-
Frontiers in Oncology 2023The best choice of first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. We aimed to compare the effectiveness and safety determined...
BACKGROUND
The best choice of first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. We aimed to compare the effectiveness and safety determined in randomized clinical trials of doublet and triplet treatments for mHSPC.
METHODS
Medline, Embase, Cochrane Central and ClinicalTrials.gov were searched from inception through July 01, 2022. Eligible studies were phase III randomized clinical trials evaluating androgen deprivation treatment (ADT) alone, doublet therapies [ADT combined with docetaxel (DOC), novel hormonal agents (NHAs), or radiotherapy (RT)], or triplet therapies (NHA+DOC+ADT) as first-line treatments for mHSPC. Outcomes of interest included overall survival (OS), progression-free survival (PFS) and grades 3-5 adverse events (AEs). Subgroup analyses were performed based on tumor burden. The effects of competing treatments were assessed by Bayesian network meta-analysis using R software.
RESULTS
Ten trials with 12,298 patients comparing nine treatments were included. Darolutamide (DARO) +DOC+ADT ranked best in terms of OS benefits (OR 0·52 [95% CI 0·39-0·70]), but its advantages were all statistically insignificant compared with other therapy options except for DOC+ADT (OR 0·68 [95% CI 0·53-0·88]) and RT+ADT (OR 0·57 [95% CI 0·40-0·80]). In terms of PFS, enzalutamide(ENZA)+DOC+ADT (OR 0·32 [95% CI 0·24-0·44]) and abiraterone and prednisone (AAP) +DOC+ADT (OR 0·33 [95% CI 0·25-0·45]) ranked best. For patients with high volume disease (HVD), low volume disease (LVD), and visceral metastases, the optimal therapies were AAP+DOC+ADT (OR 0·52 [95% CI 0·33-0·83]), apalutamide+ADT (OR 0·52 [95% CI 0·26-1·05]) and DARO+DOC+ADT (OR 0·42 [95% CI 0·13-1·34]), respectively. For safety, AAP+DOC+ADT (OR 3·56 [95% CI 1·51-8·43]) ranked worst with the highest risk of grade 3-5 AEs.
CONCLUSIONS
Triple therapies may further improve OS and PFS but may be associated with a decrease in safety. Triplet therapies could be suggested for HVD patients, while doublet combinations should still be preferred for LVD patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPEROFILES/303117_STRATEGY_20220202.pdf, identifier CRD4202303117.
PubMed: 36959793
DOI: 10.3389/fonc.2023.1104242 -
Cancers Sep 2022Several new drugs and combination strategies can be used to treat patients with recurrent or metastatic head and neck squamous cell carcinoma in the second-line... (Review)
Review
Comparison of Second-Line Treatments for Patients with Platinum-Resistant Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Systematic Review and Bayesian Network Meta-Analysis.
Several new drugs and combination strategies can be used to treat patients with recurrent or metastatic head and neck squamous cell carcinoma in the second-line treatment. Questions regarding the relative efficacy and safety of any two of the multiple second-line treatment strategies have emerged. This study aims to compare second-line treatments for patients with platinum-resistant recurrent or metastatic head and neck squamous cell carcinoma. Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched to identify relevant articles. Direct and indirect evidence in terms of the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events grade ≥ 3 (grade ≥ 3 trAE) were analyzed in this Bayesian network meta-analysis. A total of twenty-three trials involving 5039 patients were included. These studies compared 20 different treatments, including the standard of care (SOC: docetaxel, methotrexate, or cetuximab), PD-1 inhibitors (nivolumab or pembrolizumab), durvalumab, tremelimumab, durvalumab + tremelimumab, palbociclib + SOC, tivantinib + SOC, sorafenib + SOC, EMD1201081 + SOC, vandetanib + SOC, PX-866 + SOC, 5-fluorouracil + SOC, cixutumumab + SOC, gefitinib + SOC, cabazitaxel, nolatrexed, duligotuzumab, zalutumumab, gefitinib, and afatinib. Among the currently available treatment options, compared to the standard of care (SOC: docetaxel, methotrexate, or cetuximab), the PD inhibitor significantly improved OS, ORR, and grade ≥ 3 trAE. Afatinib presented a better PFS and ORR than the SOC. Compared with afatinib, the PD-1 inhibitor had a better OS but a worse PFS. In conclusion, compared to the SOC, the PD-1 inhibitor significantly improved the OS, ORR, and grade ≥ 3 trAE. Afatinib presented a better PFS and ORR than the SOC. Compared with afatinib, the PD-1 inhibitor had a better OS but a worse PFS.
