Platinum Plus Research Articles

2011 ADA Member Benefits Update

2011 ADA Member Benefits Update

A Meta-analysis of Platinum Plus Taxanes Regimen on Treating Advanced Non-small Cell Lung Cancer.

The platinum-based plus a third-generation agent doublet chemotherapy regimen has been recommended as the standard first-line chemotherapy for advanced NSCLC by ASCO and NCCN. This study was aimed to evaluate the clinical efficacy and side effects of the Platinum plus Taxanes or other novel agent. The databases PubMed, CENTRAL, EMBASE and Chinese Biomedical Literature database were retrieved by using the key words "non small cell lung cancer" or "Carcinoma, Non Small Cell Lung" so as to search the studies about the randomized controlled clinical trials, which compared Platinum plus Taxanes with Platinum plus other novel agents. A meta-analysis was conducted and the quality scores were evaluated according to the improved Jadad's score. Nine randomized controlled clinical trials with 4 703 patients were included. The overall response rate and 1 year survival rate of the two groups were not significantly different (RR=1.00, 95%CI: 0.91-1.11, P=0.95; RR=0.98, 95%CI: 0.84-1.15, P=0.83). The incidence rate of grade 3-4 leukopenia, neutropenia, anemia, nausea and vomiting in TP is much lower than that in platinum plus other novel agent. Sub-group analysis showed that the overall response rate and 1 year survival rate of TP aren't statistically different from NP or GP. The incidence rate of grade 3-4 leukopenia, neutropenia and anemia in TP is statistically lower than that in NP. The incidence rate of grade 3-4 anemia and thrombocytopenia in TP is statistically lower than that in GP. The clinical efficacy of TP and platinum plus other novel agent is quite similar, but quite different from each other in side effects, which provides important evidence on selecting individual chemotherapy regimen.

Safety and Efficacy of Darbepoetin Alfa in Previously Untreated Extensive-Stage Small-Cell Lung Cancer Treated With Platinum Plus Etoposide

A placebo-controlled, double-blind, randomized, phase III study was conducted in patients with extensive-stage small-cell lung cancer receiving first-line platinum-containing chemotherapy to determine if increasing or maintaining hemoglobin concentration with darbepoetin alpha could increase patient survival. Darbepoetin alpha (300 microg) or placebo was administered once per week for 4 weeks then every 3 weeks for up to six cycles of chemotherapy (carboplatin plus etoposide or cisplatin plus etoposide) plus 3 weeks after the last dose of chemotherapy. Patients with disease progression were observed until death or until all patients completed their end-of-study visit and 496 deaths had occurred. The two coprimary end points were change in hemoglobin concentration from baseline to the end of the chemotherapy period and overall survival; statistical testing of survival was done if change in hemoglobin was significant at P < .05. The study enrolled 600 patients. Patients' hemoglobin levels dropped due to the myelosuppressive chemotherapy; however, treatment with darbepoetin alpha maintained hemoglobin levels significantly higher than placebo (P < .001). There was no statistically significant difference in overall survival between the treatment groups (hazard ratio [HR], 0.93; 95% CI, 0.78 to 1.11; P = .431). As expected, darbepoetin alpha was associated with a higher incidence of thromboembolic events (darbepoetin alpha, 9%; placebo, 5%). The transfusion risk was lower in the darbepoetin versus placebo group (HR, 0.40; 95% CI, 0.29 to 0.55). The results of this study did not demonstrate improved survival after treatment with darbepoetin alpha; however, they reinforce the benefit of erythropoiesis-stimulating agents in reducing transfusions and their neutral impact on survival in patients with chemotherapy-induced anemia.

Pharmacogenetic Assessment of Toxicity and Outcome After Platinum Plus Taxane Chemotherapy in Ovarian Cancer: The Scottish Randomised Trial in Ovarian Cancer

Standard therapy for advanced ovarian cancer consists of a platinum agent in combination with a taxane, which has a 5-year survival rate of approximately 45%. The large individual variability for ovarian cancer patients in both outcome and toxicity risk from chemotherapy makes the identification of pharmacogenetic markers that can be used to screen patients before therapy selection an attractive prospect. We assessed 27 selected polymorphisms based on previously described associations or putative functional effects in 16 key genes from pathways that may influence cellular sensitivity to taxanes (ABCB1, ABCC1, ABCC2, ABCG2, CDKN1A, CYP1B1, CYP2C8, CYP3A4, CYP3A5, MAPT, and TP53) and platinum (ABCC2, ABCG2, ERCC1, ERCC2, GSTP1, MPO, and XRCC1) using polymerase chain reaction and Pyrosequencing in 914 ovarian cancer patients from the Scottish Randomised Trial in Ovarian Cancer phase III trial who were treated at presentation with carboplatin and taxane regimens after cytoreductive surgery. No reproducible significant associations between genotype and outcome or toxicity were found for any of the genes analyzed. Previously reported genotype associations could not be replicated in this large study of a well-defined patient population within one specific clinical trial. There are no clear candidates for taxane/platinum pharmacogenetic markers. This study highlights the need for validation of putative genetic markers in large, well-defined clinical sample sets.

Platinum Plus combined with specially catalyzed aftertreatment slash cost of diesel emission control

Platinum Plus combined with specially catalyzed aftertreatment slash cost of diesel emission control

Clean Diesel Technologies to supply Platinum Plus for reducing diesel particulate in mines

Clean Diesel Technologies to supply Platinum Plus for reducing diesel particulate in mines

Field trials confirm advantages from Platinum Plus diesel additive

The risk for pulmonary hypertension (PH) in thalassemia major (TM) patients remains controversial. We report echocardiography results from 60 TM patients: we evaluated the association between tricuspid regurgitation velocities (TRV), iron stores, and serologic markers of hemolysis and arginine dysregulation.Patients were enrolled from August 2004 until May 2009. All parameters were inversely weighted by the number of exams.TRV was comparable between sexes and it was uncorrelated with age. At the first exam, TR velocities at the upper limits of normal (2.5–2.7 m/s) were observed in 8 patients. An abnormal TRV (2.9 m/s) was found in 1 patient.Borderline increases in TRV were associated with a reduced global arginine bioavailability (R = − 0.399 P = 0.005), increased anemia (hemoglobin: R = − 0.219 P = 0.0461), cardiac index (R = 0.223 P = 0.0481), and diastolic dysfunction (E/A: R = 0.289 P = 0.0088; E/E′: R = 0.223 P = 0.0453), but not hemolysis, iron overload and systolic function evaluated by Magnetic Resonance Imaging, and splenectomy.Well-transfused TM patients have a lower risk for PH than thalassemia intermedia patients. However, they do have vascular stressors that raise their lifetime PH risk to levels higher than for the general population. Consequently, we support recommendations for annual echocardiographic screening and cardiac catheterization for persistent TRV above 3 m/s.