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International Journal of Surgery... Feb 2019Gastric cancer, as one of the increasingly common malignancies, has experienced high morbidity throughout many countries at present. Currently, chemotherapy regimen with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastric cancer, as one of the increasingly common malignancies, has experienced high morbidity throughout many countries at present. Currently, chemotherapy regimen with more efficacy and safety for advanced gastric cancer (AGC) is needed. We aimed to assess the clinical efficacy and safety of S-1 combined with paclitaxel (PTX) for AGC by performing a systematic review and meta-analysis of the published studies.
METHOD
All published randomized controlled trials (RCTs) of S-1 combined with PTX for AGC were searched. Studies that included patients with locally advanced or metastases' gastric cancers were included. We searched the databases included Cochrane Library of Clinical Comparative Trials, MEDLINE, Embase, American Society of Clinical Oncology meeting abstracts and China National Knowledge Internet (CNKI) from 2000 to 2018. We searched the database up to January 2018. The first endpoint was overall survival (OS). Other endpoints were progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Safety analyses were also performed.
RESULTS
A total of 7 trials (including 1407 patients, 711 patients in intervention group and 696 patients in control group) were included in the present analysis. S-1 combined with PTX significantly improved the OS [HR = 0.78, 95% CI: 0.60-0.97, P = 0.000],PFS [HR = 0.70, 95% CI: 0.55-0.85, P = 0.000], ORR [RR = 1.30, 95%CI: 1.05-1.60, P = 0.017] and DCR [RR = 1.15, 95%CI: 1.04-1.27, P = 0.008] of patients with AGC. The grade 3 or 4 haematological and non-hematologic toxicities were anemia [RR = 1.71, 95% CI: 1.04-2.79, P = 0.03], neutropenia [RR = 1.65, 95% CI: 1.32-2.06, P < 0.0001] and anorexia [RR = 1.66, 95% CI: 1.05-2.64, P = 0.03] respectively.
CONCLUSION
S-1 combined with PTX may be a good choice for patients with AGC. S-1 plus PTX experienced more efficacy and safety when compared with S-1 alone or S-1 plus other drugs.
Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Hematologic Diseases; Humans; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Analysis; Tegafur
PubMed: 30641155
DOI: 10.1016/j.ijsu.2018.11.010 -
Health Technology Assessment... May 2007To assess the clinical effectiveness and cost-effectiveness of gemcitabine, used in combination with paclitaxel, as a second-line treatment for people with metastatic... (Review)
Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of gemcitabine, used in combination with paclitaxel, as a second-line treatment for people with metastatic breast cancer who have relapsed following treatment with anthracycline-based chemotherapy.
DATA SOURCES
Electronic databases were searched from inception to March 2006. Clinical advisers were also consulted.
REVIEW METHODS
A systematic review of the literature was undertaken to appraise the clinical and cost-effectiveness of gemcitabine. A Markov state transition model was developed for the economic evaluation.
RESULTS
The systematic review identified only one randomised controlled trials (RCT), and this has not yet been fully published. The methodological quality and quality of reporting of the included trial were assessed to be poor using standard criteria, but this may be due to the lack of information in the limited publications rather than being a fair reflection of the trial's quality. This RCT compared gemcitabine and paclitaxel therapy with paclitaxel monotherapy in 529 patients with metastatic breast cancer who had previously received anthracyclines, but no prior chemotherapy for metastatic breast cancer. Approximately 71% of the gemcitabine/paclitaxel patients survived for 1 year, compared with 61% of the paclitaxel group. The hazard ratio showed a 26% lower chance of survival in the paclitaxel group, and time to progressive disease was also shorter in this group. The overall response rate was higher in the gemcitabine/paclitaxel group than in the paclitaxel group. Adverse events, particularly neutropenia, were more common with gemcitabine/paclitaxel combination therapy than with paclitaxel therapy alone. The economic model was run for a simulation of 1000 patients, assuming that chemotherapy continued until patients' disease progressed. This base-case analysis found an incremental cost-effectiveness ratio (ICER) of 58,876 pounds per quality-adjusted life-year (QALY) gained and 30,117 pounds per life-year gained. The model was re-run with treatment restricted to a maximum of six cycles per patient, reflecting normal practice. This yielded an ICER of 38,699 pounds per QALY gained and 20,021 pounds per life-year gained.
