Efficacy of bevacizumab (Bev) plus chemotherapy (CT) compared to CT alone in previously untreated locally advanced or metastatic non-small cell lung cancer (NSCLC): systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy of chemotherapy (CT) plus Bevacizumab (Bev) versus CT alone in previously untreated locally advanced or metastatic non-small cell lung cancer (NSCLC). METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), progression-free survival (PFS) and side effects. We performed a meta-analysis (MA) of the published data, using a fixed effects model and an additional random effects model, when applicable. The results of the MA are expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (CI95%). We analyzed the use of Bev in the doses of 7.5 mg/kg and 15 mg/kg. RESULTS: The final analysis included 4 trials, comprising 2200 patients. The response rate was higher in patients who received the combination of CT plus Bev 7.5 mg/kg (RR=0.58; CI95%=0.46-0.74; p<0.00001) and Bev 15 mg/kg (RR=0.53; CI95%=0.45-0.63; p<0.00001) with moderate heterogeneity at dose of 15 mg/kg (Chi(2)=4.30, df=3 (P=0.23); I(2)=30%). The PFS length was longer in patients who received CT plus Bev 7.5 mg/kg (HR=0.78, CI95%=0.68-0.90; p=0.0005) and Bev 15 mg/kg (HR=0.72, CI95%=0.65-0.80; p<0.00001) with moderate heterogeneity (Bev 7.5 mg/kg: Chi(2)=1.43, df=1 (P=0.23); I(2)=30% and Bev 15 mg/kg: Chi(2)=7.43, df=3 (P=0.06); I(2)=60%). Differences in these end points remained in favor of CT plus Bev when made the analysis by random-effects model. Overall survival was longer in patients who received CT plus Bev 15 mg/kg (HR=0.89, CI95%=0.80-1.00; p=0.04), with moderate heterogeneity (Chi(2)=5.09, df=3 (P=0.17); I(2)=41%). The random-effects model analysis for this endpoint did not confirmed the difference seen in the fixed effects model analysis (HR=0.90, CI95%=0.76-1.07; p=0.23). Severe haematologic toxicities (grade>3), neutropenia and febrile neutropenia were more common among the patients that received Bev. CONCLUSION: The combination of CT plus Bev increased the response rate and progression-free survival of patients with NSCLC. With respect to overall survival the benefits of Bev remains uncertain.

Cost of the treatment of myelodisplastic syndrome in Brazil

INTRODUCTION: Myelodysplastic syndrome is an incurable and rare hematological disease that affects the production of blood cells. One aim of treatment is to maintain the blood-cell count to near-normal levels. This is mainly achieved with hematopoietic- growth factors and transfusions. Our objective was to determine the cost of supportive treatment/care for patients with low and intermediate I risk myelodysplastic syndrome in respect to private healthcare plans in Brazil. METHOD: We adapted the National Comprehensive Cancer Network treatment guidelines for intermediate risk myelodysplastic syndrome patients to the Brazilian reality, adopting a decision tree to explore treatment combinations. Then, we calculated the costs for each branch of the tree, according to national prices. We also estimated total costs for a cohort of 100 patients, distributed across treatment combinations according to the expected epidemiology. We assumed a horizon of one year of treatment. RESULTS: The mean cost of treatment for low and intermediate I risk myelodysplastic syndrome is US$ 42,758/patient/year. This cost can vary from US$ 24,282 to US$ 121,952, according to patient characteristics and the treatment used. Overall, patients that require immunotherapy with antithymocyte globulins are associated with the highest cost. Those that achieve disease stability solely with the use of erythropoietin were associated with the lowest cost. CONCLUSION: In Brazil, treatment of low and intermediate I risk myelodysplastic syndrome is associated with a mean cost of the order of US$ 42,700/patient/year. New types of therapy have the potential to change this scenario if they can diminish the requirements for supportive care.

Efficacy of palonosetron (PAL) compared to other serotonin inhibitors (5-HT3R) in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately or highly emetogenic (MoHE) treatment: systematic review and meta-analysis.

OBJECTIVE: The objective of this work is to perform a systematic review and meta-analysis of all randomized controlled trials comparing a single intravenous dose of palonosetron (PAL) 0.25 mg with other 5-HT(3)R in patients receiving moderately or highly emetogenic (MoHE) chemotherapy. METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were the incidence of acute and delayed nausea and vomiting. The side effects of each treatment were analyzed. A subgroup analysis was performed to evaluate the influence of the use of corticosteroids. The results are expressed as risk ratio (RR) and the correspondent 95% confidence interval (CI). RESULTS: Five studies were included, with 2057 patients. PAL was compared with ondansetron, granisetron, and dolasetron. Patients in PAL group had less nausea, both acute (RR = 0.86; CI 95% = 0.76 to 0.96; p = 0.007) and delayed (RR = 0.82; CI95% = 0.75 to 0.89; p < 0.00001). They also had less acute vomiting (RR = 0.76; CI 95% = 0.66 to 0.88; p = 0.0002) and delayed vomiting (RR = 0.76; CI95% = 0.68 to 0.85; p < 0.00001). There were no statistical differences in side effects like headache (RR = 0.84; CI 95% = 0.61 to 1.17; p = 0.30), dizziness (RR = 0.40; CI 95% = 0.13 to 1.27; p = 0.12), constipation (RR = 1.29; CI 95% = 0.77 to 2.17; p = 0.33) or diarrhea (RR = 0.67; CI 95% = 0.24 to 1.85; p = 0.44). Patients receiving PAL presented less nausea and vomiting regardless of the use of corticoids. We found no statistical heterogeneity in the global analysis. CONCLUSION: PAL was more effective than the other 5-HT(3)R in preventing acute and delayed CINV in patients receiving MoHE treatments, regardless of the use of concomitant corticosteroids.

Cost of the treatment of myelodisplastic syndrome in Brazil.

INTRODUCTION: Myelodysplastic syndrome is an incurable and rare hematological disease that affects the production of blood cells. One aim of treatment is to maintain the blood-cell count to near-normal levels. This is mainly achieved with hematopoietic- growth factors and transfusions. Our objective was to determine the cost of supportive treatment/care for patients with low and intermediate I risk myelodysplastic syndrome in respect to private healthcare plans in Brazil. METHOD: We adapted the National Comprehensive Cancer Network treatment guidelines for intermediate risk myelodysplastic syndrome patients to the Brazilian reality, adopting a decision tree to explore treatment combinations. Then, we calculated the costs for each branch of the tree, according to national prices. We also estimated total costs for a cohort of 100 patients, distributed across treatment combinations according to the expected epidemiology. We assumed a horizon of one year of treatment. RESULTS: The mean cost of treatment for low and intermediate I risk myelodysplastic syndrome is US$ 42,758/patient/year. This cost can vary from US$ 24,282 to US$ 121,952, according to patient characteristics and the treatment used. Overall, patients that require immunotherapy with antithymocyte globulins are associated with the highest cost. Those that achieve disease stability solely with the use of erythropoietin were associated with the lowest cost. CONCLUSION: In Brazil, treatment of low and intermediate I risk myelodysplastic syndrome is associated with a mean cost of the order of US$ 42,700/patient/year. New types of therapy have the potential to change this scenario if they can diminish the requirements for supportive care.