This study analyzed data from 5 clinical trials comparing the effects of filgrastim and pegfilgrastim (G-CSF) to placebo in patients receiving chemotherapy. The results showed:
1) Patients receiving G-CSF had significantly lower rates of severe neutropenia and febrile neutropenia after the first cycle of chemotherapy compared to placebo.
2) Median overall survival was greater for patients receiving G-CSF versus placebo in one lung cancer trial, but the differences were not statistically significant.
3) A meta-analysis of the 3 placebo-controlled trials found a hazard ratio for overall survival of 0.77 favoring G-CSF over placebo, but again the result was not statistically significant. Further studies are
1. A randomized trial compared restrictive (transfuse if Hb <7 g/dL) vs liberal (transfuse if Hb <9 g/dL) transfusion strategies in critically ill cancer patients with septic shock.
2. At 28 days, all-cause mortality was not significantly different between groups. However, at 90 days mortality was significantly higher in the restrictive group.
3. Secondary outcomes including ventilation, renal replacement therapy, inotropes, and length of stay showed no significant differences.
4. The results suggest a liberal transfusion strategy may be preferable for critically ill cancer patients with septic shock, as a restrictive strategy was associated with higher 90-day mortality.
Concurrent weekly single cisplatin vs triweekly cisplatin aloneHarihar Nath Tiwari
This document summarizes a meta-analysis comparing weekly vs triweekly cisplatin chemotherapy with radiotherapy for locally advanced cervical cancer. The analysis found no significant difference in 5-year overall survival or distant recurrence rates between the two regimens. However, the triweekly regimen was associated with higher treatment compliance and a higher risk of leucopenia as an acute adverse effect. In conclusion, triweekly cisplatin appeared superior for local recurrence and treatment compliance.
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Mina Max
This meta-analysis examined 12 randomized controlled trials involving 6,844 patients with advanced non-small cell lung cancer (NSCLC). The analysis compared chemotherapy with or without gefitinib. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The meta-analysis found that gefitinib therapy significantly improved PFS compared to chemotherapy alone, but only modestly improved OS and this difference was not statistically significant. Gefitinib therapy was associated with higher objective response rates. The most common adverse events with gefitinib were rash, diarrhea, and dry skin.
This document summarizes key milestones in the treatment of breast cancer from the 1970s onwards. It discusses early studies on drugs like tamoxifen, chemotherapy regimens for metastatic and early-stage breast cancer, and landmark clinical trials establishing the efficacy of Herceptin for HER2-positive breast cancer. The HERA trial is described in more detail, which found that one and two years of adjuvant Herceptin significantly improved disease-free survival compared to observation alone in HER2-positive early breast cancer.
A Novel Immunohistochemical Signature with the Quantification of HER2 Predict...Premier Publishers
This study evaluated biomarkers that can predict response to neoadjuvant chemotherapy and anti-HER2 therapy in HER2-positive breast cancer patients. The researchers found:
1) HER2 score alone was a poor predictor of response, with an AUC of 0.719 for HER2 score 3+.
2) A novel immunohistochemical signature incorporating high HER2 score 3+, high Ki67, low ER, and no lymph node involvement had an improved AUC of 0.809 for predicting response.
3) Optimal cut-off values for HER2 score 3+ varied by subtype, with 21% for HER2-enriched tumors having the best balance of sensitivity and specificity for predicting response.
The utility of “blind” 131I treatments for differentiated thyroid cancer: an...Michael
This document reviews literature on the use of 131I "blind" therapy, which is 131I treatment for differentiated thyroid cancer patients who have a positive thyroglobulin level and negative radioiodine whole body scan. It summarizes several studies that evaluated treatment outcomes based on changes in thyroglobulin levels post-therapy. The studies found response rates varied, with partial response in about 60% of treated patients and complete response in only 3%, compared to 44.6% and 5.4% respectively in untreated patients. However, the document concludes that the current literature does not resolve the controversy due to limitations like small sample sizes and lack of standardization in evaluating outcomes. More comprehensive prospective studies are needed to properly assess the
This document discusses how to interpret a forest plot used in a meta-analysis. A forest plot visually displays the results of individual studies and the overall meta-analysis. It shows the odds or risk ratio for each study with confidence intervals, along with a diamond representing the combined results. The location of the diamond in relation to the line of no effect indicates whether the overall effect is statistically significant. Heterogeneity between studies is also assessed using the forest plot and quantitative measures.
This study evaluated the performance of three pneumonia severity scores - CURB-65, CRB-65, and CURB-age - in predicting 30-day mortality in 559 adult inpatients with community-acquired pneumonia. The study found that CURB-age stratified patients into risk groups that were most closely associated with mortality outcomes. Specifically, CURB-age identified more low-risk patients who had lower mortality than CRB-65, and sorted more patients who died within 30 days into the high-risk group compared to the other scores. Analysis of receiver operating characteristics further indicated CURB-age had better ability to predict 30-day mortality compared to the other scores. The study concludes CURB-age may provide
1. A randomized trial compared restrictive (transfuse if Hb <7 g/dL) vs liberal (transfuse if Hb <9 g/dL) transfusion strategies in critically ill cancer patients with septic shock.
2. At 28 days, all-cause mortality was not significantly different between groups. However, at 90 days mortality was significantly higher in the restrictive group.
3. Secondary outcomes including ventilation, renal replacement therapy, inotropes, and length of stay showed no significant differences.
4. The results suggest a liberal transfusion strategy may be preferable for critically ill cancer patients with septic shock, as a restrictive strategy was associated with higher 90-day mortality.
Concurrent weekly single cisplatin vs triweekly cisplatin aloneHarihar Nath Tiwari
This document summarizes a meta-analysis comparing weekly vs triweekly cisplatin chemotherapy with radiotherapy for locally advanced cervical cancer. The analysis found no significant difference in 5-year overall survival or distant recurrence rates between the two regimens. However, the triweekly regimen was associated with higher treatment compliance and a higher risk of leucopenia as an acute adverse effect. In conclusion, triweekly cisplatin appeared superior for local recurrence and treatment compliance.
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Mina Max
This meta-analysis examined 12 randomized controlled trials involving 6,844 patients with advanced non-small cell lung cancer (NSCLC). The analysis compared chemotherapy with or without gefitinib. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The meta-analysis found that gefitinib therapy significantly improved PFS compared to chemotherapy alone, but only modestly improved OS and this difference was not statistically significant. Gefitinib therapy was associated with higher objective response rates. The most common adverse events with gefitinib were rash, diarrhea, and dry skin.
This document summarizes key milestones in the treatment of breast cancer from the 1970s onwards. It discusses early studies on drugs like tamoxifen, chemotherapy regimens for metastatic and early-stage breast cancer, and landmark clinical trials establishing the efficacy of Herceptin for HER2-positive breast cancer. The HERA trial is described in more detail, which found that one and two years of adjuvant Herceptin significantly improved disease-free survival compared to observation alone in HER2-positive early breast cancer.
A Novel Immunohistochemical Signature with the Quantification of HER2 Predict...Premier Publishers
This study evaluated biomarkers that can predict response to neoadjuvant chemotherapy and anti-HER2 therapy in HER2-positive breast cancer patients. The researchers found:
1) HER2 score alone was a poor predictor of response, with an AUC of 0.719 for HER2 score 3+.
2) A novel immunohistochemical signature incorporating high HER2 score 3+, high Ki67, low ER, and no lymph node involvement had an improved AUC of 0.809 for predicting response.
3) Optimal cut-off values for HER2 score 3+ varied by subtype, with 21% for HER2-enriched tumors having the best balance of sensitivity and specificity for predicting response.
The utility of “blind” 131I treatments for differentiated thyroid cancer: an...Michael
This document reviews literature on the use of 131I "blind" therapy, which is 131I treatment for differentiated thyroid cancer patients who have a positive thyroglobulin level and negative radioiodine whole body scan. It summarizes several studies that evaluated treatment outcomes based on changes in thyroglobulin levels post-therapy. The studies found response rates varied, with partial response in about 60% of treated patients and complete response in only 3%, compared to 44.6% and 5.4% respectively in untreated patients. However, the document concludes that the current literature does not resolve the controversy due to limitations like small sample sizes and lack of standardization in evaluating outcomes. More comprehensive prospective studies are needed to properly assess the
This document discusses how to interpret a forest plot used in a meta-analysis. A forest plot visually displays the results of individual studies and the overall meta-analysis. It shows the odds or risk ratio for each study with confidence intervals, along with a diamond representing the combined results. The location of the diamond in relation to the line of no effect indicates whether the overall effect is statistically significant. Heterogeneity between studies is also assessed using the forest plot and quantitative measures.