CONCLUSIONS
The review of clinical effectiveness is based on data from a single RCT that has not yet been fully published. While only tentative conclusions can be drawn from this, the evidence may indicate that treatment with gemcitabine and paclitaxel confers an improved outcome for patients in terms of survival and disease progression, but at the cost of increased toxicity. An economic model developed for this review reflects high costs per QALY for this treatment combination. The base-case analysis shows high ICERs, with costs per QALY gained close to 60,000 pounds. Adopting a more realistic treatment protocol, with chemotherapy limited to a maximum of six cycles, gives a more favourable cost-effectiveness estimate. However, this was still higher than would usually be considered to be a cost-effective treatment from the NHS's perspective. Future research recommendations include an update of this review in 12-18 months' time, by which time the included RCT should be fully published. It would also be useful to compare gemcitabine with currently used treatments for metastatic breast cancer, including capecitabine and vinorelbine.
Topics: Age Factors; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cost-Benefit Analysis; Deoxycytidine; Female; Humans; Markov Chains; Models, Economic; Neoplasm Metastasis; Neoplasm Recurrence, Local; Paclitaxel; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Factors; Gemcitabine
PubMed: 17462169
DOI: 10.3310/hta11190 -
JACC. Cardiovascular Interventions Jun 2016This study sought to perform a systematic review and network meta-analysis to compare the relative safety and efficacy of contemporary DES and BVS. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study sought to perform a systematic review and network meta-analysis to compare the relative safety and efficacy of contemporary DES and BVS.
BACKGROUND
To improve outcomes of patients undergoing percutaneous coronary revascularization, there have been advances in the design of drug-eluting stents (DES), including the development of drug-eluting bioresorbable vascular scaffolds (BVS).
METHODS
Prospective, randomized, controlled trials comparing bare-metal stents (BMS), paclitaxel-eluting stents (PES), sirolimus-eluting stents (SES), Endeavor zotarolimus-eluting stents (E-ZES), cobalt-chromium (CoCr) everolimus-eluting stents (EES), platinum-chromium (PtCr)-EES, biodegradable polymer (BP)-EES, Resolute zotarolimus-eluting stents (R-ZES), BP biolimus-eluting stents (BP-BES), hybrid sirolimus-eluting stents (H [Orsiro]-SES), polymer-free sirolimus- and probucol-eluting stents, or BVS were searched in online databases. The primary endpoint was definite or probable stent thrombosis at 1 year.
RESULTS
A total of 147 trials including 126,526 patients were analyzed in this study. All contemporary DES were superior to BMS and PES in terms of definite or probable stent thrombosis at 1 year. CoCr-EES, PtCr-EES, and H-SES were associated with significantly lower risk than BVS. CoCr-EES and H-SES were superior to SES and BP-BES. The risk of myocardial infarction was significantly lower with H-SES than with BVS. There were no significant differences regarding all-cause or cardiac mortality. Contemporary devices including BVS showed comparably low risks of repeat revascularization.
CONCLUSIONS
Contemporary DES, including biocompatible DP-DES, BP-DES, and polymer-free DES, showed a low risk of definite or probable stent thrombosis at 1 year. BVS had an increased risk of device thrombosis compared with CoCr-EES, PtCr-EES, and H-SES. Data from extended follow-up are warranted to confirm the long-term safety of contemporary coronary devices.
