-
Clinical Oncology (Royal College of... Feb 2019Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome...
AIMS
Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation.
MATERIALS AND METHODS
One hundred patients were treated from June 2011 to November 2016. Treatment consisted of 55 Gy in 20 daily fractions concurrently with split-dose cisplatin vinorelbine chemotherapy over 4 weeks followed by two cycles of cisplatin vinorelbine only. Survival was estimated using Kaplan-Meier and Cox regression was carried out for known prognostic factors. A systematic search of literature was conducted using Medline, Embase and Cochrane databases and relevant references included.
RESULTS
In total, 97% of patients completed radiotherapy and 73% of patients completed all four cycles of chemotherapy. One patient died of a cardiac event during consolidative chemotherapy. There were two cases of grade 4 toxicities (one sepsis, one renal impairment). Grade 3 toxicities included nausea/vomiting (17%), oesophagitis (15%), infection with neutropenia (12%) and pneumonitis (4%). Clinical benefit was seen in 86%. Two-year progression-free survival and overall survival rates were 49% and 58%, respectively. The median progression-free survival and overall survival were 23.4 and 43.4 months, respectively. The only significant prognostic factor was the number of chemotherapy cycles received (P = 0.02). The systematic review identified 13 relevant studies; a variety of regimens were assessed with variable reporting of outcomes and toxicity but with overall an improvement in survival over time.
CONCLUSION
Our experience compared with the original phase II trial showed improved treatment completion rates and survival with acceptable morbidity. With appropriate patient selection this regimen is an effective treatment option for locally advanced non-small cell lung cancer. This study helps to benchmark efficacy and toxicity rates while considering the addition of new agents to hypofractionated concurrent chemoradiotherapy. The agreement of a standard regimen for assessment in future trials would be beneficial.
Topics: Adult; Aged; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Female; Humans; Lung Neoplasms; Male; Middle Aged; Survival Rate; Treatment Outcome
PubMed: 30415784
DOI: 10.1016/j.clon.2018.10.006 -
Expert Review of Anticancer Therapy Nov 2018Cisplatin-based chemotherapy administered concomitantly to thoracic radiotherapy is the treatment recommended by the European guidelines for fit patients with...
Cisplatin-based chemotherapy administered concomitantly to thoracic radiotherapy is the treatment recommended by the European guidelines for fit patients with unresectable stage III non-small cell lung cancer (NSCLC). Cisplatin may be combined with etoposide, vinorelbine or other vinca alkaloids, which act also as radiation sensitizers. Initially administered intravenously, vinorelbine is also available as oral formulation and is the only orally available microtubule-targeting agent. In addition, the oral formulation avoids the risk of extravasation and phlebitis. Areas covered: A literature search has been performed for articles reporting phase II-III trials aimed to evaluate efficacy and safety of oral vinorelbine-based chemoradiotherapy in unresectable locally advanced NSCLC. Expert commentary: In a series of trials with various protocols published from 2008 to 2018, mostly phase II studies, oral vinorelbine demonstrated a significant activity in concomitant chemoradiotherapy for unresectable locally advanced NSCLC typically as part of combination schedules with cisplatin. Main toxicities were hematologic (neutropenia and anemia); non-hematological toxicities included esophagitis and gastro-duodenal adverse events. Large prospective phase III trials are needed to confirm the role of vinorelbine-based chemotherapy associated to thoracic radiotherapy in unresectable stage III NSCLC and more particularly trials with metronomic oral vinorelbine.
Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Humans; Lung Neoplasms; Neoplasm Staging; Vinorelbine
PubMed: 30173589
DOI: 10.1080/14737140.2018.1518714 -
International Journal of Clinical... Feb 2018Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which accounts for 20 - 25% of cases of breast cancers, is highly aggressive. Due to... (Review)
Review
OBJECTIVE
Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which accounts for 20 - 25% of cases of breast cancers, is highly aggressive. Due to cardiotoxicity and increasing resistance associated with trastuzumab, the first-line treatment, there is a need for effective second-line therapies in treating HER2-positive breast cancer. In this context, there has been increasing interest in the combination of lapatinib plus capecitabine. The aim of this systematic review was to assess the efficacy of lapatinib plus capecitabine for HER2-positive breast cancer after progression with trastuzumab therapy, in comparison with capecitabine monotherapy and other agents such as vinorelbine and trastuzumab emtansine.
