scholarly journals Anlotinib for refractory advanced non-small-cell lung cancer: A systematic review and meta-analysis

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242982
Author(s):  
Guocan Yu ◽  
Yanqin Shen ◽  
Xudong Xu ◽  
Fangming Zhong
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Hazard Ratios ◽  
Clinical Benefits ◽  
Grade 3

Objective To assess the efficacy and toxicity of anlotinib for the treatment of refractory advanced non-small-cell lung cancer (NSCLC). Methods We systematically searched databases for randomized controlled trials on anlotinib treatment for patients with advanced NSCLC published until November 6, 2020. Articles were assessed and data were extracted independently by two investigators. Further, we analyzed hazard ratios (HRs) for progression-free and overall survival (PFS and OS, respectively). In addition, we analyzed risk ratio (RR) for overall response and disease control rates (ORR and DCR, respectively) and the odds ratio (OR) for the main adverse events (AEs) using RevMan 5.3 software. Results This analysis included 594 patients from three clinical studies. The pooled HRs for PFS and OS were 0.27 (95% confidence interval (CI): 0.22–0.33, P < 0.001) and 0.68 (95% CI: 0.56–0.83, P < 0.001), respectively, indicating that anlotinib administration significantly improved PFS and OS in patients with advanced NSCLC. The pooled RRs for ORR and DCR were 11.62 (95% CI: 2.75–49.14, P < 0.001) and 2.30 (95% CI: 1.91–2.77, P < 0.001), respectively, indicating that anlotinib administration in patients with advanced NSCLC improved ORR and DCR. The pooled OR for AEs of grade 3 or higher was 2.94 (95% CI: 1.99–4.35, P < 0.001), indicating that AEs of grade 3 or higher were more prevalent in the anlotinib group than in the placebo group. Conclusion Anlotinib, an effective choice of third- or later line therapy for patients with refractory advanced NSCLC, provides clinical benefits in terms of PFS, OS, ORR, and DCR. AEs associated with anlotinib were tolerable.

scholarly journals A systematic review and meta-analysis of treatment-related toxicities of curative and palliative radiation therapy in non-small cell lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Or ◽  
B. Liu ◽  
J. Lam ◽  
S. Vinod ◽  
W. Xuan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Decision Making ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cardiac Events ◽  
Grade 3

AbstractTreatment-related toxicity is an important component in non-small cell lung cancer (NSCLC) management decision-making. Our aim was to evaluate and compare the toxicity rates of curative and palliative radiotherapy with and without chemotherapy. This meta-analysis provides better quantitative estimates of the toxicities compared to individual trials. A systematic review of randomised trials with > 50 unresectable NSCLC patients, treated with curative or palliative conventional radiotherapy (RT) with or without chemotherapy. Data was extracted for oesophagitis, pneumonitis, cardiac events, pulmonary fibrosis, myelopathy and neutropenia by any grade, grade ≥ 3 and treatment-related deaths. Mantel–Haenszel fixed-effect method was used to obtain pooled risk ratio. Forty-nine trials with 8609 evaluable patients were included. There was significantly less grade ≥ 3 acute oesophagitis (6.4 vs 22.2%, p < 0.0001) and any grade oesophagitis (70.4 vs 79.0%, p = 0.04) for sequential CRT compared to concurrent CRT, with no difference in pneumonitis (grade ≥ 3 or any grade), neutropenia (grade ≥ 3), cardiac events (grade ≥ 3) or treatment-related deaths. Although the rate of toxicity increased with intensification of treatment with RT, the only significant difference between treatment regimens was the rate of oesophagitis between the use of concurrent and sequential CRT. This can aid clinicians in radiotherapy decision making for NSCLC.

scholarly journals Nivolumab plus Ipilimumab versus Existing Immunotherapies in Patients with PD-L1-Positive Advanced Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1905 ◽  
Author(s):  
Koichi Ando ◽  
Yasunari Kishino ◽  
Tetsuya Homma ◽  
Sojiro Kusumoto ◽  
Toshimitsu Yamaoka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Outcome Analysis ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy

No head-to-head trials have compared the efficacy and safety of nivolumab (Niv) plus ipilimumab (Ipi) combination therapy (Niv+Ipi) and existing regimens with immunotherapies approved as first-line treatment in patients with programmed cell death ligand 1 (PD-L1)-positive previously untreated advanced non-small cell lung cancer (NSCLC). We conducted a network meta-analysis of four relevant Phase Ⅲ trials to compare the efficacy and safety of Niv+Ipi, pembrolizumab (Pem) plus platinum-based chemotherapy (PBC) (Pem+PBC), Pem, Niv, or PBC using Bayesian analysis. The primary efficacy endpoint was progression-free survival (PFS) in patients with advanced NSCLC with PD-L1 expression ≥1%. The primary safety endpoint was the incidence of Grade 3–5 drug-related adverse events (G3–5AEs). Efficacy and safety were ranked using surface under the cumulative ranking curve (SUCRA). With regard to PFS, Niv+Ipi was inferior to Pem+PBC, and superior to Pem, Niv, or PBC alone. SUCRA ranking showed Pem+PBC had the highest efficacy for PFS, followed by Niv+Ipi, Niv, PBC, and Pem. The safety outcome analysis revealed Niv+Ipi was generally well tolerated compared to existing immunotherapy regimens. These results provide clinical information regarding the efficacy and safety of Niv+Ipi and indicate the possibility of the Niv+Ipi combination as a new therapeutic option in PD-L1-positive advanced NSCLC.

