共查询到20条相似文献，搜索用时 31 毫秒
1.
Background
Although olaparib, the first poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor approved, has been used in routine clinical practice for over three years, little has been published on its uptake, utilization patterns, and clinical outcomes.Objective
To examine real-world use and outcomes of olaparib treatment in Swedish patients during the first three years following regulatory approval.Patients and Methods
This is a population-based cohort study using data from the Swedish national registers. All individuals initiating olaparib treatment from regulatory approval to 31 December 2017 were included. The extent of off-label use was assessed based on recorded diagnoses. Ovarian cancer patients were followed until death or the end of the study period. Starting dose and dose adjustments were assessed. Time to olaparib discontinuation and overall survival were plotted using Kaplan–Meier survival curves.Results
We identified 109 patients to whom olaparib was dispensed in Sweden during the study period. Nine of these were prescribed olaparib off-label for either breast or prostate cancer and were excluded from further analyses. Median age among the remaining 100 patients with ovarian cancer was 59 years (range: 42–83). Almost all patients (96%) started on the recommended dose (400 mg [eight capsules] taken twice daily). Dose reductions were explicitly recorded for 14% of patients. Median time to discontinuation was 289 days (95% confidence interval [CI]: 226; 338). Median overall survival from olaparib initiation was 1002 days (95% CI: 676; not calculable).Conclusions
To our knowledge, this is the first population-based study of olaparib real-world use and outcomes. During the first three years following regulatory approval, olaparib was mainly prescribed to ovarian cancer patients. Ovarian cancer patients stayed on olaparib for a median of 9.5 months and the treatment appeared to be well tolerated.2.
Purpose of Review
The purpose of the review is to summarize the data regarding PD-L1 expression in breast cancer and the results of first clinical trials with PD-1 or PD-L1 inhibitors in patients with metastatic breast cancer.Recent Findings
PD-L1 expression is heterogeneous across primary breast cancers, and is generally associated with the presence of tumor-infiltrating lymphocytes and the presence of poor-prognosis features such as high grade, and aggressive molecular subtypes (triple-negative (TN), basal, HER2-enriched). Early phase clinical trials using PD-1 or PD-L1 inhibitors alone or in combination have shown objective tumor responses and durable long-term disease control, in heavily pre-treated patients, notably in the TN subtype.Summary
Blockade of PD-1 or PD-L1 shows impressive antitumor activity in some subsets of breast cancer patients. Many clinical trials are ongoing in the metastatic and neoadjuvant setting, alone and in combination with chemotherapy, targeted therapy, radiotherapy, and/or other immune therapy. The identification of biomarkers predictive for a clinical benefit is warranted.3.
M. I. Martínez-Fernández J. L. Pérez Gracia I. Gil-Bazo R. Martínez-Monge 《Clinical & translational oncology》2016,18(7):743-747
Purpose
To investigate whether bone metastases-directed stereotactic body radiation therapy (SBRT) delays the emergence of castration resistance in patients with oligometastatic prostate cancer (OPC).Methods and material
OPC is usually managed with androgen deprivation therapy (ADT). Migration to castration-resistant prostate cancer will inevitably occur in the majority of these patients. There are several strategies aimed to delay the emergence of castration resistance including intermittent ADT, second generation antiandrogens (abiraterone, enzalutamide) or metastases-directed SBRT. The present report describes two cases of patients with OPC that received SBRT 24 Gy/3Rx to the solitary bony lesion after ADT failure.Results
Both cases showed complete and durable biochemical response for 13 and 17 months, respectively.Conclusions
SBRT can be used to delay the emergence of castration resistance and the need for systemic therapy when used after ADT failure.4.
Purpose of review
This review summarizes current immunotherapies in breast cancer, with an emphasis on immune checkpoint inhibitors and vaccines.Recent findings
Combination immunotherapy with checkpoint inhibitors and cytotoxic therapies have shown promising results. Active clinical trials are ongoing in both early stage and metastatic settings for triple negative, HER2+, and hormone-positive breast cancer patients.Summary
Ongoing challenges remain in defining biomarkers that predict response to immunotherapy, determining the optimal combination immunotherapies, and enhancing the immunogenicity of breast cancer subtypes.5.