MATERIALS AND METHODS
We performed a keyword search in five electronic databases (OVID MEDLINE, the Cochrane Library, Web of Science, SCOPUS, and CINAHL; January 2010 to April 2017) for trials in patients with HER2-positive breast cancer that has progressed on trastuzumab. After screening, the relevant studies were assessed for their methodological quality (including selection bias, randomization, control for confounders, and blinding) by two reviewers independently.
RESULTS AND DISCUSSION
A total of 50 studies were identified; only 6 of those met the inclusion criteria and were analyzed. Five received a weak rating on the quality assessment tool, and none could be considered as being of high scientific quality after taking the risk of bias and other confounding variables into account. The studies demonstrated that lapatinib plus capecitabine is effective in extending median overall (OS) and progression-free survival (PFS) outcomes, achieving OS of 37.6 - 108.7 weeks and PFS of 21.1 - 30 weeks across studies. However, median OS and PFS for trastuzumab emtansine therapy were found to be considerably better (133.9 weeks and 41.6 weeks, respectively) than for lapatinib plus capecitabine.
CONCLUSION
The results suggest that the combination of lapatinib plus capecitabine can improve PFS and OS in patients with HER2-positive breast cancer that has progressed on trastuzumab. However, it appears that trastuzumab emtansine provides better treatment outcomes in this context. .
Topics: Ado-Trastuzumab Emtansine; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Capecitabine; Disease Progression; Disease-Free Survival; Female; Humans; Lapatinib; Maytansine; Neoplasm Metastasis; Quinazolines; Receptor, ErbB-2; Survival Analysis; Time Factors; Trastuzumab; Treatment Outcome
PubMed: 29231164
DOI: 10.5414/CP203123 -
World Journal of Clinical Oncology Aug 2016To evaluate the current role of sorafenib, an oral multikinase inhibitor in the treatment of breast cancer.
AIM
To evaluate the current role of sorafenib, an oral multikinase inhibitor in the treatment of breast cancer.
METHODS
An extensive search of the literature until March 2016 was carried out in Medline and clinicaltrials.gov, by using the search terms "sorafenib" and "breast cancer". Papers found were checked for further relevant publications. Overall, 21 relevant studies were found, 18 in advanced breast cancer (16 in stage IV and two in stages III-IV) and three in early breast cancer.
RESULTS
Among studies in advanced breast cancer, there were two trials with sorafenib as monotherapy, four trials of sorafenib in combination with taxanes, two in combination with capecitabine, one with gemcitabine and/or capecitabine, one with vinorelbine, one with bevacizumab, one with pemetrexed and one with ixabepilone, three trials of sorafenib in combination with endocrine therapy and two trials in women with brain metastases undergoing whole brain radiotherapy. In addition, there was one trial of sorafenib added to standard chemotherapy in the adjuvant setting, and two trials in the neoadjuvant setting. In general, sorafenib was well tolerated in breast cancer patients, though its dosage had to be adjusted in some trials, and discontinuation rates were high, particularly for the combination of sorafenib with anastrozole. Sorafenib monotherapy and combinations with taxanes, bevacizumab and ixabepilone showed inadequate efficacy, while efficacy results from combinations with gemcitabine and/or capecitabine and possibly tamoxifen were more promising.
CONCLUSION
At present, sorafenib should not be used for the treatment of breast cancer outside of clinical trials and more clinical data are needed in order to support its standard use in breast cancer therapy.