Topics: Absorbable Implants; Bayes Theorem; Coronary Disease; Coronary Thrombosis; Drug-Eluting Stents; Humans; Markov Chains; Monte Carlo Method; Network Meta-Analysis; Odds Ratio; Percutaneous Coronary Intervention; Prosthesis Design; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 27262860
DOI: 10.1016/j.jcin.2016.03.038 -
Clinical and Translational Science Oct 2022Taxane-based chemotherapy regimens are used as first-line treatment for breast cancer. Neurotoxicity, mainly taxane-induced peripheral neuropathy (TIPN), remains the... (Meta-Analysis)
Meta-Analysis
Taxane-based chemotherapy regimens are used as first-line treatment for breast cancer. Neurotoxicity, mainly taxane-induced peripheral neuropathy (TIPN), remains the most important dose-limiting adverse event. Multiple genes may be associated with TIPN; however, the strength and direction of the association remain unclear. For this reason, we systematically reviewed observational studies of TIPN pharmacogenetic markers in breast cancer treatment. We conducted a systematic search of terms alluding to breast cancer, genetic markers, taxanes, and neurotoxicity in Ovid, ProQuest, PubMed, Scopus, Virtual Health, and Web of Science. We assessed the quality of evidence and bias profile. We extracted relevant variables and effect measures. Whenever possible, we performed random-effects gene meta-analyses and examined interstudy heterogeneity with meta-regression models and subgroup analyses. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and STrengthening the REporting of Genetic Association Studies (STREGA) reporting guidance. A total of 42 studies with 19,431 participants were included. These evaluated 262 single-nucleotide polymorphisms (SNPs) across 121 genes. We conducted meta-analyses on 23 genes with 60 SNPs (19 studies and 6246 participants). Thirteen individual SNPs (ABCB1-rs2032582, ABCB1-rs3213619, BCL6/-rs1903216, /CAND1-rs17781082, CYP1B1-rs1056836, CYP2C8-rs10509681, CYP2C8-rs11572080, EPHA5-rs7349683, EPHA6-rs301927, FZD3-rs7001034, GSTP1-rs1138272, TUBB2A-rs9501929, and XKR4-rs4737264) and the overall SNPs' effect in four genes (CYP3A4, EphA5, GSTP1, and SLCO1B1) were statistically significantly associated with TIPN through meta-analysis. In conclusion, through systematic review and meta-analysis, we found that polymorphisms, and particularly 13 SNPs, are associated with TIPN, suggesting that genetics does play a role in interindividual predisposition. Further studies could potentially use these findings to develop individual risk profiles and guide decision making.
Topics: Female; Humans; Breast Neoplasms; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP3A; Genetic Markers; Liver-Specific Organic Anion Transporter 1; Neurotoxicity Syndromes; Paclitaxel; Peripheral Nervous System Diseases; Pharmacogenetics; Polymorphism, Single Nucleotide; Taxoids
PubMed: 35892315
DOI: 10.1111/cts.13370 -
The Cochrane Database of Systematic... Jul 2022Ovarian cancer is the seventh most frequent cancer diagnosis worldwide, and the eighth leading cause of cancer mortality. Epithelial ovarian cancer is the most common... (Review)
Review
BACKGROUND
Ovarian cancer is the seventh most frequent cancer diagnosis worldwide, and the eighth leading cause of cancer mortality. Epithelial ovarian cancer is the most common kind, accounting for 90% of cases. First-line therapy for women with epithelial ovarian cancer consists of a combination of cytoreductive surgery and platinum and taxane-based chemotherapy. However, more than 50% of women with epithelial ovarian cancer will experience a relapse and require further chemotherapy and at some point develop resistance to platinum-based drugs. Currently, guidance on the use of most chemotherapy drugs, including taxanes, is unclear for women whose epithelial ovarian cancer has recurred. Paclitaxel, topotecan, pegylated liposomal doxorubicin hydrochloride, trabectedin and gemcitabine are all licensed for use in the UK at the discretion of clinicians, following discussion with the women as to potential adverse effects. Taxanes can be given in once-weekly regimens (at a lower dose) or three-weekly regimens (at a higher dose), which may have differences in the severity of side effects and effectiveness. As relapsed disease suggests incurable disease, it is all the more important to consider side effects and the impact of treatment schedules, as well as quality of life, and not only the life-prolonging effects of treatment.
OBJECTIVES
To assess the efficacy and toxicity of different taxane monotherapy regimens for women with recurrent epithelial ovarian, tubal or primary peritoneal cancer.
SEARCH METHODS
We searched CENTRAL, MEDLINE and Embase, up to 22 March 2022. Other related databases and trial registries were searched as well as grey literature and no additional studies were identified. A total of 1500 records were identified.