Purpose of Review
Breast cancer treatment continues to evolve as targeted therapeutic strategies are developed for the various molecular subtypes of breast cancer. The PARP inhibitors represent a novel targeted therapy for tumors with defective homologous recombination DNA repair. These agents may become standard new treatment options for patients harboring BRCA1/2 mutations and show promise in BRCA1/2 wild-type patients with triple-negative breast cancers, which are treated predominantly with traditional cytotoxic chemotherapy. This review will discuss the results of clinical trials of these agents in breast cancer as well as important ongoing and anticipated trials.Recent Findings
Recent reports support the use of olaparib monotherapy in BRCA1/2-mutated metastatic cancer. Results of PARP inhibitor combinations with chemotherapy have been mixed. The addition of veliparib failed to improve pathological complete response rates in patients with early-stage triple-negative breast cancer treated with carboplatin (AUC6) and paclitaxel followed by doxorubicin plus cyclophosphamide in a phase 3 trial. The PARP inhibitors talazoparib and olaparib are currently being tested in the neoadjuvant and adjuvant settings but impact on survival measures will likely take years prior to reporting in these early-stage breast cancer studies.Summary
While data from the first phase 3 trials of PARP inhibitors in breast cancers are encouraging in patients with germline deleterious BRCA1/2 mutations, continued work is needed to elucidate their utility beyond the BRCA1/2-mutated population as has been possible in ovarian cancer. Additionally, defining the ideal population and setting for combination treatment remains a challenge and has been limited by synergistic toxicities.6.
Background
The introduction of immune checkpoint inhibitors (ICI) has led to rapid changes in the treatment of metastatic non-small cell lung cancer (NSCLC) without treatable driver mutations over the last few years.Objective
A brief historical outline of treatment before and a summary of changes after the arrival of ICI is given.Material and methods
A selective Pubmed search was performed employing the keywords NSCLC stage IV, checkpoint inhibitors and chemotherapy.Conclusion
The ICIs were initially introduced as second line treatment of metastatic NSCLC as several large phase III trials were able to show a clinically significant improvement compared to the standard docetaxel treatment. Meanwhile, pembrolizumab is the standard first-line treatment of NSCLC with high PD-L1 expression (TPS?>?50%). Recently, several phase III trials could show superior efficacy of the combination of an ICI with standard platinum-based doublet chemotherapy compared to chemotherapy alone. Some of the investigated combinations have already been approved for nonsquamous NSCLC and further approvals can be expected. Since the introduction of ICI long-term survival of 3 or more years has been achieved in some patients with metastatic NSCLC.7.
Purpose of Review
The diagnosis of pancreatic cancer carries with it a high mortality rate. Despite advances in the field, this has remained relatively unchanged over the last few decades. Current options for the treatment of resectable pancreatic ductal adenocarcinoma will be reviewed here in conjunction with the historical data that support them. We will focus on updates in treatment guidelines and ongoing clinical trials of interest.Recent Findings
For localized disease, standard of care includes resection followed by adjuvant chemotherapy ± chemoradiation. Recently, a report was published supporting the use of doublet therapy with gemcitabine and capecitabine (as opposed to gemcitabine monotherapy), which prompted a practice-changing update to major treatment guidelines. Multiple trials using neoadjuvant treatment, novel therapies, and different forms of radiation are ongoing.Summary
Although pancreatic cancer is an active area of research, outcomes remain dismal. Clinical trials will need to be more robust and innovative to drastically improve survival statistics.8.
Purpose
Men who are survivors of prostate cancer report a variety of psychological and physical factors contributing to a lower quality of life, and physical activity can assist to mitigate these issues. This review aims to provide a summary of physical activity behaviour change trials targeting prostate cancer survivors, assess the feasibility of these interventions and, if possible, identify intervention and study characteristics associated with significant intervention effects.Method
Four databases (PubMed, CINAHL, PsycINFO and EMBASE) were systematically searched for randomised controlled trials containing at least one behavioural outcome relating to physical activity published up until July 2016. Forward and backwards, hand, key author citation searching and known research were also considered.Results
From a total of 13, 828 titles, the search resulted in 12 studies (6 prostate cancer only and 6 mixed cancer interventions), eight of which found positive results most often related immediately to post-intervention aerobic activity. Factors relating to efficacy were not conclusive due to the heterogeneity of studies and lack of cancer-specific data in mixed cancer trials. Future research focusing on intervention reach, maintenance of intervention effects and resistance training outcomes is needed.Conclusion
There is preliminary evidence to suggest that a variety of physical activity behaviour change interventions targeting men with a history of prostate cancer can be efficacious, at least in the short term. Experimental studies are required to identify key intervention features.Implications for Cancer Survivors
Physical activity interventions can assist prostate cancer survivors in relation to short-term lifestyle change, though more evidence is required to improve the clarity of factors related to efficacy.9.
