SummaryBackgroundData suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival.MethodsFOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1:1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m2 oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m2 oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary endpoint was overall survival, analysed in the intention-to-treat population, using a two-stage meta-analysis of pooled individual patient data. All three trials have completed 2 years of follow-up. FOXFIRE is registered with the ISRCTN registry, number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with ClinicalTrials.gov, numbers NCT00724503 (SIRFLOX) and NCT01721954 (FOXFIRE-Global).FindingsBetween Oct 11, 2006, and Dec 23, 2014, 549 patients were randomly assigned to FOLFOX alone and 554 patients were assigned FOLFOX plus SIRT. Median follow-up was 43·3 months (IQR 31·6–58·4). There were 411 (75%) deaths in 549 patients in the FOLFOX alone group and 433 (78%) deaths in 554 patients in the FOLFOX plus SIRT group. There was no difference in overall survival (hazard ratio [HR] 1·04, 95% CI 0·90–1·19; p=0·61). The median survival time in the FOLFOX plus SIRT group was 22·6 months (95% CI 21·0–24·5) compared with 23·3 months (21·8–24·7) in the FOLFOX alone group. In the safety population containing patients who received at least ...

Background The interim analysis of the multicentre New EPOC trial in patients with resectable colorectal liver metastasis showed a significant reduction in progression-free survival in patients allocated to cetuximab plus chemotherapy compared with those given chemotherapy alone. The focus of the present analysis was to assess the effect on overall survival.Methods New EPOC was a multicentre, open-label, randomised, controlled, phase 3 trial. Adult patients (aged ≥18 years) with KRAS wild-type (codons 12, 13, and 61) resectable or suboptimally resectable colorectal liver metastases and a WHO performance status of 0-2 were randomly assigned (1:1) to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done centrally with minimisation factors of surgical centre, poor prognosis cancer, and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m² administered intravenously over 2 h, l-folinic acid (175 mg flat dose administered intravenously over 2 h) or d,l-folinic acid (350 mg flat dose administered intravenously over 2 h), and fluorouracil bolus 400 mg/m² administered intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m² repeated every 2 weeks (regimen one), or oxaliplatin 130 mg/m² administered intravenously over 2 h and oral capecitabine 1000 mg/m² twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m² intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given intravenously, 500 mg/m² every 2 weeks with regimen one and three or a loading dose of 400 mg/m² followed by a weekly infusion of 250 mg/m² with regimen two. The primary endpoint of progression-free survival was published previously. Secondary endpoints were overall survival, preoperative response, pathological resection status, and safety. Trial recruitment was halted prematurely on the advice of the Trial Steering Committee on Nov 1, 2012. All analyses (except safety) were done on the intention-totreat population. Safety analyses included all randomly assigned patients. This trial is registered with ISRCTN, number 22944367.

No abstract

No abstract

gence (Martens and Westermann, 1991). These studies have not investigated a complete range of Zn seed treat-Zinc seed treatments for rice (Oryza sativa L.) were previously ment rates and sources to compare with standard soil evaluated as an alternative to soil-applied Zn. Recommendations concerning the effectiveness of Zn seed treatments were never clearly or foliar Zn fertilization methods. stated. Our objectives were to evaluate the utility of Zn seed treat- Martens et al. (1973) concluded that band application ments for supplying Zn to rice grown on soils prone to Zn deficiency.of Zn fertilizer in contact with the corn (Zea mays L.)In 1998, a study with three cultivars compared Zn-treated seeds [2.8 g seeds at rates ranging from 0.34 to 1.34 kg Zn ha Ϫ1 Zn (kg seed) Ϫ1 ] with a control and 11 kg Zn ha Ϫ1 as ZnSO 4 applied produced grain yields equal to those achieved when 26.9 to the soil. Because tissue Zn concentration did not differ among kg Zn ha Ϫ1 as ZnSO 4 was broadcast on the soil surface cultivars, a single cultivar, Drew, was used in studies at two locations and incorporated before planting. Earlier research with in 1999. The control and the soil-applied Zn were compared with rice (Haghighat and Thompson, 1982; Giordano and seeds that were treated with three rates of ZnSO 4 and ZnEDTA Mortvedt, 1973; Mengel et al., 1976; Rush, 1972) also (ethylenediaminetetraacetic acid). Analysis showed net seed concensuggested that the application of low rates of Zn to rice trations of 1.0, 2.2, and 4.7 g Zn (kg seed) Ϫ1 as ZnSO 4 and 1.4, 2.8, and 5.7 g Zn (kg seed) Ϫ1 as ZnEDTA. In 1998, neither visual Zn seeds or dipping the roots of transplanted rice in a Zn deficiency symptoms nor significant yield differences were observed solution may be effective alternatives to broadcast appliamong treatments. Soil-applied Zn and Zn seed treatments increased cations of Zn fertilizer. tissue Zn concentration by 11.9 and 4.7 mg Zn kg Ϫ1 , respectively, In Arkansas, Zn fertilizer recommendations for rice above that of the control (19.7 mg Zn kg Ϫ1 ). In 1999, Zn deficiency are currently based on the soil pH and texture. Zinc is occurred at both locations. Measurements of dry matter, tissue Zn recommended for rice, regardless of soil test Zn levels, concentration, and grain yield showed that Zn-treated seed performed grown on silt and sandy loam soils having a pH Ͼ6.5. equal to or better than soil-applied Zn. These data suggest that seed Zn Sedberry et al. (1980) and Wells (1980) both found the concentrations between 2.2 to 5.7 g Zn (kg seed) Ϫ1 are an economical soil pH to best predict rice response to Zn fertilization alternative to soil-applied Zn.during the early 1970s. However, much of this research was conducted before the widespread use of Zn fertilizers. Since the development of Zn fertilizer recommendations,