PubMed: 36139631
DOI: 10.3390/cancers14184472 -
Annals of Gastroenterological Surgery Mar 2019Survival of patients with cT4 esophageal cancer is dismal. Although the optimal treatment strategy remains to be established, two treatment options are available for cT4... (Review)
Review
BACKGROUND
Survival of patients with cT4 esophageal cancer is dismal. Although the optimal treatment strategy remains to be established, two treatment options are available for cT4 esophageal cancers: definitive chemoradiation (dCRT) and induction treatment followed by conversion surgery (CS). However, little is known concerning the differences in clinical outcome between patients with T4 esophageal tumors treated with dCRT and those eventually treated with CS.
METHODS
A systematic search of the scientific literature on PubMed/MEDLINE was carried out using the keywords "T4 esophageal cancer," "invading (involving) adjacent organ," "definitive chemoradiation," "induction therapy," "salvage surgery," and "conversion surgery," obtaining 28 reports published up to July 2018.
RESULTS/CONCLUSION
We found that CS was superior to dCRT with respect to local disease control and short-term survival; however, CS was associated with relatively higher perioperative mortality and morbidity. Alternatively, although dCRT might often cause fistula formation, a clinical complete response to dCRT is likely to lead to a better prognosis. Recent advances in chemotherapeutic agents have led to triple induction chemotherapy, with docetaxel, cisplatin, and 5-fluorouracil (DCF), which has shown promise as an initial induction treatment for cT4 esophageal cancer. Indeed, this regimen could control both local and systemic disease, which enables curative resection without preoperative CRT. Moreover, some appropriate changes in perioperative management and intensive systemic chemotherapy might enhance patient outcome. Randomized controlled trials with a large sample size are needed to establish the standard treatment for cT4 esophageal cancer.
PubMed: 30923786
DOI: 10.1002/ags3.12222 -
Cancer Medicine Jul 2023Uterine leiomyosarcoma (uLMS) is an aggressive mesenchymal neoplasm associated with a poor prognosis. Systemic chemotherapy is the standard therapy for patients with... (Meta-Analysis)
Meta-Analysis Review
Uterine leiomyosarcoma (uLMS) is an aggressive mesenchymal neoplasm associated with a poor prognosis. Systemic chemotherapy is the standard therapy for patients with uLMS. However, it is unclear which treatment regimen results in the most favorable clinical outcome. We performed a meta-analysis and meta-regression analysis to assess the efficiency of different treatments received by patients with advanced, metastatic, and relapsing uLMS by evaluating the objective response rate (ORR) and disease control rate (DCR) as primary endpoints. The frequentist random effects meta-analysis model was used to compare the outcomes of different treatment regimens for advanced uLMS. A meta-regression analysis was performed to estimate the association between the study-specific hazard ratios and specific demographic variables. A meta-analysis of 51 reports including 1664 patients was conducted. Among patients who received adjuvant chemotherapy (916 patients; 55%), gemcitabine and docetaxel were the most frequently used drugs. First-line monotherapy with alkylating agents (pooled ORR = 0.48; 95% confidence interval [CI]: 0.44-0.52) and second-line monotherapy with protein kinase inhibitors (pooled ORR = 0.45; 95% CI: 0.39-0.52) resulted in favorable prognoses. The combinations of anthracycline plus alkylating therapy (pooled DCR = 0.74; 95% CI: 0.67-0.79) and of gemcitabine plus docetaxel (pooled DCR = 0.70; 95% CI: 0.63-0.75) showed the greatest benefits when used as first-line and second-line chemotherapies, respectively. Subgroup meta-analysis results revealed that dual-regimen therapies comprising anthracycline plus alkylating therapy and gemcitabine plus docetaxel are practical therapeutic choices for International Federation of Gynecology and Obstetrics stages III-IVb with distant metastases when assessed by computed tomography (p = 0.001). Furthermore, neoadjuvant chemotherapy and local radiotherapy resulted in favorable outcomes for patients with earlier stages of distant relapsed uLMS (p < 0.001). Our findings provide a basis for designing new therapeutic strategies and can potentially guide clinical practice toward better prognoses for uLMS patients with advanced, metastatic, and relapsing disease.
