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1.
Steffen?D?rfel Claus-Christoph?Steffens Dirk?Meyer Hans?Tesch Lisa?Kruggel Melanie?Frank Martina?J?nicke Norbert?Marschner The TMK-Group 《Breast cancer (Tokyo, Japan)》2018,25(3):275-283
Background
Several regimens for which efficacy was established in randomized controlled trials are recommended in current treatment guidelines for early breast cancer. However, knowledge on use and effectiveness of commonly administered chemotherapeutic agents in real-life care and across all breast cancer subtypes is limited.Methods
The prospective, multicentre German TMK cohort study (Tumour Registry Breast Cancer) recruited patients in 148 oncology outpatient-centres. Data from 1650 patients who completed adjuvant chemotherapy were analysed regarding treatment regimens and taxane use from 2007 to 2014. The association of patient characteristics with application of taxane-free regimens was examined with a multivariate regression model.Results
The preferred adjuvant treatment shifted from fluorouracil, anthracycline and cyclophosphamide containing regimens to anthracycline/taxane combinations. Taxane use increased for all subtypes, and the greatest rise was among node-negative patients. Older age, node-negativity, lower grading, HR-positive/HER2-negative subtype and earlier start year of therapy were significantly associated with taxane-free therapy.Conclusions
Treatment with anthracycline/taxane-based chemotherapy in Germany has been rising for every subtype. The increased taxane use reflects updated guideline recommendations over the past decade. Cohort studies like the TMK provide insight into real-life treatment of patients outside of clinical trials.2.
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.3.
Yusuke Okuma Yukio Hosomi Kageaki Watanabe Satoshi Takahashi Tatsuru Okamura Tsunekazu Hishima 《International journal of clinical oncology / Japan Society of Clinical Oncology》2016,21(3):531-538
Background
The key drugs for chemotherapy of thymic carcinoma are gradually being revealed in phase II and conventional retrospective studies. Gemcitabine is regarded as one of these key drugs according to the findings of clinical trials in which it was combined with capecitabine. However, the activity of single-agent gemcitabine concerning refractory thymic carcinoma remains unclear.Patients and methods
We conducted a retrospective review of the medical records of refractory thymic carcinoma patients previously treated with platinum-containing chemotherapy between 1980 and 2014.Results
Of all 11 patients in this study, the objective response rate regarding gemcitabine was 36.4 % [95 % confidence interval (CI) 15.2–64.6] using the RECIST criteria and the response criteria proposed by the ITMIG. The median progression-free survival time was 4.3 months (95 % CI 0.7–11.0). The survival time from the start of gemcitabine treatment was 28.5 months (95 % CI 5.5–47.8), and from the start of first-line chemotherapy was 46.5 months (95 % CI 7.3–47.8).Conclusions
Gemcitabine achieved a moderate response and has the potential to be used as a key drug for thymic carcinoma. Some patients treated with gemcitabine demonstrated prolonged cancer control even in later lines of chemotherapy.4.
Xiu-Wei Zhang Yu-Xiang Ma Yang Sun Yu-Bo Cao Qin Li Chong-An Xu 《Targeted oncology》2017,12(3):309-321
Background
It remains controversial whether the addition of a second cytotoxic agent can further improve the therapeutic effect of gemcitabine monotherapy in advanced or metastatic pancreatic cancer (LA/MPC).Objective
The objective of the present systematic review and meta-analysis was to investigate the efficacy and safety of gemcitabine-based doublet chemotherapy regimens compared to single-agent gemcitabine in the first-line treatment of unresectable LA/MPC.Methods
We searched for randomized controlled trials (RCTs) of gemcitabine monotherapy versus gemcitabine in combination with a second cytotoxic agent in patients with LA/MPC. The last search date was December 31, 2016.Results
Twenty-seven RCTs were identified and included in the present systematic review and meta-analysis, involving a total of 7343 patients. The meta-analysis showed that gemcitabine-based combination therapy significantly improved overall survival (OS) (HR: 0.89; 95% confidence interval (CI): 0.85-0.94; P?<?0.0001), progression-free survival (PFS) (HR: 0.80; 95% CI: 0.73-0.88; P?<?0.0001), and overall response rate (ORR) (RR: 1.83; 95% CI: 1.62-2.07; P?<?0.0001) in comparison to single-agent gemcitabine. Subgroup analysis suggested that the antitumor activity differed between gemcitabine-based combination regimens: doublet regimens of gemcitabine plus a taxoid, and gemcitabine plus a fluoropyrimidine, in particular an oral fluoropyrimidine, resulted in a significant OS benefit for the patients. However, the combination of gemcitabine with other cytotoxic agents, such as platinum compounds or topoisomerase inhibitors failed to reduce the mortality risk. Combination therapy caused more grade 3/4 toxicities, including neutropenia, thrombocytopenia, vomiting, diarrhea, and fatigue.Conclusions
Gemcitabine-based doublet regimens demonstrated superiority over gemcitabine monotherapy in overall efficacy, but were associated with increased toxicity. Different gemcitabine-based combinations showed different antitumor activity, and doublet regimens of gemcitabine in combination with a taxoid or a fluoropyrimidine, in particular an oral fluoropyrimidine provided significant survival benefits in the first-line treatment of unresectable LA/MPC.5.