SELECTION CRITERIA
We included randomised controlled trials of taxane monotherapy for adult women diagnosed with recurrent epithelial ovarian, tubal or primary peritoneal cancer, previously treated with platinum-based chemotherapy. We included trials comparing two or more taxane monotherapy regimens. Participants could be experiencing their first recurrence of disease or any line of recurrence.
DATA COLLECTION AND ANALYSIS
Two review authors screened, independently assessed studies, and extracted data from the included studies. The clinical outcomes we examined were overall survival, response rate, progression-free survival, neurotoxicity, neutropenia, alopecia, and quality of life. We performed statistical analyses using fixed-effect and random-effects models following standard Cochrane methodology. We rated the certainty of evidence according to the GRADE approach.
MAIN RESULTS
Our literature search yielded 1500 records of 1466 studies; no additional studies were identified by searching grey literature or handsearching. We uploaded the search results into Covidence. After the exclusion of 92 duplicates, we screened titles and abstracts of 1374 records. Of these, we identified 24 studies for full-text screening. We included four parallel-group randomised controlled trials (RCTs). All trials were multicentred and conducted in a hospital setting. The studies included 981 eligible participants with recurrent epithelial ovarian cancer, tubal or primary peritoneal cancer with a median age ranging between 56 to 62 years of age. All participants had a WHO (World Health Organization) performance status of between 0 to 2. The proportion of participants with serous histology ranged between 56% to 85%. Participants included women who had platinum-sensitive (71%) and platinum-resistant (29%) relapse. Some participants were taxane pre-treated (5.6%), whilst the majority were taxane-naive (94.4%). No studies were classified as having a high risk of bias for any of the domains in the Cochrane risk of bias tool. We found that there may be little or no difference in overall survival (OS) between weekly paclitaxel and three-weekly paclitaxel, but the evidence is very uncertain (risk ratio (RR) of 0.94, 95% confidence interval (CI) 0.66 to 1.33, two studies, 263 participants, very low-certainty evidence). Similarly, there may be little or no difference in response rate (RR of 1.07, 95% CI 0.78 to 1.48, two studies, 263 participants, very low-certainty evidence) and progression-free survival (PFS) (RR of 0.83, 95% CI 0.46 to 1.52, two studies, 263 participants, very low-certainty evidence) between weekly and three-weekly paclitaxel, but the evidence is very uncertain. We found differences in the chemotherapy-associated adverse events between the weekly and three-weekly paclitaxel regimens. The weekly paclitaxel regimen may result in a reduction in neutropenia (RR 0.51, 95% 0.27 to 0.95, two studies, 260 participants, low-certainty evidence) and alopecia (RR 0.58, 95% CI 0.46 to 0.73, one study, 205 participants, low-certainty evidence). There may be little or no difference in neurotoxicity, but the evidence was very low-certainty and we cannot exclude an effect (RR 0.53, 95% CI 0.19 to 1.45, two studies, 260 participants). When examining the effect of paclitaxel dosage in the three-weekly regimen, the 250 mg/m paclitaxel regimen probably causes more neurotoxicity compared to the 175 mg/m regimen (RR 0.41, 95% CI 0.21 to 0.80, one study, 330 participants, moderate-certainty evidence). Quality-of-life data were not extractable from any of the included studies.
AUTHORS' CONCLUSIONS
Fewer people may experience neutropenia when given weekly rather than three-weekly paclitaxel (low-certainty evidence), although it may make little or no difference to the risk of developing neurotoxicity (very low-certainty evidence). This is based on the participants receiving lower doses of drug more often. However, our confidence in this result is low and the true effect may be substantially different from the estimate of the effect. Weekly paclitaxel probably reduces the risk of alopecia, although the rates in both arms were high (46% versus 79%) (low-certainty evidence). A change to weekly from three-weekly chemotherapy could be considered to reduce the likelihood of toxicity, as it may have little or no negative impact on response rate (very low-certainty evidence), PFS (very low-certainty evidence) or OS (very low-certainty evidence). Three-weekly paclitaxel, given at a dose of 175 mg/m compared to a higher dose,probably reduces the risk of neurotoxicity.We are moderately confident in this result; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. A change to 175 mg/m paclitaxel (from a higher dose), if a three-weekly regimen is used, probably has little or no negative impact on PFS or OS (very low-certainty evidence).