Topics: Female; Humans; Leiomyosarcoma; Docetaxel; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local; Gemcitabine; Uterine Neoplasms; Proportional Hazards Models; Anthracyclines
PubMed: 37081717
DOI: 10.1002/cam4.5930 -
Minerva Urologica E Nefrologica = the... Feb 2018To evaluate the available evidence on the standard diagnosis and management of men with metastatic castration resistant prostate cancer (mCRPC), and providing the timely... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
To evaluate the available evidence on the standard diagnosis and management of men with metastatic castration resistant prostate cancer (mCRPC), and providing the timely update on new pharmacological treatments.
EVIDENCE ACQUISITION
A systematic literature search from from January 2000 until March 2017 was performed by combining the following MESH terms: castrate resistant prostate cancer, abiraterone, enzalutamide, 223radium, sipuleucel-T, docetaxel, cabazitaxel, resistance mechanisms, resistance to androgen deprivation, androgen receptor (AR) mutations, amplifications, splice variants, and AR alterations. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA).
EVIDENCE SYNTHESIS
In the few last years the introduction of new treatment modalities as abiraterone or enzalutamide have significantly change our prospective in mCRPC management increasing patients survival and quality of life. The standard imaging modalities to define the presence of regional or distant metastasis or the different resistant mechanisms to the available treatments are still an issue of debate, however several studies are ongoing to define the standard of care and to reduce treatments' resistance. Data from ongoing phase III trials are awaited to introduce in clinical new effective treatments that can be used in patients resistant to abiraterone/enzalutamide or more probably in a different phase of the disease.
CONCLUSIONS
Castration resistant prostate cancer is now the key issue in prostate cancer management and research. Our challenge in the near future will be to identify the right treatment or better the right combination and sequencing of treatments that should be used in patients with mCRPC or even with advanced prostate cancer.
Topics: Humans; Male; Prostatic Neoplasms, Castration-Resistant; Quality of Life
PubMed: 28707844
DOI: 10.23736/S0393-2249.17.02976-9 -
British Journal of Cancer Feb 2009We aimed to assess the incidence of febrile neutropenia in patients with non small cell lung cancer treated with docetaxel as second line chemotherapy by systematic... (Meta-Analysis)
Meta-Analysis Review
We aimed to assess the incidence of febrile neutropenia in patients with non small cell lung cancer treated with docetaxel as second line chemotherapy by systematic review and meta-analysis of clinical studies. Published studies were retrieved and included if they considered docetaxel at the licensed dose after a previous chemotherapy regimen, and reported the proportion of patients getting FN. Meta-analysis was conducted to estimate the proportion of patients who experience one or more episodes of FN. The pooled, random effects meta-analysis estimate for the proportion of patients who experience one or more episodes of FN on docetaxel was 5.95% (95% CI 4.22-8.31) based on 13 studies, comprising 1609 patients. No significant differences were seen either between studies that permitted the use of prophylactic granulocyte colony-stimulating factors or between phase II and phase III trials.Evidence from randomised controlled trials suggests that the incidence of FN with docetaxel is around 6% and therefore an important factor to consider in the choice of the chemotherapy regimen.
Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Docetaxel; Female; Fever; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Risk Factors; Taxoids
PubMed: 19190633
DOI: 10.1038/sj.bjc.6604863 -
The Canadian Journal of Urology Apr 2014Castration resistant prostate cancer (CRPC) is the single common pathway to prostate cancer death. For men with symptomatic metastatic disease, docetaxel chemotherapy... (Review)
Review
INTRODUCTION
Castration resistant prostate cancer (CRPC) is the single common pathway to prostate cancer death. For men with symptomatic metastatic disease, docetaxel chemotherapy remains a standard of care. However, blood prostatic-specific antigen (PSA) testing allows the identification of CRPC before clinical metastases or symptoms occur, providing a long diagnostic lead time in many patients. The use of secondary hormonal manipulations (SHMs) in men not candidates for immediate chemotherapy is reviewed.
