Effectiveness and safety of pemetrexed-based doublet versus pemetrexed alone as second-line treatment for advanced non-small-cell lung cancer: a systematic review and meta-analysis
ABSTRACT To compared pemetrexed-based doublet with single-agent pemetrexed as second-line treatment for advanced non-small-cell lung cancer
We systematically searched for randomized clinical trials that compared pemetrexed-based doublet with single-agent pemetrexed in patients with histologically proven non-small-cell lung cancer. The primary end point was overall survival. Secondary end points were progression-free survival, overall response rate and grade 3 or 4 toxicity. Data were extracted from the studies by 2 independent reviewers. The meta-analysis was performed by Stata version 10.0 software (Stata Corporation, College Station, Texas, USA).
Five randomized clinical trials (totally 1,186 patients) were eligible. Meta-analysis showed that there was significant improvement in PFS (HR 0.82, 95% CI 0.71-0.95, P = 0.007) and overall response rate (OR 2.39, 95% CI 1.58-3.62, P = 0.000) in pemetrexed-based doublet group, compared with pemetrexed alone, though the pooled HR for overall survival (HR 0.89, 95% CI 0.76-1.04; P = 0.129) showed no significant difference between the two groups. However, there were more incidences of grade 3 or 4 neutropenia (OR 2.3, 95% CI 1.4-3.77, P = 0.001), thrombocytopenia (OR 6.41, 95% CI 2.57-16.0, P = 0.000), and leucopenia (OR 2.45, 95% CI 1.13-5.34, P = 0.024) in pemetrexed-based doublet group. With regard to the risk of grade 3 or 4 anemia (OR 0.71, 95% CI 0.17-2.91, P = 0.629) and fatigue (OR 1.47, 95% CI 0.92-2.35, P = 0.104), there was no significant difference between the two groups.
Pemetrexed-based doublet therapy didn't gain any benefit in survival but significantly improved PFS and better ORR compared with single-agent pemetrexed as second-line therapy for advanced non-small-cell lung cancer. However, more incidences of grade 3 or 4 neutropenia, thrombocytopenia, and leucopenia were observed in pemetrexed-based doublet group.
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ABSTRACT: Purpose: To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitormonotherapy (EFGR-TKIs: gefitinib or erlotinib) with standard second-line chemotherapy (single agent docetaxel or pemetrexed) in previously treated advanced non-small-cell lung cancer (NSCLC). Methods: We systematically searched for randomized clinical trials that compared EGFR-TKI monotherapy with standard second-line chemotherapy in previously treated advanced NSCLC. The end points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), 1-year survival rate (1-year SR) and grade 3 or 4 toxicities. The pooled hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: Eight randomized controlled trials (totally 3218 patients) were eligible. Our meta-analysis results showed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced NSCLC in terms of overall survival (HR 1.00, 95%CI 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI 0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall response rate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000). Sub-group analysis demonstrated that EGFR-TKI monotherapy significantly improved PFS (HR 0.73, 95%CI: 0.55-0.97, p=0.03) and ORR (RR 1.96, 95%CI: 1.46-2.63, p=0.000) in East Asian patients, but it did not translate into increase in OS and 1-year SR. Furthermore, there were fewer incidences of grade 3 or 4 neutropenia, febrile neutropenia and neutrotoxicity in EGFR-TKI monotherapy group, excluding grade 3 or 4 rash. Conclusion: Both interventions had comparable efficacy as second-line treatments for patients with advanced NSCLC, and EGFR-TKI monotherapy was associated with less toxicity and better tolerability. Moreover, our data also demonstrated that EGFR- TKImonotherapy tended to be more effective in East Asian patients in terms of PFS and ORR compared with standard second-line chemotherapy. These results should help inform decisions about patient management and design of future trials.Asian Pacific journal of cancer prevention: APJCP 10/2012; 13(10):5177-82. DOI:10.7314/APJCP.2012.13.10.5177 · 1.50 Impact Factor
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ABSTRACT: The inhibitory effects of magnetic fields (MFs) on tumor cell proliferation in vitro and in vivo have been reported in previous studies. However, the effects of MFs in the treatment of cancer have not been described in clinical trials. We investigated the effects of 420 r/min, 0.4-T extremely low-frequency MFs (ELF-MFs) on the survival and palliation of general symptoms in 13 advanced non-small cell lung cancer (NSCLC) patients. Toxicity and side-effects were assessed according to WHO criteria. The treatment area included the primary tumor site, metastatic sites and metastatic lymph nodes. Additionally, the patients were treated 2 h per day, 5 days per week for 6-10 weeks. The changes in general symptoms were analyzed during ELF-MF treatment and 2 weeks after the completion of therapy. Results of physical examination, routine analysis of blood, ECG and liver function, biochemical and kidney function tests were evaluated before and following treatment. All 13 patients were followed up by outpatient service or telephone interview. Our results demonstrated that decreased pleural effusion, remission of shortness of breath, relief of cancer pain, increased appetite, improved physical strength, regular bowel movement and better sleep quality was detected in 2 (15.4%), 5 (38.5%), 5 (38.5%), 6 (46.2%), 9 (69.2%), 1 (7.7%) and 2 (15.4%) patients, respectively. However, the palliation of symptoms in 2 (15.4%) patients was observed during therapy and disappeared at treatment termination. No severe toxicity or side-effects were detected in our trial. The median survival was 6.0 months (95% CI, 1.0-11.0). The 1- and 2-year survival rates were 31.7 and 15.9%, respectively. This study is the first to describe survival and palliation of general symptoms in advanced NSCLC patients treated with ELF-MFs. As an effective, well-tolerated and safe treatment choice, ELF-MFs may prolong survival and improve general symptoms of advanced NSCLC patients. However, this treatment strategy requires further research.Oncology letters 11/2012; 4(5):1130-1134. DOI:10.3892/ol.2012.867 · 0.99 Impact Factor
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ABSTRACT: Introduction: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide. Although advanced NSCLC is still incurable, various anti-neoplastic agents have become available for the treatment of this disease. Pemetrexed , a multi-target folate antagonist, has improved the survival of non-squamous NSCLC patients. Currently, pemetrexed is approved for first-line treatment in combination with a platinum derivate, for second-line treatment as a single agent and, more recently, as maintenance treatment after first-line chemotherapy. Areas covered: The authors analyzed the state of the art of pemetrexed through a review of the literature. Clinical trials and meta-analyses involving pemetrexed in NSCLC were evaluated. Pemetrexed improved survival of non-squamous NSCLC in first-line, maintenance, and second-line treatments; this benefit is limited to non-squamous histology. Because pemetrexed has become part of the standard of care, current clinical trials are designed to compare it to other investigational combinations. Limited data on resectable disease are available, and additional clinical trials are being conducted. Expert opinion: Pemetrexed has shown effectiveness and a favorable toxicity profile. Histology-driven indications and the relationship of pemetrexed with thymidylate synthase expression suggest that a more precise definition of predictive biomarkers could be further investigated.Expert Opinion on Pharmacotherapy 05/2013; DOI:10.1517/14656566.2013.802774 · 3.09 Impact Factor