Topics: Adult; Alopecia; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Ovarian Neoplasms; Paclitaxel; Taxoids
PubMed: 35866378
DOI: 10.1002/14651858.CD008766.pub3 -
European Review For Medical and... Mar 2020We reviewed studies comparing survival outcomes such as overall survival (OS), progression free survival (PFS), and toxicity profile between patients treated with... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of pegylated liposomal doxorubicin and paclitaxel plus carboplatin-based chemotherapy as first line treatment for patients with ovarian cancer: a systematic review and meta-analysis of randomized controlled trials.
We reviewed studies comparing survival outcomes such as overall survival (OS), progression free survival (PFS), and toxicity profile between patients treated with Pegylated Liposomal Doxorubicin (PLD) combination and those treated with paclitaxel combination for ovarian cancer. We conducted systematic searches in various databases including Medline, Cochrane Controlled Register of Trials (CENTRAL), ScienceDirect, and Google Scholar from inception until August 2019. We used the Cochrane risk of bias tool to assess the quality of published trials. We carried out a meta-analysis with random-effects model and reported pooled Hazard ratios (HR) or Risk ratios (RR) with 95% confidence intervals (CIs). In total, we analysed 7 studies including 3,676 participants. All the studies were randomized controlled trials, while majority of studies had low bias risks. We did not find significant evidence for any of these outcomes except progression free survival (favoured PLD combination therapy pooled HR=0.87; 95% CI: 0.77-0.98). Worst grade toxicities like allergy (pooled RR: 1.86; 95% CI: 1.06-3.24) and neurotoxicity (pooled RR: 5.59; 95% CI: 1.43-21.84) were significantly higher among patients receiving paclitaxel combination therapy when compared to patients receiving PLD combination therapy. To summarize, PLD combination therapy is non-inferior to paclitaxel combination therapy in the management of ovarian cancer with respect to survival outcomes and worst grade toxicity profile. However, clinical recommendations cannot be made, as the evidence is not conclusive or significant enough.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Disease-Free Survival; Doxorubicin; Female; Humans; Ovarian Neoplasms; Paclitaxel; Polyethylene Glycols; Randomized Controlled Trials as Topic
PubMed: 32271409
DOI: 10.26355/eurrev_202003_20655 -
Therapeutic Advances in Cardiovascular... Jun 2015The clinical efficacy and safety of drug-coated balloon (DCB) angioplasty in patients with coronary in-stent restenosis (ISR) has been demonstrated. The objective of... (Review)
Review
OBJECTIVES
The clinical efficacy and safety of drug-coated balloon (DCB) angioplasty in patients with coronary in-stent restenosis (ISR) has been demonstrated. The objective of this article is to provide comparative cost efficacy data for DCB angioplasty in various countries based on the original methodology of the Medical Technologies Evaluation Programme (MTEP) at the National Institute for Health and Clinical Excellence (NICE) in 2010.
STUDY DESIGN
Published and unpublished Health Technology Assessment (HTA) reports were evaluated for comparison in selected countries. Furthermore, a systematic review of economic evaluations of DCB angioplasty versus standard treatments (uncoated balloon angioplasty or drug-eluting stent implantations) was conducted.
METHODS
National cost efficacy data were evaluated using Markov state transition models which were adapted to fit each country's device and procedure related costs. The clinical input for adverse events was defined with two relevant trials for in-stent restenosis of bare metal stents (BMS-ISR) and of drug-eluting stents (DES-ISR).
RESULTS
In the UK, Germany, Switzerland, South Africa, Japan and Brazil, DCB angioplasty is cost-effective when compared with drug-eluting stents to treat either BMS-ISR or DES-ISR.
CONCLUSIONS
DCB angioplasty ought to be the preferred treatment option for patients with BMS-ISR and DES-ISR from the payers' point of view.