Randomized Phase III Study of Gemcitabine-Cisplatin Versus Etoposide-Cisplatin in the Treatment of Locally Advanced or Metastatic Non–Small-Cell Lung Cancer

1999 ◽  
Vol 17 (1) ◽  
pp. 12-12 ◽  
Author(s):  
Felipe Cardenal ◽  
M. Paz López-Cabrerizo ◽  
Antonio Antón ◽  
Vicente Alberola ◽  
Bartomeu Massuti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non–small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. PATIENTS AND METHODS: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. RESULTS: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. CONCLUSION: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.

scholarly journals Efficacy and toxicities of combination maintenance therapy in the treatment of advanced non-small-cell lung cancer: an up-to-date meta-analysis

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Jianming Hu ◽  
Jiawei Hu ◽  
Xiaolan Liu ◽  
Long Li ◽  
Xue Bai
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3 ◽  
Nsclc Patients

Abstract Background: Single agent maintenance therapy has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC) due to its potential survival benefits, but whether combined maintenance therapy would improve the survival of advanced NSCLC remains undetermined. Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing combination maintenance therapy in advanced NSCLC patients were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and grade 3–4 toxicities. Results: A total of 1950 advanced NSCLC patients received combination maintenance treatment from six trials were included for analysis. The use of doublet maintenance therapy in NSCLC patients significantly improved PFS (HR 0.74, 95%CI: 0.59–0.93, P = 0.010), but not for OS (HR 0.95, 95%CI: 0.85–1.07, P = 0.40) in comparison with single agent maintenance therapy. Similar results were observed in sub-group analysis according to treatment regimens. In addition, there was no significantly risk difference between doublet and single agent maintenance therapy in terms of grade 3/4 hematologic and non-hematologic toxicities. Conclusion: The findings of the present study show that doublet combination maintenance therapy is superior to single agent maintenance therapy in terms of PFS, without increased grade 3–4 toxicities. Future prospective studies are recommended to clearly assess the long-term clinical benefit of doublet maintenance therapy and its impact on health-related quality of life.

Randomized phase III trial of S-1 plus cisplatin versus docetaxel plus cisplatin for advanced non-small-cell lung cancer (TCOG0701).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7515-7515 ◽  
Author(s):  
Nobuyuki Katakami ◽  
Akihiko Gemma ◽  
Hiroshi Sakai ◽  
Kaoru Kubota ◽  
Makoto Nishio ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

7515 Background: Although molecularly targeted therapy improves outcome of selected patients with advanced non-small-cell lung cancer (NSCLC), most of the patients ultimately become candidates of cytotoxic chemotherapy, which is the cornerstone of patient management. S-1 plus cisplatin (SP) has shown activity and good tolerability in phase II settings. Docetaxel plus cisplatin (DP) is the only third-generation regimen that demonstrated statistically significant improvement of overall survival and quality of life by head to head comparison with a second-generation regimen, vindesine plus cisplatin, in patients with advanced NSCLC. Methods: Patients with previously untreated stage IIIB or IV NSCLC, an ECOG PS of 0-1 and adequate organ functions were randomized to receive either oral S-1 80 mg/m2/day (40 mg/m2 b.i.d.) on days 1 to 21 plus cisplatin 60 mg/m2 on day 8 every 5 weeks or docetaxel 60mg/m2 on day 1 plus cisplatin 80 mg/m2 on day 1 every 3 weeks, both up to 6 cycles. The primary endpoint is overall survival (OS). Non-inferiority study design was employed as upper confidence interval (CI) limit for HR<1.322. Secondary endpoints include progression-free survival (PFS), response, safety, and quality of life (QOL). Results: From April 2007 to December 2008, 608 patients from 66 sites in Japan were randomized to SP (n=303) or DP (n=305). Patient demographics were well balanced between the two groups. Two interim analyses were preplanned. At the final analysis, total of 480 death events were observed. The primary endpoint was met. OS for SP was non inferior to DP (median survival, 16.1 v 17.1 months, respectively; HR=1.013; 96.4% CI, 0.837-1.227). PFS was 4.9 months in the SP arm and 5.2 months in the DP arm. Statistically significantly lower rate of febrile neutropenia (7.4% v 1.0%), grade 3/4 neutropenia (73.4% v 22.9%), grade 3/4 infection (14.5% v 5.3%), grade 1/2 alopecia (59.3% v 12.3%) were observed in the SP arm than in the DP arm. QOL data investigated by EORTC QLQ-C30 and LC-13 favored for the SP arm. Conclusions: S-1 plus cisplatin is a standard first-line chemotherapy regimen for advanced NSCLC.