Rihito Aizawa Kenji Takayama Kiyonao Nakamura Takahiro Inoue Takashi Kobayashi Shusuke Akamatsu Toshinari Yamasaki Osamu Ogawa Takashi Mizowaki 《International journal of clinical oncology / Japan Society of Clinical Oncology》2018,23(4):749-756
Background
Although definitive external-beam radiotherapy (EBRT) is one of the treatment options for non-metastatic castration-resistant prostate cancer (NM-CRPC), there are limited data on the long-term outcomes of this treatment.Methods
We retrospectively evaluated 31 NM-CRPC patients consecutively treated with definitive EBRT. The median age was 74 years upon EBRT initiation. The initial T stage distribution was as follows: T1c in 3, T2 in 11, T3 in 14, and T4 in 3 cases, respectively. The median prostate dose was 70.4 Gy. A castration-resistant status was defined as continuously increasing serum prostate-specific antigen levels despite ongoing hormonal therapy (HT).Results
The median follow-up duration after EBRT was 66.6 months. The median period of primary HT was 18.0 months. The 5- and 8-year overall survival rates were 74.6 and 49.8%, respectively. The 5- and 8-year prostate cancer-specific survival rates were 77.4 and 51.7%, respectively. Fourteen patients died, and prostate cancer was the cause of death in 12 of these patients. The 5- and 8-year relapse-free survival rates were 32.3 and 25.8%, respectively. Among 23 patients who experienced biochemical or clinical failure, the median duration to recurrence after EBRT was 19.3 months. The 5- and 8-year clinical failure-free survival rates were 56.0 and 51.4%, respectively. Among the 14 patients who experienced clinical failure, the median duration after EBRT was 16.0 months. The local relapse-free rates at 5 and 8 years were 91.0 and 91.0%, respectively. Grade 3 or higher adverse events were observed in four patients.Conclusion
Definitive EBRT achieved a long-term disease-free and clinical failure-free status in approximately one-third of and half of the treated NM-CRPC patients, respectively. This approach was also associated with favorable local relapse-free rates and overall survival outcomes. Definitive EBRT is a promising approach for NM-CRPC patients.10.
Joycelyn Jie Xin Lee Su Pin Choo Clarinda Chua 《Current colorectal cancer reports》2018,14(6):192-198
Purpose of Review
Although current guidelines suggest only testing for RAS and BRAF mutations as well as MMR deficiency in metastatic colon cancer, there are many other promising therapeutic targets that are being studied. We aim to review the recent literature and evidence behind some of these novel targets.Recent Findings
Many of these targets such as NTRK, ROS, ALK, and HER2 are being studied in current clinical trials and hold great potential in changing the treatment landscape for metastatic colorectal cancer.Summary
Current molecular testing algorithms may need to be expanded to allow better target discovery and for patients to benefit from more therapeutic options.11.
J. Clayton Allen Austin Kirschner Kristen R. Scarpato Alicia K. Morgans 《Current oncology reports》2017,19(2):8
Purpose of Review
We review current management strategies for patients with relapsed and refractory germ cell tumors (GCTs), defined as relapsed or persistent disease following at least one line of cisplatin-based chemotherapy. Additionally, we discuss future directions in the management of these patients.Recent Findings
Recent studies involving targeted therapies have been disappointing. Nevertheless, studies of the management of refractory germ cell cancer are ongoing, with a focus on optimal utilization of high-dose chemotherapy and autologous stem cell transplant, as well as the role of immune checkpoint inhibitors in refractory germ cell tumors. Studies aiming to identify those patients who may benefit from more intensive treatment up front to prevent the development of refractory disease are also in progress.Summary
Testicular germ cell tumors are among the most curable of all solid tumor malignancies, with cure being possible even in the refractory, metastatic setting. Treatment of refractory disease remains a challenging clinical scenario, but potentially practice changing studies are ongoing.12.