This study evaluated the performance of three pneumonia severity scores - CURB-65, CRB-65, and CURB-age - in predicting 30-day mortality in 559 adult inpatients with community-acquired pneumonia. The study found that CURB-age stratified patients into risk groups that were most closely associated with mortality outcomes. Specifically, CURB-age identified more low-risk patients who had lower mortality than CRB-65, and sorted more patients who died within 30 days into the high-risk group compared to the other scores. Analysis of receiver operating characteristics further indicated CURB-age had better ability to predict 30-day mortality compared to the other scores. The study concludes CURB-age may provide
Docetaxel Versus Docetaxel/Cisplatin in NSCLCJames Hilbert
This study compared docetaxel alone versus docetaxel plus cisplatin as frontline treatment for advanced non-small cell lung cancer. 302 patients were randomly assigned to receive either docetaxel alone (146 patients) or the docetaxel/cisplatin combination (156 patients). The overall response rate was significantly higher for the combination at 36% versus 18% for docetaxel alone. However, median survival time, time to disease progression, and 1-year survival rates were similar between the two groups. Toxicity was higher with the combination therapy. Both regimens showed similar effectiveness in terms of survival, though the combination resulted in a higher response rate and more toxicity.
British Medical Journal study on Oral ContraceptivesHarvey Diaz
This study analyzed mortality data from over 46,000 women in the Royal College of General Practitioners' Oral Contraception Study, which began in 1968. The study found that ever users of oral contraceptives had a 12% lower risk of death from any cause compared to never users. Ever users also had lower risks of death from cancers, circulatory diseases, and other specific causes. No clear association was found between duration of oral contraceptive use and overall mortality risk, though some disease-specific relationships were seen.
LCS101 (Protectival) Research Pubclications Abstractsyellowman
This document contains abstracts from multiple research publications on the botanical formula LCS101 and its potential effects in cancer treatment and reducing chemotherapy side effects. One study found LCS101 significantly reduced anemia, leukopenia, and neutropenia in breast cancer patients undergoing chemotherapy compared to a placebo. Another study found LCS101 selectively inhibited the growth of breast, colon, and prostate cancer cell lines while having no effect on normal cells. A third study found LCS101 increased the anticancer effects of doxorubicin and 5-FU on breast cancer cells but protected normal cells from chemotherapy-induced death.
Seven type 1 diabetes patients who received islet transplants under the Edmonton Protocol were followed for up to 12 years as part of the EXIIST study. All seven patients demonstrated continued islet function for over 10 years as measured by C-peptide levels. While the rate of insulin independence was low, with only two patients remaining insulin independent at the end of the study, the Edmonton Protocol was found to be safe long-term with no cases of severe hypoglycemia, opportunistic infection, or lymphoma reported. However, patients did experience a progressive decline in C-peptide and C-peptide to glucose ratios over time, indicating a gradual loss of islet function.
This randomized European study evaluated the effect of prostate-specific antigen (PSA) screening on death from prostate cancer. Over 182,000 men aged 50-74 were randomly assigned to screening via PSA tests every 4 years or a control group without screening. After a median follow-up of 9 years, the rate of death from prostate cancer was 20% lower in the screened group compared to the control group. However, screening led to a high risk of overdiagnosis, with many more cases of prostate cancer diagnosed through screening but a small effect on mortality. 1410 men needed to be screened and 48 extra prostate cancer cases needed to be treated to prevent one death from prostate cancer.
CINV (chemotherapy induced nausea & vomiting)Mohamed Abdulla
This document discusses chemotherapy-induced nausea and vomiting (CINV). It provides background on the speaker's disclosures and affiliations. It then reviews the pathophysiology of CINV, risk factors, types of CINV, and the impact of inadequate CINV control on quality of life and treatment adherence. It discusses guidelines for preventing CINV and the efficacy of different antiemetic drugs, including 5-HT3 receptor antagonists, NK1 receptor antagonists, and steroids. It also reviews the evolution of CINV prevention over time with improved antiemetic regimens.
astragalus injection as an adjuvant treatment for colorectal cancer: a meta-a...LucyPi1
This document summarizes a meta-analysis that evaluated the efficacy and safety of Astragalus injection as an adjuvant treatment for colorectal cancer. Eight randomized controlled trials involving 583 patients were included. The analysis found that compared to Western medicine alone, Astragalus injection improved treatment efficacy, improved patient quality of life, reduced leukopenia, reduced neurotoxicity, and reduced nausea and vomiting. The quality of the included studies was acceptable. In conclusion, Astragalus injection can reduce toxicity and improve the efficacy of conventional Western medicine in treating colorectal cancer.
- Two strategies are used to manage patients with unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI): an early invasive strategy involving prompt coronary angiography and revascularization, or a conservative strategy using medical therapy and invasive procedures only for recurrent ischemia.
- A meta-analysis of 8 randomized controlled trials found that an early invasive strategy significantly reduced the composite of death, myocardial infarction, and rehospitalization for acute coronary syndrome compared to conservative care at 6 months follow-up in patients presenting with UA, but not in those with NSTEMI alone.
- From randomization to discharge, an early invasive strategy was associated with higher rates of the composite endpoint in both UA/N
This document summarizes two recent studies on prognostic biomarkers for hepatocellular carcinoma (HCC). The first study found that high levels of C-reactive protein (CRP), an inflammatory marker, predicts poor long-term survival for patients with HCC undergoing nonsurgical treatments. The second study found that low levels of CD4+ cytotoxic T lymphocytes (CTLs), part of the immune system, predicts poor outcomes and high recurrence rates for HCC patients. Both inflammatory and immunological markers may provide prognostic information to supplement current clinical staging systems for HCC. However, more research is still needed to validate the prognostic value of these biomarkers.
This study evaluated the efficacy and safety of lacosamide in treating diabetic neuropathic pain through an 18-week double-blind trial of 370 patients with doses of 200 mg/day, 400 mg/day, and 600 mg/day compared to a placebo. The 400 mg/day dose was found to significantly improve pain scores over the placebo and had the optimal balance of efficacy and side effects. Common side effects included dizziness, tremor and headache. While lacosamide showed potential for treating diabetic neuropathic pain, the study period was short and the 600 mg/day group had a high withdrawal rate due to adverse events.
Introduction: Biochemical recurrence after radical prostatectomy has been associated with Gleason pattern 5(GP5) and Prostatic
Specifi c Antigen (PSA) is a sensitive marker of relapse. Was analyzed the correlation between the Gleason score 7(group 2 e 3), pattern Gleason 5, biochemical recurrence and its correlation with other adverse histological findings. Material and Methods: Historic cohort comprising 219 patients, subjected to score 7 radical prostatectomy with acinar adenocarcinoma. and GP5 represents 5% or less of tumor size. Recurrence was determined as postoperative PSA less or equal 0.2/ ml in the second postprostatectomy assessment. Were considered as signifi cant value of p < or equal to 0,005. All statistical analysis were conducted using the SPSS (SPSS Inc: released 2009, version 18.0, Chicago, IL, USA).
This article reviews literature on the use of cladribine in first line and relapsed hairy cell leukemia (HCL) and hairy cell leukemia variant (HCLv). Cladribine induces high complete response rates of 72-94% in first line treatment of HCL, regardless of prior treatment. It is also effective in relapsed HCL, achieving complete response rates of 44-76% in second line and 20-66% in third line. Response durations are longer in patients who achieve a complete versus partial response. Cladribine has been shown to extend overall survival in both first line and relapsed HCL.
Sample Work of an Meta-Analysis | Hire a Meta-Analysis Expert: Pubrica.comPubrica
Pubrica has a broad experience in all aspects of Scientific Medical Writing, Editing, and Publishing. A global leader in comprehensive manuscript publication support service for academic and scientific journals, We provide a wide range of services that include Scientific medical research writing, Clinical data analysis, Literature review, Meta-analysis, medical Communication and medico-marketing solutions to healthcare/pharmaceutical/food and beverage companies.