MATERIALS AND METHODS
PubMed was searched for randomized clinical trials, systematic reviews or clinical practice guidelines addressing SHMs in CRPC.
RESULTS
A recent systematic review and practice guideline was identified, and used as the evidence base for this review along with reports from randomized trials over the past year.
CONCLUSIONS
The goals of therapy with SHMs should be discussed with patients and their preferences considered. In men without clinical evidence of metastases, gonadal androgen suppression should be maintained and generally patients should be observed. There is no clear evidence that SHMs are of benefit in these patients. Abiraterone plus prednisone is of proven benefit in men with CRPC metastases who are without significant symptoms prior to chemotherapy. Based on emerging data, enzalutamide may be of similar benefit. Use of other SHMs should be based on patient preference and consideration of possible adverse effects; with the exception of low dose prednisone, there is little evidence of benefit supporting their use. For patients accepting these uncertainties, a trial of nonsteroidal antiandrogen may be considered as an adjunct to observation, followed by low dose corticosteroid with immediate or delayed addition of abiraterone (in men with metastases) as a reasonable next step.
Topics: Androgen Antagonists; Androstenes; Androstenols; Antineoplastic Agents, Hormonal; Benzamides; Drug Therapy, Combination; Humans; Male; Nitriles; Phenylthiohydantoin; Prednisone; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome
PubMed: 24775722
DOI: No ID Found -
Frontiers in Pharmacology 2023In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have...
In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have decreased. However, it has been reported that cardiovascular disease has become the second leading cause of long-term morbidity and fatality among cancer survivors. Cardiotoxicity from anticancer drugs affects the heart's function and structure and can occur during any stage of the cancer treatments, which leads to the development of cardiovascular disease. To investigate the association between anticancer drugs for non-small cell lung cancer (NSCLC) and cardiotoxicity as to whether: different classes of anticancer drugs demonstrate different cardiotoxicity potentials; different dosages of the same drug in initial treatment affect the degree of cardiotoxicity; and accumulated dosage and/or duration of treatments affect the degree of cardiotoxicity. This systematic review included studies involving patients over 18 years old with NSCLC and excluded studies in which patients' treatments involve radiotherapy only. Electronic databases and registers including Cochrane Library, National Cancer Institute (NCI) Database, PubMed, Scopus, Web of Science, ClinicalTrials.gov and the European Union Clinical Trials Register were systematically searched from the earliest available date up until November 2020. A full version protocol of this systematic review (CRD42020191760) had been published on PROSPERO. A total of 1785 records were identified using specific search terms through the databases and registers; 74 eligible studies were included for data extraction. Based on data extracted from the included studies, anticancer drugs for NSCLC that are associated with cardiovascular events include bevacizumab, carboplatin, cisplatin, crizotinib, docetaxel, erlotinib, gemcitabine and paclitaxel. Hypertension was the most reported cardiotoxicity as 30 studies documented this cardiovascular adverse event. Other reported treatment-related cardiotoxicities include arrhythmias, atrial fibrillation, bradycardia, cardiac arrest, cardiac failure, coronary artery disease, heart failure, ischemia, left ventricular dysfunction, myocardial infarction, palpitations, and tachycardia. The findings of this systematic review have provided a better understanding of the possible association between cardiotoxicities and anticancer drugs for NSCLC. Whilst variation is observed across different drug classes, the lack of information available on cardiac monitoring can result in underestimation of this association. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191760, identifier PROSPERO CRD42020191760.
PubMed: 37383708
DOI: 10.3389/fphar.2023.1137983 -
Value in Health : the Journal of the... Oct 2018To estimate the relative effectiveness of enzalutamide in chemotherapy-naive metastatic castration-resistant prostate cancer by conducting a systematic literature review... (Meta-Analysis)
Meta-Analysis Review
Systematic Review and Network Meta-Analysis of Treatments for Chemotherapy-Naive Patients with Asymptomatic/Mildly Symptomatic Metastatic Castration-Resistant Prostate Cancer.