PubMed: 27579253
DOI: 10.5306/wjco.v7.i4.331 -
Clinical Breast Cancer Oct 2016Metastatic breast cancer (MBC) is treated with cytotoxic drugs or endocrine agents according to the site and extent of the disease, biology, previous treatments, and the... (Meta-Analysis)
Meta-Analysis Review
Metastatic breast cancer (MBC) is treated with cytotoxic drugs or endocrine agents according to the site and extent of the disease, biology, previous treatments, and the patient's condition, comorbidities, and wishes. In MBC, vinorelbine (VRB) and capecitabine (X; VRB + X) are chemotherapy drugs that hold activity as first or later lines of therapy. We conducted a systematic literature review and meta-analysis to quantify the efficacy of the VRB + X combination in HER2-negative (HER2) MBC. We searched PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library, and CINAHL for phase II/III clinical trials that assessed VRB + X for patients with HER2 MBC. Pooled estimates of the overall response rate (RR), median progression-free survival (PFS), and overall survival (OS) were computed using random or fixed effects models. Twenty-seven studies were included in the analysis, encompassing a total of 1356 MBC patients. All were phase II (n = 21) or prospective/pilot (n = 5) trials, except for 1 that was a phase III controlled trial. The pooled estimate for the RR in first-line therapy (n = 16 trials) was 52.9% (95% confidence interval [CI], 46.5%-59.2%). For second-line trials, data were available in n = 9 studies and the overall RR was 41% (95% CI, 31.2%-51.6%). The pooled estimates for median PFS and OS in first-line therapy were 7.3 (95% CI, 6.2-8.3) and 22.3 (95% CI, 20-24.5) months, respectively. Vinorelbine + X, with the dose and schedules currently used in clinical practice, appears to be an effective and feasible chemotherapy for MBC, for first- and also for second-line therapy.
Topics: Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease-Free Survival; Drug Administration Schedule; Feasibility Studies; Female; Humans; Receptor, ErbB-2; Taxoids; Treatment Outcome; Vinblastine; Vinorelbine
PubMed: 27282844
DOI: 10.1016/j.clbc.2016.05.002 -
Molecular and Clinical Oncology Sep 2015The present study aimed to compare the effects of vinorelbine-based neoadjuvant chemotherapy and vinorelbine-free regimens. A meta-analysis of all the relevant...
The present study aimed to compare the effects of vinorelbine-based neoadjuvant chemotherapy and vinorelbine-free regimens. A meta-analysis of all the relevant randomized controlled trials was performed to investigate the improvement in pathological complete response (pCR), overall response rate (ORR) and breast-conserving surgery (BCS). The PubMed and Embase databases were searched for relevant studies reporting randomized controlled trials comparing vinorelbine-based neoadjuvant chemotherapy with vinorelbine-free regimens until July 2013. Risk ratios/odds ratio and 95% confidence intervals (CIs) were used to estimate the association between vinorelbine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool the data. Five eligible studies with a total of 1,495 patients were included in the meta-analysis. Compared to vinorelbine-free chemotherapy, vinorelbine-based regimens demonstrated no significant improvement in clinical outcomes including: pCR [relative risk (RR)=1.016; 95% CI, 0.738-1.399; P=0.922], ORR (RR=1.048; 95% CI, 0.969-1.133; P=0.239) and BCS (RR=1.764; 95% CI, 0.734-4.239; P=0.205). However, vinorelbine-based regimens were associated with a lower incidence of grade 3-4 alopecia (OR, 0.617; 95% CI, 0.448-0.848; P=0.003). In a hierarchical analysis for patients who received neoadjuvant chemotherapy, the proportion of subjects achieving pCR was significantly increased when HER2-amplified (RR=2.31; 95% CI, 1.20-4.43; P=0.01) and hormone receptor negative (RR=0.488; 95% CI, 0.263-0.908; P=0.023). The present review confirms that neoadjuvant chemotherapy vinorelbine-based regimens are unlikely to emerge as superior to pCR, ORR and BCS. Hierarchical analysis indicated that the HER2-amplified and hormone receptor-negative patients were significantly associated with a pathological response rate.
PubMed: 26623067
DOI: 10.3892/mco.2015.576 -
Expert Review of Respiratory Medicine Oct 2015The aim of this systematic review is to assess the evidence for the available 2nd/3rd line systemic therapies for malignant pleural mesothelioma (MPM). Eligible studies... (Review)
Review
The aim of this systematic review is to assess the evidence for the available 2nd/3rd line systemic therapies for malignant pleural mesothelioma (MPM). Eligible studies were obtained through appropriate databases and meetings abstracts search. A total of 29 studies were considered eligible for this review and it includes three Phase III studies, eighteen phase II studies and eight retrospective studies. For the Phase III studies, none have achieved an overall survival benefit; while for the Phase II studies, the majority have not achieved sufficient satisfactory outcome to justify advancement to Phase III studies. We believe that the best salvage treatment for MPM would be inclusion into appropriately designed clinical trials. In the absence of a clinical trial, gemcitabine and/or vinorelbine-based regimens could be considered. Moreover, pemetrexed re-challenge can be considered in selected pemetrexed-sensitive patients.