Find freelance Meta-Analysis professionals, consultants, freelancers and get your project done - https://bit.ly/30V8QUK
Why Pubrica:
When you order our services, we promise you the following – Plagiarism free, always on Time, outstanding customer support, written to Standard, Unlimited Revisions support and High-quality Subject Matter Experts.
Contact us:
Web: https://pubrica.com/
Blog: https://pubrica.com/academy/
Email: sales@pubrica.com
WhatsApp : +91 9884350006
United Kingdom : +44-1143520021
1) The document examines soluble epidermal growth factor receptor (sEGFR) levels in 308 advanced non-small cell lung cancer (NSCLC) patients and 109 healthy controls.
2) sEGFR levels were significantly lower in NSCLC patients compared to controls, however sEGFR alone was not a strong biomarker to distinguish patients from controls due to low sensitivity.
3) Lower sEGFR levels in patients correlated with poorer overall survival, suggesting sEGFR may be a useful prognostic biomarker in NSCLC. Further large-scale prospective studies are needed to validate its predictive value.
This document reviews treatments for neuroendocrine tumors (NETs), including peptide receptor radionuclide therapy (PRRT). It summarizes the evidence for various NET treatment options such as surgery, somatostatin analogs, PRRT, chemotherapy, and targeted therapies. It also provides an overview of a PRRT treatment day and integrates PRRT with other NET therapies. Clinical trial data is presented demonstrating the efficacy of PRRT and targeted therapies such as everolimus and sunitinib in extending progression-free survival for NETs. The conclusion emphasizes treating NETs only when necessary and considering surgery first followed by somatostatin analogs, PRRT, intra-arterial therapies,
1. The document analyzes the pathogenesis of lung adenocarcinoma in relation to current treatment guidelines and future developments. It finds that genomic analysis has identified recurrent dysregulation of the MAPK and PI3K/mTOR pathways, which drive cell cycle progression and pathogenesis.
2. Current targeted therapies against EGFR and PD-L1 have improved survival rates compared to non-targeted therapies, but an underappreciation of copy number alterations may be limiting progress. Future treatments are exploring targets like HER-2, KRAS, and CDK4/6 inhibitors.
3. While progress has been made, rapid further advances are still needed due to poor survival rates and a lack of defined patient cohorts
This document contains 4 photos shared under various Creative Commons licenses on Flickr. The photos depict nature scenes and were uploaded by different photographers for non-commercial reuse and sharing on other platforms with attribution.
Docetaxel Versus Docetaxel/Cisplatin in NSCLCJames Hilbert
This study compared docetaxel alone versus docetaxel plus cisplatin as frontline treatment for advanced non-small cell lung cancer. 302 patients were randomly assigned to receive either docetaxel alone (146 patients) or the docetaxel/cisplatin combination (156 patients). The overall response rate was significantly higher for the combination at 36% versus 18% for docetaxel alone. However, median survival time, time to disease progression, and 1-year survival rates were similar between the two groups. Toxicity was higher with the combination therapy. Both regimens showed similar effectiveness in terms of survival, though the combination resulted in a higher response rate and more toxicity.
British Medical Journal study on Oral ContraceptivesHarvey Diaz
This study analyzed mortality data from over 46,000 women in the Royal College of General Practitioners' Oral Contraception Study, which began in 1968. The study found that ever users of oral contraceptives had a 12% lower risk of death from any cause compared to never users. Ever users also had lower risks of death from cancers, circulatory diseases, and other specific causes. No clear association was found between duration of oral contraceptive use and overall mortality risk, though some disease-specific relationships were seen.
LCS101 (Protectival) Research Pubclications Abstractsyellowman
This document contains abstracts from multiple research publications on the botanical formula LCS101 and its potential effects in cancer treatment and reducing chemotherapy side effects. One study found LCS101 significantly reduced anemia, leukopenia, and neutropenia in breast cancer patients undergoing chemotherapy compared to a placebo. Another study found LCS101 selectively inhibited the growth of breast, colon, and prostate cancer cell lines while having no effect on normal cells. A third study found LCS101 increased the anticancer effects of doxorubicin and 5-FU on breast cancer cells but protected normal cells from chemotherapy-induced death.
Seven type 1 diabetes patients who received islet transplants under the Edmonton Protocol were followed for up to 12 years as part of the EXIIST study. All seven patients demonstrated continued islet function for over 10 years as measured by C-peptide levels. While the rate of insulin independence was low, with only two patients remaining insulin independent at the end of the study, the Edmonton Protocol was found to be safe long-term with no cases of severe hypoglycemia, opportunistic infection, or lymphoma reported. However, patients did experience a progressive decline in C-peptide and C-peptide to glucose ratios over time, indicating a gradual loss of islet function.
This randomized European study evaluated the effect of prostate-specific antigen (PSA) screening on death from prostate cancer. Over 182,000 men aged 50-74 were randomly assigned to screening via PSA tests every 4 years or a control group without screening. After a median follow-up of 9 years, the rate of death from prostate cancer was 20% lower in the screened group compared to the control group. However, screening led to a high risk of overdiagnosis, with many more cases of prostate cancer diagnosed through screening but a small effect on mortality. 1410 men needed to be screened and 48 extra prostate cancer cases needed to be treated to prevent one death from prostate cancer.
CINV (chemotherapy induced nausea & vomiting)Mohamed Abdulla
This document discusses chemotherapy-induced nausea and vomiting (CINV). It provides background on the speaker's disclosures and affiliations. It then reviews the pathophysiology of CINV, risk factors, types of CINV, and the impact of inadequate CINV control on quality of life and treatment adherence. It discusses guidelines for preventing CINV and the efficacy of different antiemetic drugs, including 5-HT3 receptor antagonists, NK1 receptor antagonists, and steroids. It also reviews the evolution of CINV prevention over time with improved antiemetic regimens.
astragalus injection as an adjuvant treatment for colorectal cancer: a meta-a...LucyPi1
This document summarizes a meta-analysis that evaluated the efficacy and safety of Astragalus injection as an adjuvant treatment for colorectal cancer. Eight randomized controlled trials involving 583 patients were included. The analysis found that compared to Western medicine alone, Astragalus injection improved treatment efficacy, improved patient quality of life, reduced leukopenia, reduced neurotoxicity, and reduced nausea and vomiting. The quality of the included studies was acceptable. In conclusion, Astragalus injection can reduce toxicity and improve the efficacy of conventional Western medicine in treating colorectal cancer.
- Two strategies are used to manage patients with unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI): an early invasive strategy involving prompt coronary angiography and revascularization, or a conservative strategy using medical therapy and invasive procedures only for recurrent ischemia.
- A meta-analysis of 8 randomized controlled trials found that an early invasive strategy significantly reduced the composite of death, myocardial infarction, and rehospitalization for acute coronary syndrome compared to conservative care at 6 months follow-up in patients presenting with UA, but not in those with NSTEMI alone.
- From randomization to discharge, an early invasive strategy was associated with higher rates of the composite endpoint in both UA/N
This document summarizes two recent studies on prognostic biomarkers for hepatocellular carcinoma (HCC). The first study found that high levels of C-reactive protein (CRP), an inflammatory marker, predicts poor long-term survival for patients with HCC undergoing nonsurgical treatments. The second study found that low levels of CD4+ cytotoxic T lymphocytes (CTLs), part of the immune system, predicts poor outcomes and high recurrence rates for HCC patients. Both inflammatory and immunological markers may provide prognostic information to supplement current clinical staging systems for HCC. However, more research is still needed to validate the prognostic value of these biomarkers.
This study evaluated the efficacy and safety of lacosamide in treating diabetic neuropathic pain through an 18-week double-blind trial of 370 patients with doses of 200 mg/day, 400 mg/day, and 600 mg/day compared to a placebo. The 400 mg/day dose was found to significantly improve pain scores over the placebo and had the optimal balance of efficacy and side effects. Common side effects included dizziness, tremor and headache. While lacosamide showed potential for treating diabetic neuropathic pain, the study period was short and the 600 mg/day group had a high withdrawal rate due to adverse events.