OBJECTIVES
To estimate the relative effectiveness of enzalutamide in chemotherapy-naive metastatic castration-resistant prostate cancer by conducting a systematic literature review and a network meta-analysis (NMA).
METHODS
A systematic literature review identified randomized controlled trials comparing enzalutamide, abiraterone/prednisone, radium-223, sipuleucel-T, or docetaxel with each other or placebo in chemotherapy-naive or mixed populations (with and without prior chemotherapy) with asymptomatic/mildly symptomatic metastatic castration-resistant prostate cancer. Feasibility assessment evaluated the trials' suitability for NMA inclusion. The main outcomes were hazard ratios (HRs) for overall survival (OS) and radiographic progression-free survival (rPFS).
RESULTS
Searches of relevant bibliographic databases, trial registers, Web sites, and conference abstracts conducted in October 2014 identified 25,712 records. Ten randomized controlled trials were eligible for the NMA. Enzalutamide was superior to placebo for OS and rPFS (fixed-effects model). NMA results (fixed-effects model) showed no evidence of a difference between enzalutamide and abiraterone/prednisone (HR 0.95 [95% CrI 0.77-1.16]), sipuleucel-T (HR 1.07 [95% CrI 0.84-1.37]), or radium-223 (HR 1.10 [95% CrI 0.87-1.37]) for OS. HRs were similar for the random-effects model. Nevertheless, results (fixed-effects model) suggested that enzalutamide was superior to abiraterone/prednisone (HR 0.59 [95% CrI 0.48-0.72]) and sipuleucel-T (HR 0.32 [95% CrI 0.25-0.42]) for rPFS. Results also suggested superiority of enzalutamide versus placebo, abiraterone/prednisone, or sipuleucel-T for time to chemotherapy.
CONCLUSIONS
For rPFS, the NMA suggests that enzalutamide is superior to abiraterone/prednisone and sipuleucel-T. There is no evidence of a statistically significant difference in OS between enzalutamide and abiraterone/prednisone, sipuleucel-T, or radium-223. Given the limitations in network construction and underlying assumptions made to complete these analyses, results should be interpreted with caution.
Topics: Antineoplastic Combined Chemotherapy Protocols; Asymptomatic Diseases; Humans; Male; Prostatic Neoplasms, Castration-Resistant; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30314628
DOI: 10.1016/j.jval.2018.03.012 -
Journal of Clinical Oncology : Official... Jul 2014To provide evidence-based recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)... (Review)
Review
Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline.
PURPOSE
To provide evidence-based recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.
METHODS
The American Society of Clinical Oncology convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic literature review from January 2009 to October 2012. Outcomes of interest included overall survival, progression-free survival (PFS), and adverse events.
RESULTS
A total of 16 trials met the systematic review criteria. The CLEOPATRA trial found survival and PFS benefits for docetaxel, trastuzumab, and pertuzumab in first-line treatment, and the EMILIA trial found survival and PFS benefits for trastuzumab emtansine (T-DM1) in second-line treatment. T-DM1 also showed a third-line PFS benefit. One trial reported on duration of HER2-targeted therapy, and three others reported on endocrine therapy for patients with HER-positive advanced breast cancer.
RECOMMENDATIONS
HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and T-DM1 for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations or T-DM1 (if not previously administered) and may offer pertuzumab, if the patient has not previously received it. Optimal duration of chemotherapy is at least 4 to 6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive/progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone.
Topics: Ado-Trastuzumab Emtansine; Anastrozole; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Clinical Trials as Topic; Comorbidity; Docetaxel; Drug Administration Schedule; Evidence-Based Medicine; Female; Health Status Disparities; Healthcare Disparities; Humans; Lapatinib; Letrozole; Maytansine; Molecular Targeted Therapy; Nitriles; Quinazolines; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Societies, Medical; Taxoids; Trastuzumab; Treatment Outcome; Triazoles; United States
PubMed: 24799465
DOI: 10.1200/JCO.2013.54.0948