empirical chemotherapy
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2021 ◽  
Vol 96 (5) ◽  
pp. 408-414
Author(s):  
Young Saing Kim ◽  
Soon Il Lee

Cancer of unknown primary (CUP) is a heterogenous group of cancers for which the anatomical site of origin is unidentifiable on the basis of standard evaluation and imaging. CUPs account for 2-5% of all malignancies and are characterized by early metastatic dissemination, aggressive clinical course, and poor response to palliative chemotherapy. It is important to identify favorable-risk CUP patients (10-20%), as they harbor chemo-sensitive and potentially curable tumors, and may require long-term disease control. Empirical combination chemotherapy has traditionally been the standard first-line therapy for most patients (80-90%), who do not belong to favorable-risk subsets; however, this approach has only modest benefits, with a median overall survival of < 1 year. Evidence supporting the clinical use of molecular tissue of origin (TOO) tests is still lacking. Two recent randomized clinical trials failed to show the benefit of TOO-based site-specific therapy over empirical chemotherapy. In an era of precision medicine, the use of comprehensive molecular profiling will provide opportunities to identify patient subsets who are susceptible to targeted therapies and immunotherapies.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247860
Author(s):  
Joyce H. S. You ◽  
William C. S. Cho ◽  
Wai-kit Ming ◽  
Yu-chung Li ◽  
Chung-kong Kwan ◽  
...  

Introduction Tyrosine kinase inhibitors (TKIs) therapy targets at epidermal growth factor receptor (EGFR) gene mutations in non-small-cell lung cancer (NSCLC). We aimed to compare the EGFR mutation-guided target therapy versus empirical chemotherapy for first-line treatment of advanced NSCLC in the public healthcare setting of Hong Kong. Methods A Markov model was designed to simulate outcomes of a hypothetical cohort of advanced (stage IIIB/IV) NSCLC adult patients with un-tested EGFR-sensitizing mutation status. Four treatment strategies were evaluated: Empirical first-line chemotherapy with cisplatin-pemetrexed (empirical chemotherapy group), and EGFR mutation-guided use of a TKI (afatinib, erlotinib, and gefitinib). Model outcome measures were direct medical cost, progression-free survival, overall survival, and quality-adjusted life-years (QALYs). Incremental cost per QALY gained (ICER) was estimated. Sensitivity analyses were performed to examine robustness of model results. Results Empirical chemotherapy and EGFR mutation-guided gefitinib gained lower QALYs at higher costs than the erlotinib group. Comparing with EGFR mutation-guided erlotinib, the afatinib strategy gained additional QALYs with ICER (540,633 USD/QALY). In 10,000 Monte Carlo simulations for probabilistic sensitivity analysis, EGFR mutation-guided afatinib, erlotinib, gefitinib and empirical chemotherapy were preferred strategy in 0%, 98%, 0% and 2% of time at willingness-to-pay (WTP) 47,812 USD/QALY (1x gross domestic product (GDP) per capita), and in 30%, 68%, 2% and 0% of time at WTP 143,436 USD/QALY (3x GDP per capita), respectively. Conclusions EGFR mutation-guided erlotinib appears to be the cost-effective strategy from the perspective of Hong Kong public healthcare provider over a broad range of WTP.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yosuke Mitani ◽  
Masashi Kanai ◽  
Tadayuki Kou ◽  
Shigeki Kataoka ◽  
Keitaro Doi ◽  
...  

Abstract Background Cancer of unknown primary (CUP) is usually treated with nonselective and empirical chemotherapy; however, its prognosis is generally poor, with a median survival of less than a year. Thus, clinicians eagerly await the development of more effective treatment strategies. In recent years, advances in next-generation sequencing (NGS) have made it possible to analyze comprehensively the genome of individual cancers. NGS has identified many genomic alterations, some of which are potential molecular targets of specific agents. We report a case of CUP that was successfully treated with targeted therapy directed by the genomic data obtained from an NGS-based multiplex assay. Case presentation A 52-year-old Asian woman with right hip joint pain underwent fluorodeoxyglucose-positron emission tomography/computed tomography, which showed multiple metastatic tumors in her right hip joint, thyroid gland, lung, and vertebrae. Brain magnetic resonance imaging showed multiple cerebral metastases. Additional tests, including pathology examination and conventional epidermal growth factor receptor (EGFR) gene mutation analysis (single-strand conformation polymorphism assay), could not identify the primary origin of the tumors, so the patient was diagnosed with CUP. After empirical chemotherapy for CUP, an NGS-based multiplex assay performed using a resected specimen of thyroid tumor detected the EGFR mutation c.2573 T > G p.Leu858Arg (L858R). Her treatment was changed to erlotinib, an EGFR tyrosine-kinase inhibiter, which dramatically shrank the tumors and decreased her serum carcinoembryonic antigen level. She achieved long-term disease control and survived for 2 years and 9 months from the first diagnosis. Conclusion This case might support the strategy that NGS-based multiplex assays could identify actionable molecular targets for individual patients with CUP.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 104-104
Author(s):  
Chunhong Hu ◽  
Lishu Zhao ◽  
Fang Wu