Introduction: Biochemical recurrence after radical prostatectomy has been associated with Gleason pattern 5(GP5) and Prostatic
Specifi c Antigen (PSA) is a sensitive marker of relapse. Was analyzed the correlation between the Gleason score 7(group 2 e 3), pattern Gleason 5, biochemical recurrence and its correlation with other adverse histological findings. Material and Methods: Historic cohort comprising 219 patients, subjected to score 7 radical prostatectomy with acinar adenocarcinoma. and GP5 represents 5% or less of tumor size. Recurrence was determined as postoperative PSA less or equal 0.2/ ml in the second postprostatectomy assessment. Were considered as signifi cant value of p < or equal to 0,005. All statistical analysis were conducted using the SPSS (SPSS Inc: released 2009, version 18.0, Chicago, IL, USA).
This article reviews literature on the use of cladribine in first line and relapsed hairy cell leukemia (HCL) and hairy cell leukemia variant (HCLv). Cladribine induces high complete response rates of 72-94% in first line treatment of HCL, regardless of prior treatment. It is also effective in relapsed HCL, achieving complete response rates of 44-76% in second line and 20-66% in third line. Response durations are longer in patients who achieve a complete versus partial response. Cladribine has been shown to extend overall survival in both first line and relapsed HCL.
Sample Work of an Meta-Analysis | Hire a Meta-Analysis Expert: Pubrica.comPubrica
Pubrica has a broad experience in all aspects of Scientific Medical Writing, Editing, and Publishing. A global leader in comprehensive manuscript publication support service for academic and scientific journals, We provide a wide range of services that include Scientific medical research writing, Clinical data analysis, Literature review, Meta-analysis, medical Communication and medico-marketing solutions to healthcare/pharmaceutical/food and beverage companies.
Find freelance Meta-Analysis professionals, consultants, freelancers and get your project done - https://bit.ly/30V8QUK
Why Pubrica:
When you order our services, we promise you the following – Plagiarism free, always on Time, outstanding customer support, written to Standard, Unlimited Revisions support and High-quality Subject Matter Experts.
Contact us:
Web: https://pubrica.com/
Blog: https://pubrica.com/academy/
Email: sales@pubrica.com
WhatsApp : +91 9884350006
United Kingdom : +44-1143520021
1) The document examines soluble epidermal growth factor receptor (sEGFR) levels in 308 advanced non-small cell lung cancer (NSCLC) patients and 109 healthy controls.
2) sEGFR levels were significantly lower in NSCLC patients compared to controls, however sEGFR alone was not a strong biomarker to distinguish patients from controls due to low sensitivity.
3) Lower sEGFR levels in patients correlated with poorer overall survival, suggesting sEGFR may be a useful prognostic biomarker in NSCLC. Further large-scale prospective studies are needed to validate its predictive value.
This document reviews treatments for neuroendocrine tumors (NETs), including peptide receptor radionuclide therapy (PRRT). It summarizes the evidence for various NET treatment options such as surgery, somatostatin analogs, PRRT, chemotherapy, and targeted therapies. It also provides an overview of a PRRT treatment day and integrates PRRT with other NET therapies. Clinical trial data is presented demonstrating the efficacy of PRRT and targeted therapies such as everolimus and sunitinib in extending progression-free survival for NETs. The conclusion emphasizes treating NETs only when necessary and considering surgery first followed by somatostatin analogs, PRRT, intra-arterial therapies,
1. The document analyzes the pathogenesis of lung adenocarcinoma in relation to current treatment guidelines and future developments. It finds that genomic analysis has identified recurrent dysregulation of the MAPK and PI3K/mTOR pathways, which drive cell cycle progression and pathogenesis.
2. Current targeted therapies against EGFR and PD-L1 have improved survival rates compared to non-targeted therapies, but an underappreciation of copy number alterations may be limiting progress. Future treatments are exploring targets like HER-2, KRAS, and CDK4/6 inhibitors.
3. While progress has been made, rapid further advances are still needed due to poor survival rates and a lack of defined patient cohorts
This document contains 4 photos shared under various Creative Commons licenses on Flickr. The photos depict nature scenes and were uploaded by different photographers for non-commercial reuse and sharing on other platforms with attribution.
Human Interaction Keynote Brushfire Interactive July 2015Ryan Smeets
AZIMA Keynote from July 23, 2015. Ryan Smeets, Director of Client Strategy at Brushfire Interactive lead a discussion on the topic of UX/UI: Design for Human Interaction
Undang-undang ini mengatur tentang hak cipta dan hak terkait di Indonesia. Hak cipta merupakan hak eksklusif yang terdiri atas hak moral dan hak ekonomi bagi pencipta atau pemegang hak cipta untuk mendapatkan manfaat ekonomi atas ciptaannya. Undang-undang ini juga mengatur tentang hak terkait yang dimiliki pelaku pertunjukan, produser fonogram, dan lembaga penyiaran.
This document is a resume for Jake Johnston that summarizes his career and qualifications. It outlines his education including a BA in Economics from University of Western Ontario and some business courses. His work experience includes roles in banking, hotels, and retail with a focus on sales, customer service, and training. He held several top ranking positions and has a proven track record of exceeding sales goals.
The V320i thermal transfer printer is the highest performing and most cost effective coding solution for flexible packaging and labels. It offers industry-leading printing speeds of up to 1400mm/sec, versatility in printing modes, and the lowest total cost of ownership in the industry due to features that reduce ribbon usage by up to 60% without compromising print quality.
This short document promotes the creation of presentations using Haiku Deck, an online presentation tool. It displays photos from three photographers who have used Haiku Deck and encourages the reader to get started making their own Haiku Deck presentation by uploading it to SlideShare.
This document provides information on various music and youth entertainment channels in India, including their popular shows and brand integrations. It discusses channels like MTV India, Channel V, and Bindass. For each channel, it summarizes their flagship shows, target demographics, and integration strategies with brands. It also provides the latest updates on initiatives by these channels like partnerships and format changes of popular shows.
Este documento presenta información sobre hipertensión arterial, incluyendo su definición, factores de riesgo, datos epidemiológicos, evaluación clínica, estudios de laboratorio, clasificación y tratamiento actual. Explica diferentes tipos como hipertensión sistólica aislada, de bata blanca, refractaria y maligna. También discute causas comunes de hipertensión refractaria y prevalencia en Cuba, así como requisitos y combinaciones sinérgicas para el tratamiento farmacológico.
The document provides information about resume samples, tips, cover letters, and interview questions for an inventory associate position. It lists several useful resources from resume123.org, including resume samples, tips for writing effective resumes, cover letter samples, interview questions and answers, secrets to winning job interviews, types of interview questions, job interview checklists, and thank you letter samples. It also provides information on related career fields and job title levels that the resume samples could be applicable for.
This short document promotes creating presentations on SlideShare using Haiku Deck. It includes photos from stock photo sites to illustrate the point and encourages the reader to get started making their own Haiku Deck presentation on SlideShare.
The document provides information about resume samples, tips, cover letters, and interview questions for records clerk positions. It lists several useful resources from resume123.org, including free resume samples, tips for writing effective resumes, cover letter samples, and ebooks with interview questions, secrets to winning interviews, and tips for job searching. The document also provides information on fields and job levels that the resume samples could be applicable for.
This document summarizes the community involvement and financial strength of a MassMutual agency. It highlights that the agency is committed to helping clients make good financial decisions and has a long-standing commitment to the communities it serves through philanthropic donations and volunteer work. The agency leverages MassMutual's over 160 years of experience and financial strength to serve over 13,000 clients with $4.3 billion in life insurance coverage.
Darriell Givens has over 10 years of experience in design and branding. She has a degree in Digital Arts and Design from Full Sail University. Her experience includes working on political campaigns and creating branding assets for various companies. She is currently a freelance designer based in Miami working with local organizations. Her goal is to inspire creativity through her design work and staying connected to her community.
