choose appropriate drugs, by identifying potentially sensitive subjects an...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-010-0132-y
更新日期:2010-03-01 00:00:00
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
更新日期:2016-02-01 00:00:00
abstract:BACKGROUND:Hypovitaminosis D is associated with an adverse prognosis in colon cancer patients, possibly due to the effects of the vitamin on the immune system. Antibody-dependent cell-mediated cytotoxicity (ADCC) significantly contributes to the anti-tumor effects of monoclonal antibodies, including cetuximab, an epide...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-018-0586-x
更新日期:2018-10-01 00:00:00
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
更新日期:2009-04-01 00:00:00
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
更新日期:2012-06-01 00:00:00
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
更新日期:2016-08-01 00:00:00
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
更新日期:2010-12-01 00:00:00
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
更新日期:2017-08-01 00:00:00
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
更新日期:2020-06-01 00:00:00
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
更新日期:2012-12-01 00:00:00
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
doi:10.1007/s11523-018-0567-0
更新日期:2018-06-01 00:00:00
abstract:OBJECTIVE:To determine the efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in molecularly selected patients with advanced non-small cell lung cancer (NSCLC), we performed this pooled analysis. METHOD:Randomized trials of EGFR-TKIs as treatment for advanced NSCLC wer...
journal_title:Targeted oncology
pub_type: 杂志文章,meta分析,收录出版
doi:10.1007/s11523-015-0376-7
更新日期:2016-02-01 00:00:00
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
更新日期:2016-04-01 00:00:00
abstract::Elderly and poor performance status advanced non-small cell lung cancer (NSCLC) patients often tolerate chemotherapy poorly. Special approaches are needed for these patient populations. Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), erlotinib and gefitinib, are active agents in the t...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-009-0104-2
更新日期:2009-01-01 00:00:00
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
doi:10.1007/s11523-017-0481-x
更新日期:2017-04-01 00:00:00
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
更新日期:2020-06-01 00:00:00
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
更新日期:2018-08-01 00:00:00
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
更新日期:2012-12-01 00:00:00