104 Background: With the development of next-generation sequencing (NGS) and precision medicine, targeted therapy especially molecule-driven therapy irrespective of tumor site may play an important role in cancer patients with druggable targets. Cancer of unknown primary (CUP) especially mediastinal CUP (MCUP) has poor prognosis with empirical chemotherapy but may harbor targetable genetic alterations. In the study, we evaluate the response to ALK inhibitors in ALK-positive MCUP. Methods: We queried the cancer database of the Second Xiangya hospitalfrom 2018.10 to 2019.12 for patients with ALK-positive cancers regardless of tumor site.Then we selected ALK-positive MCUP patients treated with ALK inhibitors, on which both NGS and programmed death-ligand 1 (PD-L1) testing were performed. Results: Forty-eightpatients with ALK-positive cancers were registered in the database. Two MCUP patients were found and showed different response. The first MCUP patient obtaining remarkable response to alectinib harbored ALK/TP53 co-mutation and TERT wild type accompanied by low PD-L1 expression, while the second one showing stable disease with crizotinib carried ALK/TP53/TERT co-mutation and high PD-L1 expression. Conclusions: We reveal for the first time that ALK inhibitors are applied to MCUP as first-line therapy and alectinib is firstly reported to treat MCUP patients. ALK inhibitor alectinib is expected to improve outcomes of patients with ALK-positive MCUP. NGS and PD-L1 testing should be recommended for MCUP to get more information about therapy and efficacy. [Table: see text]


2019 ◽  
Vol 37 (7) ◽  
pp. 570-579 ◽  
Author(s):  
Hidetoshi Hayashi ◽  
Takayasu Kurata ◽  
Yuichi Takiguchi ◽  
Makoto Arai ◽  
Koji Takeda ◽  
...  

PURPOSE Although gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer of unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared with empirical chemotherapy. We therefore performed a randomized study to assess whether such site-specific therapy improves outcome compared with empirical chemotherapy in previously untreated patients with CUP. PATIENTS AND METHODS Comprehensive gene expression profiling was performed by microarray analysis, and an established algorithm was applied to predict tumor origin. Patients with CUP were randomly assigned (1:1) to receive standard site-specific therapy or empirical paclitaxel and carboplatin (PC). The primary end point was 1-year survival rate. RESULTS One hundred thirty patients were randomly assigned and had sufficient biopsy tissue for molecular analysis. Efficacy analysis was performed for 50 and 51 patients in the site-specific therapy and empirical PC arms, respectively. Cancer types most commonly predicted were pancreatic (21%), gastric (21%), and lymphoma (20%). The 1-year survival rate was 44.0% and 54.9% for site-specific treatment and empirical PC ( P = .264), respectively. Median overall and progression-free survival were 9.8 and 5.1 months, respectively, for site-specific treatment versus 12.5 and 4.8 months for empirical PC ( P = .896 and .550, respectively). Median overall survival (16.7 v 10.6 months; P = .116) and progression-free survival (5.5 v 3.9 months; P = .018) were better for predicted more-responsive than less-responsive tumor types. CONCLUSION Site-specific treatment that was based on microarray profiling did not result in a significant improvement in 1-year survival compared with empirical PC, although prediction of the original site seemed to be of prognostic value.


2013 ◽  
Vol 62 (6) ◽  
pp. 922-925 ◽  
Author(s):  
Jae Won Yun ◽  
Kyung Sun Park ◽  
Chang-Seok Ki ◽  
Nam Yong Lee

Lindnera (Pichia) fabianii (Candida fabianii teleomorph) is a yeast species that is an uncommon cause of invasive human infections. This report describes what we believe to be the first human case of a catheter-related L. fabianii bloodstream infection in a neutropenic patient. The Clinical and Laboratory Standards Institute guidelines do not offer antifungal breakpoints in this neutropenic case and empirical chemotherapy was considered. Sharing our experience, we will discuss the choice of an effective antifungal agent in this uncommon clinical situation.


2011 ◽  
Vol 17 (3) ◽  
pp. 358-362 ◽  
Author(s):  
Fuminori Sakai ◽  
Yuriko Hirao ◽  
Keisuke Sunakawa ◽  
Hideaki Hanaki ◽  
Yurika Ikeda-Dantsuji ◽  
...  

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