34320294 jak inhibitors more than just glucocorticoids (1)EVELIN LÁZARO
This editorial discusses recent trials investigating immunomodulatory therapies for COVID-19. It finds that treatment with glucocorticoids (dexamethasone) and JAK inhibitors reduces mortality in hospitalized patients receiving supplemental oxygen or ventilation. Combining JAK inhibitors with glucocorticoids may widen the window of benefit compared to either treatment alone. The editorial concludes that anti-inflammatory therapies reduce mortality in COVID-19 patients with moderate to severe disease, and that JAK inhibitors are a particularly promising option due to their oral administration, safety profile, and potential for combination with glucocorticoids.
1) A study analyzed data from 687 patients with triple negative breast cancer who received surgery and adjuvant chemotherapy. The study found that as the time between surgery and starting chemotherapy increased, both 10-year disease-free survival and 10-year overall survival decreased.
2) Patients who started chemotherapy within 30 days of surgery had the best outcomes, with 10-year disease-free survival of 81.4% and 10-year overall survival of 82%.
3) Delaying the start of adjuvant chemotherapy by more than 90 days after surgery was associated with significantly worse survival outcomes.
Safety and clinical activity of pembrolizumab for treatmentMarwa EL-Sayed
Pembrolizumab is a humanized monoclonal antibody that targets the PD-1 receptor. This study evaluated the safety and efficacy of pembrolizumab in 104 patients with recurrent or metastatic squamous cell carcinoma of the head and neck. The results showed that pembrolizumab had a manageable safety profile, with 63% of patients experiencing drug-related adverse events mostly grade 1-2. Pembrolizumab also demonstrated promising anti-tumor activity with an 18% overall response rate. Progression-free survival was 13 months. This study provides evidence that pembrolizumab is a potential new treatment option for this patient population.
The study evaluated dual HER2 blockade with lapatinib plus trastuzumab plus an aromatase inhibitor compared to trastuzumab plus an aromatase inhibitor or lapatinib plus an aromatase inhibitor in patients with HER2-positive, hormone receptor-positive metastatic breast cancer. 355 patients were randomly assigned to one of the three treatment arms. The results showed that progression-free survival was significantly longer in the lapatinib plus trastuzumab plus aromatase inhibitor arm compared to the trastuzumab plus aromatase inhibitor arm, with overall response and clinical benefit rates also being higher. Overall survival data were immature but trended in favor of the lapatinib plus trastuzumab arm. The most common
Austin Journal of Clinical Cardiology is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of cardiology and angiology. The aim of the journal is to provide a forum for cardiologists, researchers, physicians, and other health professionals to find most recent advances in the areas of cardiology and cardiovascular diseases.
Austin Journal of Clinical Cardiology accepts original research articles, review articles, case reports, clinical images and rapid communication on all the aspects of cardiology and circulatory system.
Austin Journal of Clinical Cardiology strongly supports the scientific upgradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Austin Journal of Clinical Cardiology is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of cardiology and angiology
- Renal cell carcinoma (RCC) incidence has increased in recent years, with 20-50% of localized cases progressing to metastatic cancer.
- Several risk stratification models (UISS, SSIGN, Leibovich) are used to predict survival and guide surveillance and treatment eligibility.
- Early adjuvant trials of VEGF TKIs like sunitinib and sorafenib showed minimal improvement in disease-free survival at significant cost of toxicity.
- The KEYNOTE-564 trial showed significant improvement in disease-free survival for high-risk RCC patients treated with adjuvant pembrolizumab compared to placebo.
The effect of long-term traditional Chinese medicine treatment on disease-fre...LucyPi1
Abstract Objective: Traditional Chinese medicine (TCM) has been extensively used as one of popular alternative therapies for several cancers. However, it remains unclear whether TCM treatment is associated with longer survival in lung cancer patients. In this study, we explored the effect of long-term TCM treatment on patients with different stages of lung cancer. Methods: All information of lung cancer patients with stage I-III disease from January 2007 to September 2015 was collected for this retrospective cohort study. Those who were treated with TCM after surgery were divided into TCM group and the others were into the non-TCM group (control group). All patients were regularly followed up by clinic appointment or phone, and all survival data were collected from databases after the last follow-up in October 2017. Results: A total of 575 patients were included in this study, with 299 patients in the TCM group and 276 in the control group. For all patients, 5-year disease-free survival (DFS) was 62.2% in TCM group and 42.1% in the control group, and 6-year DFSs were 51.8% and 35.4%, respectively (HR = 0.51, 95% CI: 0.40 to 0.66, log-rank P ≤ 0.001). For patients with stage I, 5-year DFSs were 83.7% (TCM group) and 57.5% (control group) and 6-year DFSs were 73.7% and 51.9%, respectively (HR = 0.30, 95% CI: 0.18 to 0.50, log-rank P ≤ 0.001). For patients with stage II in the TCM group and the control group, 5-year DFSs were 59.4% and 17.6% and 6-year DFSs were 44.7% and 17.6%, respectively (HR = 0.31, 95% CI: 0.19 to 0.52, log-rank P ≤ 0.001), and for patients with stage III, 5-year and 6-year DFSs in the TCM group were 18.7% and 12.5% compared with 28.4% and 20.3% in the control group (HR = 1.06, 95% CI: 0.72 to 1.56, log-rank P = 0.76). Conclusions: This study demonstrated that long-term TCM treatment as an adjuvant therapy is able to improve the DFS of postoperative stage I-III lung cancer patients, especially in patients with stage I and II disease. However, these observational findings need being validated by large sample randomized controlled trials.
This document discusses clinical proof-of-concept (POC) trials in drug development. It defines POC as establishing whether a drug is reasonably likely to succeed based on early evidence of safety and efficacy. The document outlines goals of POC trials, decision criteria used, and strategies to improve probability of success such as better patient selection using biomarkers. It provides examples of oncology POC trials and discusses practical considerations for using patient selection approaches.
Secondary Malignancy after Treatment of Prostate Cancer. Radical Prostatectom...asclepiuspdfs
Background: This study aims to determine whether the treatment of locally confined prostate cancer (PCa) with external radiotherapy (EBRT) increases the risk to develop secondary malignancies (SM) compared to radical prostatectomy (RPE). Materials and Methods: Data from patients who were treated curatively with RPE or EBRT from 2010 to 2018 and who did not have distant metastases, previous malignancy, or previous treatment with radiotherapy or chemotherapy at the time of diagnosis were reviewed to determine the incidence of SM over a median follow-up period of 47 months (range 12–96 months). Regression models were used to correlate the clinicopathological factors with the incidence of SM.
Meta-Analysis of Traditional Chinese Medicine Injection Combined with Paclita...semualkaira
To investigate the effect of traditional Chinese medicine injection combined with paclitaxel, cisplatin or carboplatin chemotherapy regimen (TP Chemotherapy Regimen) on lung cancer.
Meta-Analysis of Traditional Chinese Medicine Injection Combined with Paclita...semualkaira
To investigate the effect of traditional Chinese medicine injection combined with paclitaxel, cisplatin or carboplatin chemotherapy regimen (TP Chemotherapy Regimen) on lung cancer.
Clinical trials follow a phased process to evaluate new treatments. Phase I trials test safety in small groups. Phase II trials assess efficacy in larger groups. Phase III trials compare new treatments head-to-head with standard treatments in large randomized controlled trials. Higher levels of evidence come from systematic reviews and meta-analyses of multiple randomized controlled trials, while lower levels of evidence derive from expert opinions and single descriptive studies.
Association between genomic recurrence risk and well-being among breast cance...Enrique Moreno Gonzalez
Gene expression profiling (GEP) is increasingly used in the rapidly evolving field of personalized medicine. We sought to evaluate the association between GEP-assessed of breast cancer recurrence risk and patients’ well-being.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...JohnJulie1
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...EditorSara
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...EditorSara
This study aimed to investigate the correlation between the expression of P4HB and GRP78 proteins and their prognostic value in gastric cancer. The study found that P4HB protein expression was positively correlated with GRP78 protein expression in gastric cancer tissue samples. High expression of either P4HB or GRP78 alone, or co-expression of both, was associated with poorer overall survival in patients. When considering postoperative adjuvant chemotherapy, high co-expression of P4HB and GRP78 only represented an unfavorable prognosis in patients who received chemotherapy. A prognostic nomogram incorporating P4HB and GRP78 expression and other factors was developed and found to have better predictive performance than the TNM staging system.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...NainaAnon
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
2. 2
ABSTRACT
Background: Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is
associated with higher chemotherapy relative dose intensity, which may lead to
improved outcomes; however, the association between G-CSF primary prophylaxis and
overall survival (OS) is not well characterized. This study assessed the effect of G-CSF
primary prophylaxis on patient outcomes in randomized, controlled, registrational clinical
trials of filgrastim and pegfilgrastim.