scholarly journals Kanglaite Injection Combined with Chemotherapy versus Chemotherapy Alone for the Improvement of Clinical Efficacy and Immune Function in Patients with Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Jianxia Wen ◽  
Tao Yang ◽  
Jian Wang ◽  
Xiao Ma ◽  
Yuling Tong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Immune Function ◽  
Clinical Efficacy ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung

Recent advances have shown that immune checkpoint inhibitors are emerging as promising therapeutic targets to improve the quality of life in cancer patients. This meta-analysis was conducted to evaluate the influence of Kanglaite injection (KLTi) combined with chemotherapy versus chemotherapy alone on clinical efficacy, immune function, and safety for the treatment of advanced non-small-cell lung cancer (NSCLC). Several electronic databases, including PubMed, Web of Science, Wan-Fang, VMIS, EMBASE, Cochrane Library, CNKI, CBM, and MEDLINE, as well as grey literatures, were comprehensively searched from January 2000 to November 2019. Randomized controlled trials (RCTs) reporting outcomes of clinical efficacy and immune function were collected according to their inclusion and exclusion criteria. Cochrane Reviewers’ Handbook 5.2 was applied to assess the risk of bias of included trials. STATA 13.0 and Review Manager 5.3 software were used for meta-analysis. Twenty-five RCTs comprising 2151 patients meeting the inclusion criteria were identified. Meta-analysis showed that compared with chemotherapy alone, KLTi plus the same chemotherapy significantly improved clinical efficacy, including complete response, partial response, stable disease, and progressive disease, as well as immune function, including CD3+, CD4+, CD8+, and CD4+/CD8+. There was a significant reduction in nausea and vomiting, thrombocytopenia, and leukopenia in combination treatments. However, the outcomes were limited because of the low quality and small sample size of the included studies. In conclusion, this work might provide beneficial evidence of KLTi combined with chemotherapy for improving clinical efficacy and immune function, as well as reducing the incidence of adverse events in advanced NSCLC patients. KLTi might be a beneficial therapeutic method for the treatment of advanced NSCLC. Due to the quality of the data, more rigorous and well-designed RCTs are needed to confirm these findings.

Multitargeted Antifolate LY231514 as First-Line Chemotherapy for Patients With Advanced Non–Small-Cell Lung Cancer: A Phase II Study

1999 ◽  
Vol 17 (4) ◽  
pp. 1194-1194 ◽  
Author(s):  
James J. Rusthoven ◽  
Elizabeth Eisenhauer ◽  
Charles Butts ◽  
Richard Gregg ◽  
Janet Dancey ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Stage Iv ◽  
Small Cell ◽  
Stage Iiib ◽  
Small Cell Lung ◽  
Stage Iv Disease ◽  
Grade 3

PURPOSE: To evaluate the efficacy and safety of the multitargeted antifolate LY231514 (MTA) in patients receiving initial chemotherapy for unresectable, advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with measurable, advanced NSCLC who had not received previous chemotherapy for advanced disease were considered for this study. Eligible patients who gave written informed consent initially received MTA 600 mg/m2 intravenously (IV) for 10 minutes every 3 weeks. After three patients received treatment at this dose, the dose was reduced to 500 mg/m2 IV at the same infusion time and frequency because of toxicity seen in this study and another Canadian MTA trial in colorectal cancer. Patients received up to four cycles after complete or partial remission or six cycles after stable disease was documented. RESULTS: Thirty-three patients were accrued onto the study. All were assessable for toxicity, and 30 patients were assessable for response. All but one patient had an Eastern Cooperative Oncology Group performance status score of 0 or 1, 18 patients (55%) had adenocarcinoma, and nine patients (27%) had squamous cell carcinoma. Twenty-five patients (76%) had stage IV disease, and the remainder had stage IIIB disease at trial entry. Seven patients experienced a confirmed partial response and no complete responses were seen; thus, the overall response rate was 23.3% (95% confidence interval, 9.9% to 42.3%). The median duration of response was 3.1 months (range, 2.3 to 13.5 months) after a median follow-up period of 7.9 months. Four (67%) of six patients with stage IIIB disease and three (12.5%) of 24 with stage IV disease responded to treatment. Four patients (13.3%) experienced febrile neutropenia and 13 (39%) experienced grade 3 or 4 neutropenia, whereas only one patient (3%) developed grade 4 thrombocytopenia. Nonhematologic toxicity was generally mild or moderate, but 39% of patients developed a grade 3 skin rash. Most other toxicities comprised grade 1 or 2 stomatitis, diarrhea, lethargy, and anorexia. Ten patients stopped protocol therapy because of toxicity. CONCLUSION: MTA seems to have clinically meaningful activity as a single agent against advanced NSCLC. Toxicity is generally mild and tolerable. Further study of this agent in combination with cisplatin and other active drugs is warranted in this disease.

