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Cureus Jan 2023Current non-small cell lung cancer (NSCLC) treatment consists of various combinations of surgery, chemotherapy, and/or radiation, depending on the tumor stage.... (Review)
Review
Current non-small cell lung cancer (NSCLC) treatment consists of various combinations of surgery, chemotherapy, and/or radiation, depending on the tumor stage. Individuals with stage II-IIIa NSCLC undergo surgery, followed by combination chemotherapy containing cisplatin, such as vinorelbine + cisplatin. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib, act by inhibiting any signaling pathway containing the EGFR mutation and inhibiting the growth of NSCLC. TKI is a treatment option in advanced NSCLC, resulting in more prolonged progression-free survival (PFS). This manuscript aims to evaluate the influence of utilizing gefitinib - either alone or in combination with conventional chemotherapeutic drug regimens upon NSCLC patient profile survival parameters. A systematic literature review was conducted across multiple scientific literature repositories. The review was performed using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020. There were six randomized clinical trials (RCT) and five retrospective studies. The overall consensus based on the end outcome of each published journal on the effectiveness of gefitinib as a treatment option for NSCLC indicated that there was a notable difference in overall survival (OS) and progression-free survival (PFS) and disease-free survival (DFS) datasets. Gefitinib use correlated with increased timeframes for multiple patient survival parameters within articles shortlisted in this investigation. However, more comprehensive investigations are required to validate such correlations. Gefitinib did demonstrate the potential to provide beneficial effects and counteract NSCLC within such patients.
PubMed: 36788891
DOI: 10.7759/cureus.33691 -
Journal of Cancer 2021Different second-line treatments of patients with trastuzumab-resistant human epidermal growth factor receptor 2 (HER2) positive breast cancer were examined in...
Efficacy of second-line treatments for patients with advanced human epidermal growth factor receptor 2 positive breast cancer after trastuzumab-based treatment: a systematic review and bayesian network analysis.
Different second-line treatments of patients with trastuzumab-resistant human epidermal growth factor receptor 2 (HER2) positive breast cancer were examined in randomized controlled trials (RCTs). A network meta-analysis is helpful to evaluate the comparative survival benefits of different options. We performed a bayesian network meta-analysis using R-4.0.0 software and fixed consistency model to compare the progression free survival (PFS) and overall survival (OS) benefits of different second-line regimens. 13 RCTs (19 publications, 4313 patients) remained for qualitative synthesis and 12 RCTs (17 publications, 4022 patients) were deemed eligible for network meta-analysis. For PFS, we divided network analysis into two parts owing to insufficient connections among treatments. The first part involved 8 treatments in 9 studies and we referred it as PFS (#1). Amid the following 8 interventions: pyrotinib + capecitabine, T-DM1 + atezolizumab, pertuzumab + trastuzumab + capecitabine, T-DM1, trastuzumab + capecitabine, lapatinib + capecitabine, neratinib, and capecitabine, we found consistent benefits between the first three interventions; moreover, pyrotinib + capecitabine was most likely to be associated with the best benefits; capecitabine monotherapy was associated with the worst PFS. The second part included 3 treatments in 2 studies and we referred it as PFS (#2): everolimus + trastuzumab + vinorelbine had better PFS benefits versus trastuzumab + vinorelbine and afatinib + vinorelbine. For OS, we analyzed 7 treatments in 7 studies, and observed T-DM1 + atezolizumab, pertuzumab + trastuzumab + capecitabine, and T-DM1 had similar effectiveness, and the first had the highest probability to yield the longest OS; capecitabine or neratinib alone yielded the worst OS benefits. Our work comprehensively summarized and analyzed current available RCT-based evidence of the second-line treatments for trastuzumab-treated, HER2-positive, advanced breast cancer. These results provide clinicians and oncologists meaningful references for clinical drug administration and the development of novel effective therapies.
PubMed: 33613756
DOI: 10.7150/jca.51845 -
Acta Oncologica (Stockholm, Sweden) Sep 2020Overall prognosis of advanced sarcoma remains poor, optimization of systemic treatment is urgently needed in this setting. We systematically reviewed fully published...
Overall prognosis of advanced sarcoma remains poor, optimization of systemic treatment is urgently needed in this setting. We systematically reviewed fully published English-speaking literature about maintenance therapy and drug holiday in sarcoma patients management. We found that switch maintenance therapy with cyclophosphamide/vinorelbine improves the outcome of localized high-risk rhabdomyosarcoma. There is no other maintenance therapy recommended in sarcoma patients. After classical chemotherapy, maintenance therapy with immune-stimulating agents for localized osteosarcoma, bevacizumab for advanced angiosarcoma or pediatric advanced sarcoma, or mTOR inhibitors for metastatic sarcoma does not improve the outcome. Drug holiday has been assessed for metastatic gastrointestinal stromal tumor treated with imatinib as the first-line therapy or for metastatic soft-tissue sarcoma treated with trabectedin. Drug holiday has been found to lead to rapid disease progression and should be avoided. Data about both maintenance and drug holiday are spare in sarcoma management.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cyclophosphamide; Disease-Free Survival; Drug Administration Schedule; Drug Substitution; Hemangiosarcoma; Humans; Maintenance Chemotherapy; Osteosarcoma; Prognosis; Rhabdomyosarcoma; Survival Rate; Trabectedin; Vinorelbine
PubMed: 32400254
DOI: 10.1080/0284186X.2020.1759825 -
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 -
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 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 -
BMJ Open Jun 2022This study aimed to compare the efficacy and safety of different platinum adjuvant chemotherapy regimens for early-stage resected non-small-cell lung cancer (NSCLC). (Meta-Analysis)
Meta-Analysis
Investigation of the optimal platinum-based regimen in the postoperative adjuvant chemotherapy setting for early-stage resected non-small lung cancer: a Bayesian network meta-analysis.