Patients and methods: Three placebo-controlled and two noninferiority clinical trials of
filgrastim and/or pegfilgrastim in patients receiving myelosuppressive chemotherapy for
lung, breast, or colorectal cancer were included. Median OS, 6- and 12-month survival
rates, and hazard ratios (HRs; unadjusted Cox model with 95% confidence intervals
[CIs]) were estimated for patients receiving ≥1 dose of filgrastim, pegfilgrastim, or
placebo. Comparisons were based on a log-rank test. A fixed-effect meta-analysis
assessed the effect of primary prophylaxis with filgrastim/pegfilgrastim on OS in the
placebo-controlled trials.
Results: In patients with lung cancer receiving filgrastim versus placebo, median OS
was 14.1 versus 11.1 months (HR, 0.81; 95% CI, 0.48–1.35; P=0.412); in patients who
crossed over to filgrastim from placebo after cycle 1, median OS was 16.9 months (HR,
0.75; 95% CI, 0.43–1.28; P=0.286). Median OS was inestimable in at least one
treatment arm in the other studies because of the small number of OS events. Where
estimable, 6- and 12-month survival rates were generally greater among patients
receiving filgrastim/pegfilgrastim versus placebo. In the meta-analysis of placebo-
3. 3
controlled studies comparing G-CSF primary prophylaxis with placebo in the as-treated
analysis sets, the HR (95% CI) for OS was 0.77 (0.58–1.03).
Conclusions: In this retrospective analysis, OS point estimates were greater among
patients receiving filgrastim versus placebo, but the differences were not statistically
significant. Further studies evaluating patient outcomes with G-CSF prophylaxis are
warranted.
Abstract word count: 287 (limit, 300)
Clinical trial registration: NCT00035594, NCT00094809
Keywords: pegfilgrastim, filgrastim, G-CSF, overall survival, neutropenia
Key message: In this analysis of registrational clinical trials of filgrastim and
pegfilgrastim, patients with cancer receiving myelosuppressive chemotherapy with
prophylactic G-CSF support had greater OS point estimates compared with placebo, and
the hazard ratio for OS was <1 in a meta-analysis of the placebo-controlled studies in
favor of G-CSF vs placebo. The results were not statistically significant.
4. 4
Introduction
Severe neutropenia (SN) and febrile neutropenia (FN) are dose-limiting toxicities of
myelosuppressive chemotherapy that may lead to chemotherapy dose delays or dose
reductions [1-3]. Prophylactic granulocyte colony-stimulating factor (G-CSF) therapy has
been shown to reduce the incidence of SN and FN in patients receiving chemotherapy
for nonmyeloid malignancies and has been associated with increased chemotherapy
relative dose intensity (RDI) compared with the absence of G-CSF support [4-9].
Retrospective analyses of randomized controlled trials (RCTs) have shown an
association between higher chemotherapy RDI and improved outcomes in patients
receiving cytotoxic chemotherapy [10, 11]. A recent meta-analysis of RCTs assessing
G-CSF primary prophylaxis in patients receiving myelosuppressive chemotherapy
demonstrated a reduction in all-cause mortality among patients receiving G-CSF support
[12]; however, the effect of G-CSF primary prophylaxis on overall survival (OS) has not
been well characterized in clinical trials. This retrospective analysis assessed the effect
of G-CSF primary prophylaxis on OS in patients receiving myelosuppressive
chemotherapy and filgrastim, pegfilgrastim, or placebo in five registrational RCTs for
which outcome data were available [5-9].
Methods
Studies and patients
An overview of the five registrational RCTs is presented in Table 1. The placebo-
controlled trials were a phase 3 trial of filgrastim in small cell lung cancer (SCLC) [5], a
phase 3 trial of pegfilgrastim in breast cancer (NCT00035594) [6], and a phase 2 trial of
5. 5
pegfilgrastim in colorectal cancer (NCT00094809) [7]. Two phase 3 noninferiority trials
compared pegfilgrastim with filgrastim in breast cancer (referred to as noninferiority
study 1 [8] and noninferiority study 2 [9]).
Calculation of summary statistics for exposure to pegfilgrastim/filgrastim was based on
the total dose for each patient over four cycles of chemotherapy (pegfilgrastim dose =
single dose × 4; filgrastim dose = single dose × days of dosing × 4). Similarly, the
tabulation of the number of doses reflects the total number of doses received by a
patient in four cycles. For patients who crossed over from placebo to G-CSF after cycle
1, summary statistics for exposure and the total number of doses were calculated based
on a maximum of three cycles.
Meta-analysis of OS from Cox proportional hazard (PH) models in the three placebo-
controlled trials was performed using a fixed-effect model; no measurable heterogeneity
was detected (I2
= 0%). Results of the meta-analysis at the level of individual patient
data (IPD) with a stratified Cox PH model were identical.
Data collection and analysis
The original publications of the placebo-controlled registrational trials reported
OS/deaths for the intent-to-treat (ITT) analysis set. In this analysis, the treatment arms
for OS/deaths were determined by the treatment actually received (as-treated set).
Exposure to pegfilgrastim/filgrastim and OS are reported separately for patients who
crossed over from placebo to G-CSF according to study design. The meta-analysis of
the three placebo-controlled trials used the as-treated analysis sets.
6. 6
Incidence of severe neutropenia and febrile neutropenia
Severe neutropenia was defined as grade 3/4 neutropenia (absolute neutrophil count
[ANC] <1.0 × 109
cells/L) or grade 4 neutropenia (ANC <0.5 × 109
cells/L). Febrile
neutropenia was defined as a temperature ≥38.2ºC with ANC <1.0 × 109
cells/L [5, 7] or
ANC <0.5 × 109
cells/L [6, 8, 9] on the same day [5-9] or the day after [6, 7] completion
of chemotherapy. The incidence and duration of SN and FN were evaluated for the
safety analysis set in the placebo-controlled studies. Differences between the G-CSF
and placebo arms in the incidence of SN and FN were evaluated by calculating the
relative risk (RR), where RR <1.0 indicated a lower event rate for the G-CSF arm versus
the placebo arm; P values were calculated using the chi-square test. The incidence of
SN and FN was assessed only in cycle 1 because patients randomized to placebo in the
lung and breast cancer studies who developed FN could cross over after cycle 1 to
receive open-label filgrastim or pegfilgrastim, respectively [5, 6]. Blood collection for the
assessment of ANC was performed 3 days per week in the lung cancer study [5],
allowing reliable estimates of the duration of neutropenia. Because blood was collected
only once per week in the breast and colorectal cancer studies [6, 7], duration of
neutropenia could not be assessed.
Antibiotic use
Differences in intravenous and oral antibiotic use for any cause between the G-CSF and
placebo arms were evaluated by calculating RR, where RR <1.0 indicated a lower use
rate for the G-CSF arm relative to the placebo arm; P values were based on the chi-
square test. Deaths by extent of disease were summarized descriptively.
7. 7
Overall survival
Kaplan-Meier estimates of OS (the time from study day 1 until death) and 6- and 12-
month survival rates (where estimable) were compared between arms using an
unadjusted log-rank test. Maximum follow-up time on the phase 3 breast cancer trial [6]
was 159 days, insufficient to estimate 6- and 12-month survival. Median survival time
was not reached for the two noninferiority trials. Unadjusted Cox PH models were used
to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A fixed-effect,
study-level meta-analysis was performed to estimate OS among the three placebo-
controlled trials. In the absence of heterogeneity, the results from the IPD analysis
(stratified on study) were identical.
Results
Cycle 1 incidence of severe neutropenia and febrile neutropenia
In the ITT analysis sets of the three placebo-controlled studies, the incidence of grade
3/4 neutropenia in cycle 1 was significantly lower among patients receiving G-CSF
versus placebo (Table 2). The incidences of grade 3/4 and grade 4 neutropenia were
significantly lower among patients in the lung cancer study receiving filgrastim versus
placebo (P=0.0014 and P=0.0001, respectively), as was the incidence of FN (P<0.001).