Topics: Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms
PubMed: 26366804
DOI: 10.1586/17476348.2015.1083426 -
Thorax Apr 2015Our aim was to evaluate the clinical effectiveness of chemotherapy treatments currently licensed in Europe and recommended by the National Institute for Health and Care... (Meta-Analysis)
Meta-Analysis Review
Our aim was to evaluate the clinical effectiveness of chemotherapy treatments currently licensed in Europe and recommended by the National Institute for Health and Care Excellence (NICE) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). A systematic search of MEDLINE, EMBASE and the Cochrane Library for randomised controlled trials (RCTs) published from 2001 to 2010 was carried out. Relative treatment effects for overall survival (OS) and progression-free survival (PFS) were estimated using standard meta-analysis and mixed treatment comparison methodology. A total of 23 RCTs were included: 18 trials compared platinum-based chemotherapy, two compared pemetrexed and three compared gefitinib. There are no statistically significant differences in OS between any of the four third-generation chemotherapy regimens. There is statistically significant evidence that pemetrexed+platinum increases OS compared with gemcitabine+platinum. There are no statistically significant differences in OS between gefitinib and docetaxel+platinum or between gefitinib and paclitaxel+platinum. There is a statistically significant improvement in PFS with gefitinib compared with docetaxel+platinum and gefitinib compared with paclitaxel+platinum. Due to reduced generic pricing, third-generation chemotherapy regimens (except vinorelbine) are still competitive options for most patients. This research provides a comprehensive evidence base, which clinicians and decision-makers can use when deciding on the optimal first-line chemotherapy treatment regimen for patients diagnosed with locally advanced or metastatic NSCLC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; Drug Costs; Humans; Lung Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25661113
DOI: 10.1136/thoraxjnl-2014-205914 -
Health Technology Assessment... Jul 2013The National Institute for Health and Care Excellence (NICE) has issued multiple guidance for the first-line management of patients with lung cancer and recommends... (Review)
Review
Clinical effectiveness and cost-effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer: a systematic review and economic evaluation.
BACKGROUND
The National Institute for Health and Care Excellence (NICE) has issued multiple guidance for the first-line management of patients with lung cancer and recommends different combinations of chemotherapy treatments. This review provides a synthesis of clinical effectiveness and cost-effectiveness evidence supporting current guidance.
OBJECTIVES
To evaluate the clinical effectiveness and cost-effectiveness of first-line chemotherapy currently licensed in Europe and recommended by NICE, for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).
DATA SOURCES
Three electronic databases (MEDLINE, EMBASE and The Cochrane Library) were searched from 2001 to August 2010.
REVIEW METHODS
Trials that compared first-line chemotherapy currently licensed in Europe and recommended by NICE in chemotherapy-naive adult patients with locally advanced or metastatic NSCLC were included. Data on key outcomes including, but not limited to, overall survival (OS), progression-free survival (PFS) and adverse events (AEs) were extracted. For the assessment of cost-effectiveness, outcomes included incremental cost per quality-adjusted life-year (QALY) gained. Analyses were performed for three NSCLC subpopulations: patients with predominantly squamous disease, patients with predominantly non-squamous disease and patients with epidermal growth factor receptor (EGFR) mutation-positive (M+) status. Meta-analysis and mixed-treatment comparison methodology were conducted where appropriate.
RESULTS
Twenty-three trials involving > 11,000 patients in total met the inclusion criteria. The quality of the trials was poor. In the case of patients with squamous disease, there were no statistically significant differences in OS between treatment regimes. The mixed-treatment comparison demonstrated that, in patients with non-squamous disease, pemetrexed (Alimta®, Eli Lilly and Company; PEM) + platinum (PLAT) increases OS statistically significantly compared with gemcitabine (Gemzar®, Eli Lilly and Company; GEM) + PLAT [hazard ratio (HR) = 0.85; 95% confidence interval (CI) 0.74 to 0.98] and that paclitaxel (Abraxane®, Celgene Corporation; PAX) + PLAT increases OS statistically significantly compared with docetaxel (Taxotere®, Sanofi-aventis; DOC) + PLAT (HR = 0.79, 95% CI 0.66 to 0.93). None of the comparisons found any statistically significant differences in OS among patients with EGFR M+ status. Direct meta-analysis showed a statistically significant improvement in PFS with gefitinib (Iressa®, AstraZeneca; GEF) compared with DOC + PLAT and PAX + PLAT (HR = 0.49; 95% CI 0.33 to 0.73; and HR = 0.38; 95% CI 0.24 to 0.60, respectively). No papers related to UK decision-making were identified. A de novo economic model was developed. Using list prices (British National Formulary), cisplatin (CIS) doublets are preferable to carboplatin doublets, but this is reversed if electronic market information tool prices are used, in which case drug administration costs then become more important than drug acquisition costs. For patients with both squamous and non-squamous disease, moving from low to moderate willingness-to-pay thresholds, the preferred drugs are PAX → GEM → DOC. However, in patients with non-squamous disease, PEM + CIS resulted in increased OS and would be considered cost-effective up to £35,000 per QALY gained. For patients with EGFR M+, use of GEF compared with PAX or DOC yields very high incremental cost-effectiveness ratios. Vinorelbine (Navelbine®, Pierre Fabre Pharmaceutical Inc.) was not shown to be cost-effective in any comparison.