Jordi Ginés Eliazar Sabater Clara Martorell María Grau Marta Monroy Miguel A. Casado 《Clinical & translational oncology》2011,13(7):485-498
Objectives
To evaluate the magnitude of benefit obtained by taxanes as adjuvant treatment of breast cancer and to assess the best method for their administration.Material and methods
We performed a systematic search of phase III randomised clinical trials that included patients with non-metastatic breast cancer in whom comparisons were chemotherapy (CT) containing a taxane (docetaxel or paclitaxel) vs. CT without taxanes (first-generation trials), or CT with taxane in both treatment arms (second-generation trials), administered after surgery. The parameters of efficacy evaluated were disease-free survival (DFS) and overall survival (OS). The data obtained in the first-generation trials (number of relapses and deaths) were submitted to a meta-analysis. The odds ratio (OR) combined with DerSimonian and Laird (OR DL) and 95% confidence interval (95%CI) were calculated. Further, an analysis was performed of those trials that included only patients with nodal involvement (N+). In both cases, the results were also analysed as a function of the taxane used, and with indirect comparisons between the two. The second-generation trials were analysed to assess the optimum method of administration.Results
A total of 17 trials were selected for the metaanalysis (30,672 patients). The OR DL was 0.82 (95%CI: 0.76=2–0.88) for DFS and 0.83 (95%CI: 0.75–0.91) for OS. In N+ patients the results were 0.80 (95%CI: 0.74–0.86) and 0.79 (95%CI: 0.69–0.89), respectively. Docetaxel and paclitaxel significantly increased the DFS and OS. In our indirect comparison, the benefit of docetaxel on OS was significantly superior to that obtained with paclitaxel in N+ patients (OR: 0.79; 95%CI: 0.63–0.98).Conclusions
The administration of adjuvant CT-based taxanes reduces the risk of relapse and death. This reduction is superior in clinical trials that included only N+ patients. With the available evidence, it would appear that the best method of administering paclitaxel is weekly and for docetaxel tri-weekly.6.
Po-Ju Lin Luke J. Peppone Michelle C. Janelsins Supriya G. Mohile Charles S. Kamen Ian R. Kleckner Chunkit Fung Matthew Asare Calvin L. Cole Eva Culakova Karen M. Mustian 《Current oncology reports》2018,20(1):5
Purpose of Review
To (1) explain what yoga is, (2) summarize published literature on the efficacy of yoga for managing cancer treatment-related toxicities, (3) provide clinical recommendations on the use of yoga for oncology professionals, and (4) suggest promising areas for future research.Recent Findings
Based on a total of 24 phase II and one phase III clinical trials, low-intensity forms of yoga, specifically gentle hatha and restorative, are feasible, safe, and effective for treating sleep disruption, cancer-related fatigue, cognitive impairment, psychosocial distress, and musculoskeletal symptoms in cancer patients receiving chemotherapy and radiation and cancer survivors.Summary
Clinicians should consider prescribing yoga for their patients suffering with these toxicities by referring them to qualified yoga professionals. More definitive phase III clinical trials are needed to confirm these findings and to investigate other types, doses, and delivery modes of yoga for treating cancer-related toxicities in patients and survivors.7.