Likewise, the incidences of grade 3/4 and grade 4 neutropenia were significantly lower
among patients in the breast cancer study receiving pegfilgrastim versus placebo (both
P<0.0001), as was the incidence of FN (P<0.001). In the colorectal cancer study, the
incidence of grade 3/4 neutropenia was significantly lower among patients receiving
pegfilgrastim versus placebo (P=0.0027).
8. 8
Cycle 1 antibiotic use
Oral and intravenous antibiotic use (any cause) in cycle 1 was significantly reduced
among patients in the lung cancer study receiving filgrastim versus placebo (P=0.0048)
and among patients in the breast cancer study receiving pegfilgrastim versus placebo
(P=0.0007; Table 2). The difference in antibiotic use in the colorectal cancer study,
however, was not statistically significant (P=0.580).
Exposure to G-CSF and chemotherapy
Across all studies, the median exposure (mg) to pegfilgrastim or filgrastim was similar
(Table 3). In the two placebo-controlled trials, in which crossover from placebo to G-
CSF was allowed by study design [5, 6], the median exposure (mg and number of
doses) was similar and consistent among patients receiving G-CSF for a total of four
cycles beginning in cycle 1 and patients who crossed over from placebo and received G-
CSF for a total of three cycles beginning in cycle 2. In the noninferiority studies [8, 9],
mean exposure was higher in pegfilgrastim treatment arms compared with filgrastim
treatment arms.
The studies included in this analysis reported limited information on chemotherapy RDI,
with no information on dose reductions or delays reported in the placebo-controlled lung
cancer study or the first noninferiority breast cancer study [5, 9]. In the placebo-
controlled trial in colorectal cancer [7], a nonsignificant difference in the incidence of
chemotherapy dose delays or reductions was observed between patients receiving
pegfilgrastim versus placebo (33.4% vs 45%; P=0.06). In the placebo-controlled trial in
breast cancer [6], 80% and 78% of patients in the pegfilgrastim and placebo groups,
respectively, received their planned chemotherapy dose on time; these results were
expected because patients who developed FN then crossed over to pegfilgrastim. The
9. 9
second noninferiority breast cancer study reported similar chemotherapy dose
administration between the filgrastim and pegfilgrastim arms, with 90% of patients
receiving chemotherapy according to the planned schedule [8].
Overall survival and 6- and 12-month survival
There were generally fewer OS events among patients receiving G-CSF versus placebo
in the placebo-controlled studies; there were generally fewer OS events among patients
receiving pegfilgrastim versus filgrastim in the noninferiority studies (Table 4; Figure 1).
In the lung cancer study, the point estimate for median OS was 3 months longer among
patients receiving filgrastim only versus placebo only, but the difference was not
statistically significant (P=0.412 for HR). Among patients in the placebo arm receiving
open-label filgrastim after cycle 1 as a result of FN, the point estimate for median OS
was almost 6 months longer versus placebo only, but the difference was not statistically
significant (P=0.286 for HR). In the other studies, median OS could not be estimated
because of the small number of OS events.
To evaluate the relationship between G-CSF primary prophylaxis and survival, a fixed
effect model meta-analysis of the placebo-controlled studies was performed. In the as-
treated analysis sets comparing G-CSF primary prophylaxis with placebo, the HR (95%
CI) for OS was 0.77 (0.58–1.03).
In the placebo-controlled studies, where estimable, 6- and 12-month survival rates were
generally higher among patients receiving G-CSF (beginning in cycle 1 or cycle 2)
versus placebo (Table 4). In the noninferiority studies, 6- and 12-month survival rates,
where estimable, were comparable among patients receiving pegfilgrastim versus
filgrastim.
10. 10
Discussion
Chemotherapy-induced FN can often result in chemotherapy dose delays or dose
reductions, which may result in reduced chemotherapy RDI and compromised outcomes
[13-16]. Meta-analyses and pooled analyses have provided some evidence of an
association between G-CSF primary prophylaxis and improved survival in patients
receiving myelosuppressive chemotherapy [4, 12, 17]. In this retrospective analysis of
RCTs of filgrastim and pegfilgrastim [5-7], patients receiving G-CSF primary prophylaxis
had greater median OS point estimates and greater 6- and 12-month survival rates
versus placebo, but the benefits were not statistically significant. Similar nonsignificant
increases in the median OS point estimate and 6- and 12-month survival rates were
seen among patients with SCLC who were randomized to placebo but then crossed over
to open-label filgrastim after experiencing FN during cycle 1. In the fixed-effect meta-
analysis of the placebo-controlled studies (Cox PH model with no heterogeneity), the HR
for OS was <1 in favor of G-CSF primary prophylaxis compared with placebo; although
the result was not statistically significant, it may be considered hypothesis generating.
In contrast with the original reports of the registrational studies [5-9], this analysis
assessed OS data from patients in the as-treated analysis data set rather than the ITT
data set to ensure that the OS estimate reflected the actual treatment received by
patients. Results of our survival analysis are consistent with those in previous reports [4,
12, 17, 18]. In a meta-analysis of RCTs (N=59), patients receiving G-CSF primary
prophylaxis with myelosuppressive chemotherapy had reduced mortality risk versus
patients without G-CSF support (RR, 0.93; P<0.001) [12]. In an earlier meta-analysis of
17 RCTs, patients receiving primary prophylaxis with filgrastim, pegfilgrastim, or
lenograstim had lower risk of infection-related mortality (RR, 0.55; P=0.018) and early
mortality during chemotherapy treatment (RR, 0.60; P=0.002) versus patients without G-
11. 11
CSF support [4]. Evidence of improved survival has also been observed with G-CSF
prophylaxis in patients receiving myelosuppressive chemotherapy for myeloid
malignancies [17, 18]. Notably, a higher 5-year survival rate was observed with primary
prophylaxis with filgrastim or lenograstim versus no prophylaxis in a subgroup of patients
with acute lymphoblastic leukemia (44% versus 27%; P=0.03) [17]. Additionally, patients
receiving filgrastim or pegfilgrastim prophylaxis during the first cycle (P=0.018) or any
cycle (P=0.04) of chemotherapy for acute myeloid leukemia survived longer than
patients who did not receive prophylaxis [18]. Collectively, our retrospective analysis
and these studies provide evidence that G-CSF primary prophylaxis may improve OS in
patients receiving myelosuppressive chemotherapy.
In all three placebo-controlled studies, exposure to G-CSF was generally similar
between active treatment arms, and the incidence of grade 3/4 neutropenia in cycle 1
was significantly lower among patients receiving G-CSF compared with those receiving
placebo. The incidences of grade 4 neutropenia, FN, and antibiotic use in cycle 1 were
also lower in the G-CSF arms of the placebo-controlled studies, but the differences were
not statistically significant in the colorectal cancer study. The apparent treatment effect
of G-CSF primary prophylaxis was likely reduced in the placebo-controlled SCLC [5] and
breast cancer [6] studies, which allowed patients in the placebo arm to cross over to
secondary prophylaxis with G-CSF after cycle 1 as a result of FN. This crossover design
limited the ability to evaluate the impact of G-CSF on survival outcomes in these trials.
This analysis had several limitations. First, the number of OS events was small, and the
studies were neither designed nor powered to assess OS [5-9]. Second, patients who
crossed over from the placebo arm to the G-CSF arm in cycle 2 did so after experiencing
FN in cycle 1 and cannot be assumed to have the same risk of FN as patients who
12. 12
remained on the assigned therapy. In the lung cancer study, OS in the placebo-only arm
may have been shortened by early deaths/withdrawals compared with the crossover arm
in which patients survived to receive subsequent therapy. Third, follow-up time was not
equivalent among the studies (60–240 days in the placebo-controlled breast cancer
study and noninferiority study 1 versus 900–1000 days in the other studies). Fourth, the
studies differed in the tumor types and chemotherapy regimens and in how and when
neutropenia was assessed. Lastly, because of limited availability of data, we were not
able to determine in this analysis if patients receiving G-CSF experienced fewer
chemotherapy dose delays or higher RDIs that may have correlated with improved
outcomes. Despite these limitations, many of which were likely to bias against the G-
CSF-containing arm, point estimates for OS were greater among patients receiving G-
CSF primary prophylaxis compared with placebo. However, the differences were not
statistically significant.