James J. Lee 《Current colorectal cancer reports》2018,14(6):175-183
Purpose of Review
There is a significant difference in embryological origin, gene expression, gene mutation profile, and microbiome between the right-sided and left-sided colon. It has been shown that the sidedness of primary colorectal cancer is a significant prognostic factor and predictive to the clinical benefit of anti-epidermal growth factor receptor (EGFR) antibody-containing chemotherapy in patients with metastatic CRC. Herein, current clinical recommendations for the treatment of patients with left-sided RAS wild-type mCRC are reviewed.Recent Findings
Retrospective analyses of prior randomized trials (CRYSTAL, PRIME, FIRE-3, CALGB 80405, and PEAK trials) showed that primary tumor sidedness is predictive to anti-EGFR antibody therapy in the first-line treatment of patients with RAS wild-type mCRC, and patients with left-sided RAS wild-type mCRC had a significantly better survival benefit with anti-EGFR antibody plus chemotherapy when compared with anti-VEGF treatment plus chemotherapy.Summary
The primary tumor sidedness is a significant prognostic factor and predictive to anti-EGFR antibody-containing chemotherapy in patients with metastatic CRC. Based on the currently available data, chemotherapy plus anti-EGFR antibody is recommended for the first-line treatment of patients with left-sided RAS wild-type mCRC. Chemotherapy plus bevacizumab or anti-EGFR antibody is recommended for the second-line therapy of RAS wild-type mCRC regardless of sidedness. However, these recommendations are based on the limited data from the retrospective analyses of prior trials, warranting further prospective randomized trials.13.
Nicholas Calvert Jiansha Wu Sophie Sneddon Jennifer Woodhouse Richard Carey-Smith David Wood Evan Ingley 《Clinical sarcoma research》2018,8(1):4
Background
Soft tissue and bone sarcoma represent a broad spectrum of different pathology and genetic variance. Current chemotherapy regimens are derived from randomised trials and represent empirical treatment. Chemosensitivity testing and whole exome sequencing (WES) may offer personalized chemotherapy treatment based on genetic mutations.Methods
A pilot, prospective, non-randomised control experimental study was conducted. Twelve patients with metastatic bone or soft tissue sarcoma that had failed first line chemotherapy treatment were enrolled for this study. Human tissue taken at surgical biopsy under general anaesthetic was divided between two arms of the trial. Subsections of the tumour were used for WES and the remainder was implanted subcutaneously in immunodeficient mice (PDX). Results of WES were analysed using a bioinformatics pipeline to identify mutations conferring susceptibility to kinase inhibitors and common chemotherapeutic agents. PDX models exhibiting successful growth underwent WES of the tumour and subsequent chemosensitivity testing.Results
WES was successful in all 12 patients, with successful establishment PDX tumours models in seven patients. WES identified potential actionable therapeutics in all patients. Significant variation in predicted therapeutics was demonstrated between three PDX samples and their matched tumour samples.Conclusion
Analysis of WES of fresh tumour specimens via a bioinformatics pipeline may identify potential actionable chemotherapy agents. Further research into this field may lead to the development of personalized cancer therapy for sarcoma.14.
Purpose of Review
Residual disease after neoadjuvant chemotherapy is a poor prognostic factor; however, proven strategies to reduce recurrence risk and improve overall survival in this patient population are limited. Previous studies of residual disease have illustrated the importance of tumor intrinsic subtypes in treatment response and mechanisms of resistance. This review summarizes the rationale for various therapeutic approaches as well as completed and ongoing clinical trials for this high-risk group of patients.Recent Findings
Regimens utilizing additional chemotherapy and targeted therapies (such as PARP inhibitors or bisphosphonates) have met with limited efficacy. Notably, a recently published randomized study of capecitabine in patients with residual disease demonstrated an improvement in disease-free survival and overall survival.Summary
While the results for capecitabine are promising, particularly for patients with triple-negative disease, the generalizability of these findings is an open question. Meanwhile, ongoing trials with novel agents that target specific tumor subtypes and the biology of residual disease may improve outcomes for other patient populations.15.
Wei Chen Ping Li Yi Liu Yu Yang Xueting Ye Fangyi Zhang Hang Huang 《Journal of experimental & clinical cancer research : CR》2018,37(1):309
Background
Prostate cancer is one of the most commonly diagnosed cancers in men worldwide. Currently available therapies for metastatic prostate cancer are only marginally effective. Therefore, new therapeutic agents are urgently needed to improve patient outcome. Isoalantolactone (IATL), an active sesquiterpene naturally present in many vegetables and medicinal plants, is known to induce cell death and apoptosis in various cancer cell lines. Nevertheless, antitumor mechanisms initiated by IATL in cancer cells have not been fully defined.Methods
Cell apoptosis and cellular ROS levels were analyzed by flow cytometry. Western blot and qRT-PCR were used to analyze the protein and mRNA levels of indicated molecules, respectively. Nude mice xenograft model was used to test the effects of IATL on prostate cancer cell growth in vivo.Results
In this study, we found that IATL dose-dependently inhibited cancer cell growth and induced apoptosis in PC-3 and DU145 cells. Mechanistically, our data found that IATL induced reactive oxygen species (ROS) production, resulting in the activation of endoplasmic reticulum stress pathway and eventually cell apoptosis in prostate cancer cells. IATL also decreased the protein expression levels of p-STAT3 and STAT3, and the effects of IATL were reversed by pretreatment with N-acetyl-L-cysteine (NAC). In vivo, we found that IATL inhibited the growth of prostate cancer xenografts without exhibiting toxicity. Treatment of mice bearing human prostate cancer xenografts with IATL was also associated with induction of ER stress and inhibtion of STAT3.Conclusion
In summary, our results unveil a previously unrecognized mechanism underlying the biological activity of IATL, and provide a novel anti-cancer candidate for the treatment of prostate cancer.16.