Background
The aim of this study was to evaluate the pharmacological costs of conversion chemotherapy with targeted biological agents in an unselected population of advanced colorectal cancer (CRC) patients in order to achieve an R0 liver resection.Methods
Full reports and updates of randomized clinical trials (RCTs) that compared at least two front-line therapy regimens with targeted biological agents for advanced CRC patients were selected. The present evaluation was restricted to randomized phase II and III trials. The costs of drugs are at the Pharmacy Hospital and are expressed in euros (€).Results
Our study began with the evaluation of 683 abstracts. Forty-eight trials were considered appropriate for further analysis. A more in-depth evaluation looking for the trials reporting the liver resection rates following conversion chemotherapy brought to the exclusion of other 37 trials, leaving 11 randomized trials (three phase II trials, including 522 patients and eight phase III trials, including 7191 patients). The pharmacological costs of conversion therapy increased with the substitution of prolonged infusion 5-Fluorouracil by capecitabine and, to a much higher extent, with the introduction of biologicals.Conclusions
Two key issues are presented in this review. First, the pharmacological costs of commonly used front line regimens based on the targeted biological agents for the treatment of advanced CRC are highly variable. Second, the performance of the published schemes, in terms of resection rates, depends on patient’s selection, tumor characteristics, and on the type of the scheme.8.
Purpose
Sarcomas are a rare and heterogeneous variant of cancer. The standard of care treatment involves surgical resection with radiation in high-risk patients. Despite appropriate treatment approximately 50 % of patients will suffer and die from recurrent disease. The purpose of this article is to review the current evidence concerning the use of neoadjuvant chemotherapy with or without radiation in soft tissue sarcomas.Methods
An in-depth literature search was conducted using Ovid Medline and PubMed.Results
The most active chemotherapeutic agents in sarcoma are anthracyclines and ifosfamide. Adjuvant chemotherapy trials show only minimal benefit. Neoadjuvant chemotherapy offers the potential advantage of reducing the extent of surgery, increasing the limb salvage rate, early exposure of micrometastatic disease to chemotherapy, and assessment of tumor response to chemotherapy. Some retrospective and phase II trials suggest a benefit to neoadjuvant chemotherapy. Unfortunately, no clearly positive phase III prospectively randomized trials exist for neoadjuvant therapy in soft tissue sarcomas.Conclusions
The current neoadjuvant chemotherapy trials that do exist are heterogeneous resulting in conflicting results. However, neoadjuvant chemotherapy with or without radiation can be considered in patients with high-risk disease in an attempt to improve long-term outcomes.9.
10.
Lorenzo?Fornaro Caterina?Vivaldi Stefano?Cereda Francesco?Leone Giuseppe?Aprile Sara?Lonardi Nicola?Silvestris Daniele?Santini Michele?Milella Chiara?Caparello Gianna?Musettini Giulia?Pasquini Alfredo?Falcone Giovanni?Brandi Isabella?Sperduti Enrico?Vasile
Background
After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far.Methods
We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings.Results
A total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months).Conclusions
The current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management.11.
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.12.
Purpose of Review
Advanced urothelial carcinoma (aUC) has long been treated preferably with cisplatin-based chemotherapy, but many patients are cisplatin-ineligible whereas for those who progress on a platinum-based regimen treatment options are limited. We review key recent data regarding immune checkpoint inhibitors that are changing this treatment landscape.Recent Findings
Since May 2016, five different agents targeting the PD-1/PD-L1 pathway (atezolizumab, pembrolizumab, nivolumab, avelumab, durvalumab) have received FDA approval for the treatment of aUC in the platinum-refractory setting, while pembrolizumab and atezolizumab are FDA-approved for cisplatin-ineligible patients in the first-line setting. Clinical outcomes and safety profiles of these agents appear relatively comparable across separate trials; however, only pembrolizumab is supported by level I evidence from a large randomized phase III trial showing overall survival benefit over conventional cytotoxic salvage chemotherapy in the platinum-refractory setting.Summary
Pembrolizumab has the highest level of evidence in platinum-refractory aUC, whereas pembrolizumab and atezolizumab have comparable level of evidence in the frontline setting in cisplatin-ineligible patients. Ongoing research is evaluating novel agents, various rational combinations, and sequences, as well as predictive and prognostic biomarkers.13.