Topics: Angioplasty, Balloon, Coronary; Coated Materials, Biocompatible; Coronary Restenosis; Cost Savings; Cost-Benefit Analysis; Global Health; Humans; Paclitaxel; Practice Guidelines as Topic; Tubulin Modulators
PubMed: 25731186
DOI: 10.1177/1753944715574655 -
Cancers Apr 2019The tumor microenvironment plays an important role in the initiation and progression of pancreatic adenocarcinoma (PDAC). In this systematic review, we provide an... (Review)
Review
The tumor microenvironment plays an important role in the initiation and progression of pancreatic adenocarcinoma (PDAC). In this systematic review, we provide an overview of clinical trials with stroma-targeting agents. We systematically searched MEDLINE/PubMed and the EMBASE database, using the PRISMA guidelines, for eligible clinical trials. In total, 2330 records were screened, from which we have included 106 articles. A meta-analysis could be performed on 51 articles which describe the targeting of the vascular endothelial growth factor (VEGF) pathway, and three articles which describe the targeting of hyaluronic acid. Anti-VEGF therapies did not show an increase in median overall survival (OS) with combined hazard ratios (HRs) of 1.01 (95% confidence interval (CI) 0.90-1.13). Treatment with hyaluronidase PEGPH20 showed promising results, but, thus far, only in combination with gemcitabine and nab-paclitaxel in selected patients with hyaluronic acid (HA) tumors: An increase in median progression free survival (PFS) of 2.9 months, as well as a HR of 0.51 (95% CI 0.26-1.00). In conclusion, we found that anti-angiogenic therapies did not show an increased benefit in median OS or PFS in contrast to promising results with anti-hyaluronic acid treatment in combination with gemcitabine and nab-paclitaxel. The PEGPH20 clinical trials used patient selection to determine eligibility based on tumor biology, which underlines the importance to personalize treatment for pancreatic cancer patients.
PubMed: 31035512
DOI: 10.3390/cancers11050588 -
Therapeutic Advances in Medical Oncology 2022The role of bevacizumab combined with paclitaxel and carboplatin in the first-line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC) has been...
Efficacy and safety of adding bevacizumab biosimilar or original drug to platinum-based chemotherapy as first-line treatment in patients with advanced NSCLC: a systematic review and meta-analysis.
INTRODUCTION
The role of bevacizumab combined with paclitaxel and carboplatin in the first-line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC) has been supported by a large number of data. However, whether bevacizumab biosimilars have the same efficacy and safety as the original drug is still controversial. This meta-analysis was designed to evaluate whether bevacizumab biosimilars have the same clinical efficacy and safety as the original drug in patients with advanced non-squamous NSCLC.
METHODS
Electronic databases (PubMed, Embase, Cochrane, CNKI, Wanfang, and VIP) and the ClinicalTrail.gov website were extensively searched using relevant search criteria. We included phase III randomized controlled trials (RCTs) to compare the efficacy and safety of marketed biosimilars and Avastin in the first-line treatment of patients with advanced NSCLC. The risk of bias of the included studies was assessed using the RoB 2 assessment scale, and the RevMan 5.4 statistical software was used for meta-analysis.
RESULTS
A total of 6360 patients were included in 11 RCTs. There was no statistical difference between the experimental group and the control group in terms of effectiveness [objective response rate (at week 18), disease control rate (at week 18), median duration of response, median progression-free survival, median overall survival (OS), and OS after 12 months]. In terms of safety [treatment-emergent adverse events (grade ⩾3) and treatment-related adverse events (grade ⩾3)], there was also no significant difference between biosimilars and Avastin.
CONCLUSIONS
The efficacy and safety of bevacizumab biosimilars in the treatment of advanced non-squamous NSCLC are highly similar to those of the original drug combined with paclitaxel and carboplatin, respectively.
PubMed: 36312816
DOI: 10.1177/17588359221130501 -
International Journal of Radiation... Feb 2013Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis.
METHODS AND MATERIALS
After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade ≥2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups.
RESULTS
The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving ≥20 Gy (V(20)) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P<.001), with a trend for age (OR 1.24 per decade, P=.09); the model remained predictive in the validation set with good discrimination in both datasets (c-statistic >0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V(20), and lower-lobe tumor location.
CONCLUSIONS
Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Asia; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Decision Trees; Etoposide; Europe; Female; Humans; Logistic Models; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; North America; Paclitaxel; Radiation Pneumonitis; Radiotherapy Dosage
PubMed: 22682812
DOI: 10.1016/j.ijrobp.2012.04.043