Purpose of Review
Current systemic management of MCRC should include periods of intensive and less intensive treatment or even complete stop. Different systemic post-induction strategies have been evaluated in many trials. The aim of this article is to review the available data on maintenance strategies in MCRC and potential options to personalize choice of the respective strategy.Recent Findings
Despite the large variability of clinical trials conducted in this setting, it can be concluded that intermittent chemotherapy does not seem to be inferior to continuous chemotherapy if at least 3 months of intensive induction treatment is applied, and active maintenance seem to be superior to complete stop after at least 3 months of induction treatment in terms of PFS and may add some benefit in terms of OS. The choice of the respective maintenance strategy may be personalized taking into account disease and patient characteristic, choice of induction treatment and response, treatment tolerability and quality of life.Summary
Patients with metastatic colorectal cancer and no options of secondary resection or local ablation should be considered for a personalized maintenance approach.17.
Purpose
Biliary tract cancers (BTC) remain one of the poorest groups of malignancies in terms of long-term survival, with only limited success in improvements by the use of systemic chemotherapy and our current repertoire of molecularly targeted therapies. Treatments that aim to adapt the patient’s own immune system to target cancer cell have shown tremendous promise in treating solid tumors such as melanoma and non-small cell lung cancer, and there are many recently completed and ongoing studies looking to move immunotherapy into the treatment of BTC. We review here both preclinical and early clinical studies of immune therapies for BTC, including autologous cell transfer, vaccinations, and immunomodulatory approaches (e.g., immune checkpoint inhibitors).Methods
Published abstracts and articles from peer-reviewed journals as well as ongoing trial information were obtained from PubMed, Google Scholar, and Clinicaltrials.gov.Results
The use of immune-mediated or immunomodulatory therapies in BTC are supported by observations that many chronic inflammatory states are associated with their development. Although success in treating BTC by the active manipulation of the immune system has been limited to date, we note many recent and ongoing areas of preclinical and clinical investigation that may translate to further clinical trials.Conclusions
As we continue to follow subgroup analyses and results from specific studies that include BTC patients, we will hopefully be able to combine these with focused preclinical investigations providing further rationale for future trial success in treating BTC.18.
19.
Elisa M. Murray Mathew A. Cherian Cynthia X. Ma Ron Bose 《Current breast cancer reports》2018,10(2):41-47
Purpose of Review
HER2 activating mutations are a new, druggable mutation identified by next-generation DNA sequencing (NGS) of breast cancer. Here, we review the recent data on the diagnosis and treatment of HER2 mutated, metastatic breast cancer.Recent Findings
Pre-clinical studies have shown that HER2 activating mutations accelerate tumor growth and can be inhibited by HER2 targeted drugs, including trastuzumab and the second-generation, pan-HER tyrosine kinase inhibitor, neratinib. HER2 mutations can be diagnosed by NGS testing on either a tumor biopsy or circulating tumor DNA obtained from peripheral blood. Case reports provided initial evidence that HER2 targeted therapies can effectively treat patients with HER2 mutated, metastatic breast cancer. Two phase II clinical trials, MutHER and SUMMIT, both demonstrate that neratinib monotherapy has clinical efficacy for these patients, with clinical benefit rate of 31–40%.Summary
HER2 targeted therapies are effective for HER2 mutated breast cancer but emergence of drug resistance remains a problem. Clinical trials are now testing neratinib-containing drug combination regimens for HER2 mutated, metastatic breast cancer patients.20.
Saira Khan Jianwen Cai Matthew E. Nielsen Melissa A. Troester James L. Mohler Laura Farnan Bettina F. Drake Andrew F. Olshan Jeannette T. Bensen 《Cancer causes & control : CCC》2018,29(11):1143-1150