Current guidelines recommend initiating primary prophylaxis with G-CSF in patients at
high risk for FN in the first chemotherapy cycle or when needed for the on-time delivery
of full-dose chemotherapy [19-22]. Secondary prophylaxis is less desirable because
many patients may experience neutropenic complications before receiving G-CSF
support. Prospective assessment of the effects of G-CSF primary prophylaxis on long-
term outcomes in patients with cancer receiving myelosuppressive chemotherapy is
warranted.
13. 13
Acknowledgments
The authors acknowledge James Balwit, MS, and Benjamin Scott, PhD, whose work
was funded by Amgen Inc., for assistance in writing this manuscript.
Funding
This study was funded by Amgen Inc. There were no grants or applicable grant
numbers for this study.
Disclosures
GHL is the primary investigator on a research grant from Amgen Inc. to the Fred
Hutchinson Cancer Research Center. MR and PKM are employees of and own stock in
Amgen Inc. JC has served as a consultant for and has received research funding from
Amgen Inc.
14. 14
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Figure Legend
Figure 1. Kaplan-Meier curves for median overall survival in the safety analysis set
for (A) the phase 3 small cell lung cancer study, (B) the phase 3 breast
cancer study, (C) the phase 2 colorectal cancer study, (D) noninferiority
study 1 (phase 3 breast cancer), and (E) noninferiority study 2 (phase 3
breast cancer). Patients randomized to placebo were allowed to cross
over to receive open-label filgrastim (A) or pegfilgrastim (B) as a result of
febrile neutropenia during cycle 1. Note: The duration of follow-up differs
among the studies.
26. c
Includes all intravenous and oral antibiotic use.
d
RR <1.0 indicates a lower event rate for the G-CSF arm relative to the placebo arm.
e
P value based on the chi-square test.
27. Table 3. Exposure to Pegfilgrastim/Filgrastim and Baseline Disease Characteristics in the Safety Analysis Set By Study
Study
Patients
Treated,
n Exposure to G-CSF, mg G-CSF Doses, n
Baseline Disease
Stage, %
Phase 3 SCLC [5]
Filgrastim only (n=100) 100 Median, 23.5
Range, 1.1–60.4
Median, 65
Range, 3.0–126
Limited: 27
Extensive: 73
Placebo then filgrastima
(n=73) 73 Median, 18.6
Range, 3.0–26.1
Median, 50
Range, 11–71
Limited: 29
Extensive: 71
Placebo only (n=34) 34 NA NA Limited: 23
Extensive: 77
Phase 3 breast [6]
Pegfilgrastim only (n=467) 467 Median, 24.0
Range, 6.0–36.0
Median, 4.0
Range, 1.0–4.0
Nonmetastatic: 19
Metastaticb
: 81
Placebo then pegfilgrastima
(n=89) 89 Median, 18.0
Range, 6.0–18.0
Median, 3.0
Range, 1.0–3.0
Nonmetastatic: 9
Metastatic: 91
Placebo only (n=465) 372 NA NA Nonmetastatic: 18
Metastaticb
: 82
Phase 2 CRC [7]
Pegfilgrastim (n=126) 124 Mean, 21.5
SD, 5.4
Median, 24.0
Range, 6.0–24.0
Stage 2: 0.8
Stage 3: 0.8
Stage 4: 95
Not assessed: 3
28. Placebo only (n=126) 117 NA NA Stage 2: 0
Stage 3: 1.6
Stage 4: 97
Not assessed: 1.6
Noninferiority 1: phase 3 breast [8]
Pegfilgrastim (n=80) 79 Mean, 23.5
SD, 2.5
Mean, 3.9
SD, 0.4
Stage 2: 25
Stage 3: 27
Stage 4: 48
Filgrastim (n=77) 76 Mean, 15.0
SD, 4.1
Mean, 41.5
SD, 8.2
Stage 2: 31
Stage 3: 27
Stage 4: 43
Noninferiority 2: phase 3 breast [9]
Pegfilgrastim (n=154) 150 Mean, 29.1
SD, 9.5
Mean, 3.8
SD, 0.7
Stage 2: 49
Stage 3: 26
Stage 4: 25
Filgrastim (n=156) 151 Mean, 15.5
SD, 4.4
Mean, 41.0
SD, 8.7
Stage 2: 56
Stage 3: 25
Stage 4: 19
CRC=colorectal cancer; G-CSF=granulocyte colony-stimulating factor; NA=not applicable; SCLC=small cell lung
cancer; SD=standard deviation.
a
Patients randomized to placebo who crossed over to receive open-label filgrastim/pegfilgrastim as a result of febrile neutropenia
during cycle 1.
b
Stages 3 and 4 combined.
29. Table 4. Kaplan-Meier Estimates of Overall Survival and 6- and 12-Month Survival Rates in the Safety Analysis Seta,b
Study
Events,
n/N (%)
Censored,c
n/N (%)
Median OS,
mo (95% CI)
6-Month
Survival,
% (95% CI)
12-Month
Survival,
% (95% CI)
Unadjusted HR
(95% CI)
Phase 3 SCLC [5]
Filgrastim only 52/100 (52.0) 48/100 (48.0) 14.1 (10.6–NE) 87.0 (80.4–93.6) 55.0 (45.2–64.8)
0.81 (0.48–1.35)
P=0.412
Placebo then
filgrastimd 39/73 (53.4) 34/73 (46.6) 16.9 (13.0–NE) 91.8 (85.5–98.1) 67.1 (56.3–77.9)
0.75 (0.43–1.28)
P=0.286
Placebo only 20/34 (58.8) 14/34 (41.2) 11.1 (9.0–NE) 76.5 (62.2–90.7) 44.1 (27.4–60.8) Reference
Phase 3 breast [6]
Pegfilgrastim only 5/467 (1.1) 462/467 (98.9) NE NE NE
0.40 (0.14–1.17)
P=0.094
Placebo then
pegfilgrastimd 4/89 (4.5) 85/89 (95.5) NE NE NE
1.62 (0.51–5.17)
P=0.414
Placebo only 10/372 (2.7) 362/372 (97.3) NE NE NE Reference
Phase 2 CRC [7]
Pegfilgrastime
47/124 (37.9) 77/124 (62.1) NE (19.0–NE) 88.6 (82.8–94.5) 80.0 (72.5–87.5)
0.81 (0.54–1.20)
P=0.292
Placebo 50/117 (42.7) 67/117 (57.3) 24.8 (19.0–NE) 85.7 (79.0–92.4) 72.0 (63.1–80.8) Reference
Noninferiority 1: phase
3 breast [8]
Pegfilgrastim 2/79 (2.5) 77/79 (97.5) NE 97.4 (93.8–100) NE
NE
P=0.608
Filgrastim 3/76 (3.9) 73/76 (96.1) NE 94.6 (88.2–100) NE Reference
30. Noninferiority 2: phase
3 breast [9]
Pegfilgrastim 18/150 (12.0) 132/150 (88.0) NE 98.6 (96.8–100) 94.4 (90.7–98.2)
NE
P=0.092
Filgrastim 30/151 (19.9) 121/151 (80.1) 32.8 (NE–NE) 97.3 (94.7–99.9) 94.6 (90.9–98.2) Reference
CI=confidence interval; CRC=colorectal cancer; HR=hazard ratio; NE=not estimable; OS=overall survival; SCLC=small cell lung
cancer.
a
Median survival = NE because number of events insufficient to reach the median.
b
Estimates of 6- and 12- month survival = NE because of insufficient time on study.
c
Patients who had not died at the time of the analysis were censored at the date they were last known to be alive.
d
Patients randomized to placebo who crossed over to receive open-label filgrastim/pegfilgrastim after cycle 1 as a result of febrile
neutropenia.
e
Includes three patients randomized to placebo who crossed over to receive open-label filgrastim/pegfilgrastim after cycle 1 as a
result of febrile neutropenia.