LIMITATIONS
Poor trial quality and a lack of evidence for all drug comparisons complicated and limited the data analysis. Outcomes and adverse effects are not consistently combined across the trials. Few trials reported quality-of-life data despite their relevance to patients and clinicians.
CONCLUSIONS
The results of this comprehensive review are unique to NSCLC and will assist clinicians to make decisions regarding the treatment of patients with advanced NSCLC. The design of future lung cancer trials needs to reflect the influence of factors such as histology, genetics and the new prognostic biomarkers that are currently being identified. In addition, trials will need to be adequately powered so as to be able to test for statistically significant clinical effectiveness differences within patient populations. New initiatives are in place to record detailed information on the precise chemotherapy (and targeted chemotherapy) regimens being used, together with data on age, cell type, stage of disease and performance status, allowing for very detailed observational audits of management and outcomes at a population level. It would be useful if these initiatives could be expanded to include the collection of health economics data.
FUNDING
The National Institute for Health Research Health Technology Assessment.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Clinical Trials as Topic; Cost-Benefit Analysis; ErbB Receptors; Humans; Lung Neoplasms; Neoplasm Metastasis; Quality-Adjusted Life Years
PubMed: 23886301
DOI: 10.3310/hta17310 -
The Breast Journal 2013The purpose of this study was to investigate the efficacy and safety profile of vinorelbine-based chemotherapy in different settings for the treatment of breast cancer.... (Meta-Analysis)
Meta-Analysis Review
The purpose of this study was to investigate the efficacy and safety profile of vinorelbine-based chemotherapy in different settings for the treatment of breast cancer. We performed a computerized search using combinations of the following keywords: "breast cancer", "breast neoplasms", "trial", "vinorelbine" and "navelbine". A total of 20 trials were included in this analysis, with a total of 5,080 patients accrued. Taxane was associated with enhanced overall survival (OS; p = 0.027) and response rate (RR; p = 0.037) as compared with vinorelbine in monotherapy, but did not show significantly favored progression-free survival (PFS; p = 0.136). Vinorelbine alone was equivalent to fluoropyrimidine treatment in RR (p = 0.79) for the treatment of metastatic breast cancer. For vinorelbine-combined regimens, the analysis showed that the vinorelbine group gave similar results as other regimens for OS (p = 0.849) and PFS (p = 0.143). The RR of vinorelbine-combined regimens was slightly better than that of the other regimens (OR, 1.17), but the difference was not statistically significant. In neoadjuvant setting, vinorelbine treatment was as active as AC (doxorubicin, cyclophosphamide) or DAC (doxorubicin, cyclophosphamide, docetaxel) regimens with respect to RR (p = 0.76) and pathologic complete response (pCR; p = 0.77), but showed lower occurrence of grade 3/4 adverse effects. The analysis also demonstrated that vinorelbine-containing therapy is effective as adjuvant, front-line or salvage therapy of metastatic breast cancer, even for patients who were previously treated with anthracyclines or taxanes.
Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Deoxycytidine; Disease-Free Survival; Doxorubicin; Female; Fluorouracil; Humans; Neoadjuvant Therapy; Randomized Controlled Trials as Topic; Salvage Therapy; Taxoids; Treatment Outcome; Vinblastine; Vinorelbine
PubMed: 23320984
DOI: 10.1111/tbj.12071