Oxaliplatin plus irinotecan vs irinotecan as second-line treatment in pancreatic cancer patients:a randomized–controlled open-label Phase II study

Background:Limited second-line therapeutic options are available for metastasis pancreatic cancer(mPC).We aimed to explore the efficacy and safety of oxaliplatin plus irinotecan(IROX)in mPC patients.Methods:This is an open-label,Phase 2,randomized study of mPC patients(aged 18–75 years)who failed when using gemcitabine plus S-1 as first-line therapy.Block randomization with a block size of four was used to randomly assign patients(1:1)between October 2015 and December 2017 to receive either IROX(oxaliplatin 85mg/m2 and irinotecan 160mg/m2)or irinotecan monotherapy(irinotecan 180mg/m^(2))until disease progression,unacceptable adverse events,or consent withdrawal.The primary end point was overall survival,and the secondary end points were progression-free survival,overall response rate,and adverse event rate.Results:A total of 74 patients were enrolled in this study,including 44 males and 30 females,with an average age of 61 years.The median overall survival was 10.2 and 6.7 months(adjusted hazard ratio[HR],0.7;95%confidence interval[CI],0.4–1.2;P=0.20)and the median progression-free survival was 5.1 and 2.3 months(adjusted HR,0.4;95%CI,0.2–0.6;P<0.01)in the IROX group and irinotecan group,respectively.The overall response rates were 18.4%(7/38)in the IROX group and 5.5%(2/36)in the irinotecan group(P=0.06).Grade 3–4 adverse events occurred in 34%(13/38)of patients in the IROX group and 19%(7/36)of patients in the irinotecan group(P=0.15).Conclusions:IROX had no significant survival benefit over irinotecan monotherapy in our study.However,IROX reduced the risk of disease progression by 60%,with acceptable toxicity.

Simultaneous detection and characterization of toxigenic Clostridium difficile directly from clinical stool specimens

We employed a multiplex polymerase chain reaction （PCR） coupled with capillary electrophoresis （mPCR-CE） targeting six Clostridium difficile genes, including tPi, tcdA, tcdB, cdtA, cdtB, and a deletion in tcdC for simultaneous detection and characterization of toxigenic C. difficile directly from fecal specimens. The mPCR-CE had a limit of detection of 10 colony-forming units per reaction with no cross-reactions with other related bacterial genes. Clinical validation was performed on 354 consecutively collected stool specimens from patients with suspected C. difficile infection and 45 isolates. The results were compared with a reference standard combined with BD MAX Cdiff, real-time cell analysis assay （RTCA）, and mPCR-CE. The toxigenic C. difficile species were detected in 36 isolates and 45 stool specimens by the mPCR-CE, which provided a positive rate of 20.3% （81/399）. The mPCR-CE had a specificity of 97,2% and a sensitivity of 96.0%, which was higher than RTCA （χ^2 = 5.67, P = 0.017） but lower than BD MAX Cdiff （P = 0.245）. Among the 45 strains, 44 （97.8%） were determined as non- ribotype 027 by the mPCR-CE, which was fully agreed with PCR ribotyping. Even though ribotypes 017 （n = 8, 17.8%）, 001 （n = 6, 13.3%）, and 012 （n = 7, 15.6%） were predominant in this region, ribotype 027 was an important genotype monitored routinely. The mPCR-CE provided an alternative diagnosis tool for the simultaneous detection of toxigenic C. difficile in stool and potentially differentiated between RT027 and non-RT027.