Purpose of Review
We aim to summarise the available evidence on systemic therapies for advanced anal cancer.Recent Findings
There is no universal consensus on the management of this condition and the prognosis remains poor. Nevertheless, significant progress has been recently made including completion of the first, ever-conducted, randomised trial in the first-line setting, investigation of immunotherapy in the refractory setting and use of comprehensive genomic profiling for a better molecular characterisation of this disease and the identification of novel potential targets.Summary
The combination of a platinum agent and a fluoropyrimidine is generally considered the standard first-line treatment. Other cytotoxic agents, especially docetaxel and paclitaxel, have shown activity in both the chemotherapy-naive and chemo-refractory setting and are currently being investigated in clinical trials. Finally, further to the promising results of early clinical trials, immunotherapy with checkpoint inhibitors (i.e. nivolumab and pembrolizumab) is likely to become a standard second-line treatment option.14.
Michael T. Serzan Benjamin A. Weinberg Mohamed E. Salem 《Current colorectal cancer reports》2017,13(6):411-418
Purpose of Review
We review second-line biological therapies for metastatic colorectal cancer (mCRC), including their mechanisms of action, adverse events, survival outcomes, optimal chemotherapy combinations, and sequencing of agents.Recent Findings
The advent of biological therapeutics targeting vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways has enhanced the benefits afforded by the plethora of chemotherapeutic agents for patients with mCRC over the past 10 years, nearly tripling the median OS. Individual biomarkers predicting prognosis and response to VEGF vs. EGFR therapy have been identified. For patients who progress on first-line VEGF therapy, evidence suggests that continued VEGF inhibition may be as efficacious as changing to EGFR therapy with less adverse effects. However, for patients who progress after first-line EGFR therapy, early studies suggest changing to agents targeting the VEGF pathway.Summary
Biological options for patients with mCRC who progressed on first-line concomitant chemotherapy and biologic therapy depend on individual tumor characteristics and choice of first-line therapy. Future research should focus on prognostic and predictive biomarkers to better inform choice of first-line and sequential therapy beyond progression.15.
Purpose of Review
In the last decade, there have been multiple landmark therapeutic advances for the treatment of metastatic prostate cancer, both in the castration-resistant and hormone-sensitive setting. In this review, we highlight recent progress and ongoing trials for metastatic prostate cancer, including advances in chemotherapy, androgen receptor-directed therapy, targeted therapies, and immunotherapy.Recent Findings
Several landmark studies for men with metastatic hormone-sensitive prostate cancer demonstrated improvement in overall survival with the addition of docetaxel chemotherapy or abiraterone acetate to standard androgen deprivation therapy. A single-arm phase 2 study of the PARP inhibitor olaparib demonstrated high response rates and more favorable progression-free and overall survival for men with metastatic castration-resistant prostate cancer and DNA repair defects treated with olaparib compared with men without DNA repair defects. Multiple ongoing clinical trials are investigating novel hormonal therapies and combinations of chemotherapy, targeted small molecules, immunotherapy, and radiopharmaceuticals.Summary
Progress continues to be made in the treatment of metastatic prostate cancer, and ongoing clinical trials continue to investigate novel agents and approaches to treatment.16.
Purpose of Review
Chronic lymphocytic leukemia (CLL) has multiple current frontline therapy options, including chemoimmunotherapy (CIT) and most recently, ibrutinib. Here, we review the most recent updates in the frontline treatment of CLL, including updates in CIT, updates in targeted therapies, and ongoing clinical trials.Recent Findings
Ibrutinib was FDA-approved for the upfront treatment of CLL in 2016 after being studied in older patients and those with 17p deletions or TP53 mutations. The introduction of ibrutinib has dramatically changed the treatment paradigm of CLL.Summary
Recent updates in CIT include that immunoglobulin heavy chain variable (IGHV) gene mutation status is strongly predictive of response to CIT. Regarding targeted therapy, next-generation BTK and PI3K inhibitors are currently being studied in the upfront treatment of CLL, which may have less toxicity than their first-generation counterparts. Other novel targeted therapies are being studied in the frontline setting, most notably venetoclax including in combinations, with hopes to achieve chemotherapy-free, time-limited treatment options. Multiple key ongoing phase 3 clinical trials will be answering these important clinical questions.17.