OBJECTIVE
This study aimed to compare the efficacy and safety of different platinum adjuvant chemotherapy regimens for early-stage resected non-small-cell lung cancer (NSCLC).
DESIGN
Systematic review with network meta-analysis of randomised trials.
DATA SOURCES
PubMed, EMBASE, The Cochrane Library, Web of Science and Scopus Google Scholar were searched through 12 March 2021.
ELIGIBILITY CRITERIA
Eligible randomised controlled trials (RCTs) comparing the postoperative platinum chemotherapy regimen with the observation-controlled group or comparing two platinum chemotherapy regimens head-to-head were included.
DATA EXTRACTION AND SYNTHESIS
The primary outcome was the efficacy of adjuvant chemotherapy regimens including relapse-free survival (RFS), overall survival (OS), 2-year, 3-year, 5-year RFS rate and OS rate. The secondary outcome was the rate of grade 3-4 toxicity assessments. Cochrane Handbook (V.5) was used for the risk of bias assessment. Analyses were performed using R software V.4.3.1.
RESULTS
20 RCTs with a sample size of 5483 were enrolled in meta-analysis. The chemotherapy group had a significant RFS and OS advantage compared with the observation group (HR 0.67; 95% CI 0.56 to 0.81, p<0.0001; HR 0.80; 95% CI, 0.73 to 0.88, p<0.0001, respectively). Compared with the observation arm, only the 'cisplatin_vinorelbine' regimen had a significant RFS and OS advantage (HR 0.63; 95% CI 0.43 to 0.87; HR 0.74; 95% CI 0.63 to 0.87, respectively) while the remaining chemotherapy regimens had no significant difference of efficacy compared with the observation group. In terms of the safety of adjuvant chemotherapy, the incidence of haematological toxicities and nausea/vomiting was not significantly higher in the 'cisplatin_vinorelbine' arm than in other chemotherapy group.
CONCLUSION
This study summarised the adjuvant cytotoxicity chemotherapy regimens for patients with early-stage resected NSCLC. Our analysis may provide some guiding significance for the clinicians when determining the optimal chemotherapy regimen.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Cisplatin; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Network Meta-Analysis; Platinum; Vinorelbine
PubMed: 35697451
DOI: 10.1136/bmjopen-2021-057098 -
Bulletin Du Cancer Oct 2019Adenoid Cystic Carcinoma is a rare tumor of the head and neck sphere. The purpose of this review is a state of the art of systemic treatments (chemotherapies, targeted...
INTRODUCTION
Adenoid Cystic Carcinoma is a rare tumor of the head and neck sphere. The purpose of this review is a state of the art of systemic treatments (chemotherapies, targeted therapies, immunotherapies) for locally recurrent or metastatic disease.
MATERIAL AND METHODS
Our inclusion criteria included head and neck adult patient, metastatic or locally advanced, treated by a systemic therapy, and with at least 10 or more patients.
RESULTS
Forty articles have been selected in this review. The objective response rate under chemotherapy was predominantly<10% (0-70%) with objective responses in monotherapy with cisplatin, mitoxantrone, vinorelbine and eribuline, and with cisplatin-vinorelbine combination. EGFR inhibitors provided 40% objective responses only in combination. Inhibitors of VEGF and histone deacetylase have allowed disease stabilization in progressive patients, with about 10% of objective response. Inhibitors of c-KIT monotherapy yield objective response rates of<5%. Direct inhibitors of the PI3K/AKT/mTOR pathway display 0% objective response rate.
CONCLUSION
The best objective response rates were obtained with cisplatin-vinorelbine combination. Many targetable molecular abnormalities have been identified and studies have shown prolonged stabilization with EGFR, VEGF and HDAC inhibitors. Multi-disciplinary collaborative consultation (MCC) meetings such as French network of experts in rare head and neck tumors (REFCOR) or Molecular MCC should be proposed and may allow referral to centers proposing specific therapeutic trials.
Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenoid Cystic; ErbB Receptors; Humans; Immunotherapy; Molecular Targeted Therapy; Neoplasm Recurrence, Local; Otorhinolaryngologic Neoplasms; Rare Diseases; Treatment Outcome; Vascular Endothelial Growth Factor A
PubMed: 31324333
DOI: 10.1016/j.bulcan.2019.05.003