Phase II study of irinotecan plus S-1 combination for previously untreated advanced non-small cell lung cancer: Hokkaido Lung Cancer Clinical Study Group 0601

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19012-e19012
Author(s):  
S. Oizumi ◽  
K. Akie ◽  
S. Ogura ◽  
N. Shinagawa ◽  
S. Fukumoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Small Cell ◽  
Severe Toxicity ◽  
Small Cell Lung ◽  
Grade 3

e19012 Background: Platinum-containing therapy is a standard first-line treatment for advanced non-small cell lung cancer (NSCLC). Platinum-free regimens can be alternative if they can provide similar efficacy with better tolerability. This study evaluated the efficacy and safety for combination of irinotecan and S-1, a newly developed oral 5-fluorouracil derivative, for chemotherapy-naïve advanced NSCLC. Methods: In this multicenter phase II trial, we initially planned to enroll 40 patients. Chemotherapy consisted of 4-week cycles of irinotecan (100 mg/m2 IV, day 1 and 15) and S-1 (80 mg/m2 orally, day 1–14). Primary end point was response rate; secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. Association of UGT1A1 genotypes (*6 and *28) with frequency of severe toxicity was also examined. Results: A total of 112 cycles was administered into 40 patients (median, 3 cycles: range, 1–6). Median age was 64 years (range, 42–75); 29 patients (73%) had adenocarcinoma, and 8 patients (20%) had squamous cell carcinoma. Majority of the patients (32 cases, 80%) had stage IV disease. Twelve patients exhibited partial response (PR), and 17 patients exhibited stable disease (SD), resulting in response rate of 30% [95% confidence interval (95% CI), 16.6–46.5] and disease control rate of 72.5% (95% CI, 56.1–85.4). Median OS and PFS were 13.8 months (95% CI, 10.7–16.9) and 4.7 months (95% CI, 3.4–6.0), respectively. Hematological toxicities of grade 3 or 4 were neutropenia (32.5%) and anemia (5.0%). The most common non-hematologic toxicities of grade 3 or 4 included diarrhea (15.0%) and anorexia (17.5%). There were no treatment-related deaths. Among the 40 patients, there were 1 homozygous and 8 heterozygous for UGT1A1*6, whereas 7 heterozygous for UGT1A1*28; none of the patients had both genotypes. Patients with homozygous or heterozygous for UGT1A1*6 showed a trend for high incidence of grade 3 diarrhea (p = 0.055). No association of UGT1A1*28 with severe toxicity was observed in this study. Conclusions: Irinotecan and S-1 combination is an alternative treatment with tolerable toxicity for previously untreated advanced NSCLC. No significant financial relationships to disclose.

scholarly journals Shenfu Injection Adjunct with Platinum-Based Chemotherapy for the Treatment of Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis and Systematic Review

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Ailing Cao ◽  
Hailang He ◽  
Mengxin Jing ◽  
Beibei Yu ◽  
Xianmei Zhou
Keyword(s):  
Lung Cancer ◽  
Adverse Effects ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Shenfu Injection ◽  
Platinum Based Chemotherapy

Platinum-based chemotherapy is one of the standard treatments for non-small-cell lung cancer (NSCLC), while its high toxicity and limited clinical effects raise big concerns. Shenfu injection (SFI) has been commonly used as an adjutant chemotherapy drug for NSCLC in China. We ascertained the beneficial and adverse effects of SFI in combination with platinum-based chemotherapy for advanced NSCLC by using meta-analysis methods. The randomized controlled trials (RCTs) involving advanced NSCLC treatment with SFI plus platinum-based chemotherapy versus chemotherapy alone were searched on 6 medical databases up to February 2017. Cochrane handbook 5.1.0 was applied to assess the quality of included trials and RevMan 5.3 software was employed for data analysis. 23 RCTs including 1574 patients met our inclusion criteria. We evaluated the following outcome measures: objective tumor response (ORR), disease control rate (DCR), Karnofsky performance score (KPS), adverse effects, and indicators of cellular immune function. The meta-analysis indicated that SFI plus platinum-based chemotherapy may benefit the patients with NSCLC on attenuated synergies of chemotherapy. These findings need to be confirmed by further rigorously designed high-quality and large-scale RCTs.

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