Background
Primary malignant sarcomas in children, adolescents and young adults are rare and represent a major challenge for the treating physician.Aim
The aim of this article is to provide a comprehensive overview on sarcomas in children, adolescents and young adults. This article provides an overview of the epidemiology, clinical presentation, diagnoses, tumor biology, international therapy strategies and currently active phase I, II and III clinical trials.Material and methods
The article is based on a selective literature search and also provides data from the authors’ own national and international clinical trials.Results
The treatment must follow a multimodal concept, which ultimately requires close cooperation between many disciplines. As a result of modern interdisciplinary treatment approaches consisting of chemotherapy, surgery and/or radiotherapy, two thirds of patients can be cured if they undergo early and appropriate therapy. This requires a precise and early diagnosis and treatment in selected medical centers with an interdisciplinary team of specialized oncologists, surgeons and radiotherapists is highly recommended.18.
Sarah J. Stephens Christopher G. Willett Manisha Palta Brian G. Czito 《Current colorectal cancer reports》2018,14(6):199-206
Purpose of Review
This review summarizes the relevant literature on the use of total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer. It highlights the most notable literature published and briefly discusses future directions.Recent Findings
Recent randomized trials evaluating TNT show improved rates of pathologic complete response and patient treatment tolerance with this approach.Summary
The rationale for TNT includes the poor patient tolerance of adjuvant chemotherapy and the persistent risk of distant disease in patients with locally advanced rectal cancer, despite improvements in local control. Randomized trials have focused on short-term pathologic endpoints. Ongoing phase 3 trials are evaluating long-term disease-related outcomes, allowing for a more thorough evaluation of this treatment paradigm. TNT may also facilitate organ preservation in appropriately selected patients.19.
N. Kentepozidis P. Economopoulou Ch. Christofyllakis L. Chelis A. Polyzos N. Vardakis F. Koinis L. Vamvakas P. Katsaounis K. Kalbakis Ch. Nikolaou V. Georgoulias A. Kotsakis 《Clinical & translational oncology》2017,19(3):317-325
Background
Platinum-based chemotherapy is the standard front-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, non-platinum combinations of third-generation chemotherapeutic agents are considered an alternative therapeutic option for patients who cannot tolerate the toxic effects of platinum compounds. In this study, the efficacy and toxicity of the combination of irinotecan plus cisplatin (IC) was compared to pemetrexed plus cisplatin (PC) regimen, in platinum-naïve patients with advanced NSCLC, who had been previously treated with the combination of a taxane plus gemcitabine.Patients and methods
A total of 124 patients with locally advanced or metastatic NSCLC were randomly assigned to either irinotecan 110 mg/m2 on day 1 and 100 mg/m2 on day 8 plus cisplatin 80 mg/m2 on day 8 every 3 weeks (IC arm) or pemetrexed 500 mg/m2 plus cisplatin 80 mg/m2 on day 1 every 3 weeks (PC arm). The primary endpoint of the study was the overall response rate (ORR).Results
The ORR and median progression-free survival (PFS) in the IC arm were 18 % and 3.3 months, respectively, while in the PC arm were 19 % and 4.2 months (p = ns). Median overall survival (OS) was significantly higher in patients with PC (6.9 vs. 10.9; p = 0.013). PC regimen had a better toxicity profile compared to IC, with a statistically significant lower incidence of grade 3/4 neutropenia (3 vs. 31 %; p = 0.0001) and diarrhea (1.6 vs. 14.7 %, p = 0.018).Conclusions
In patients with advanced NSCLC pretreated with docetaxel/gemcitabine, the combination of pemetrexed/cisplatin is associated with increased OS and is better tolerated than the combination of irinotecan/cisplatin and should be considered as a valid therapeutic option for platinum-naive, previously treated patients.ClinicalTrials.gov Identifier
NCT00614965.20.