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The RADPAC trial evaluated paclitaxel with everolimus in patients with advanced gastroesophageal cancer (GEC) who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen. Patients were randomly assigned to receive paclitaxel (80 mg/m 2 ) on day 1, 8 and 15 plus everolimus (10 mg daily, arm B) d1-d28 or placebo (arm A), repeated every 28 days. Primary end point was overall survival (OS). Efficacy was assessed in the intention-to-treat population and safety in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, number NCT01248403. Between October 2011 and September 2015, 300 patients (median age: 62 years; median lines prior therapy: 2; 47.7% of patients had prior taxane therapy) were randomly assigned (arm A, 150, arm B, 150). In the intention to treat population, there was no significant difference in progression-free survival (PFS; everolimus, 2.2 vs placebo, 2.07 months, HR 0.88, P = .3) or OS (everolimus, 6.1 vs placebo, 5.0 months, HR 0.93, P = .54). For patients with prior taxane use, everolimus improved PFS (everolimus, 2.7 vs placebo 1.8 months, HR 0.69, P = .03) and OS (everolimus, 5.8 vs placebo 3.9 months, HR 0.73, P = .07). Combination of paclitaxel and everolimus was associated with significantly more grade 3-5 mucositis (13.3% vs 0.7%; P < .001). The addition of everolimus to paclitaxel did not improve outcomes in pretreated metastatic gastric/gastroesophageal junction (GEJ) cancer. Activity was seen in the taxane pretreated group. Additional biomarker studies are planned to look for subgroups that may have a benefit., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: In metastatic colorectal cancer, no upfront or on-treatment markers are available to determine the prognosis or efficacy for chemotherapy in combination with bevacizumab., Patients and Methods: The current analysis was performed to evaluate the prognostic value of disease and patient characteristics (age, number of metastatic sites, stage of primary tumor, performance status, carcinoembryonic antigen (CEA)) and on-treatment changes of CEA (response after 8-12 weeks of treatment and specific patterns of CEA kinetics) in patients from an observational cohort study of chemotherapy with bevacizumab., Results: Baseline factors were available from 1,438 patients. Patients with baseline CEA levels > 20 ng/ml, more than 1 metastatic site, and age > 75 years showed significantly lower progression-free (PFS) and overall survival in multivariate analysis. A CEA response of > 30% during treatment was associated with increased PFS. In addition, the pattern of CEA kinetics predicts survival and response to treatment., Conclusion: In summary, baseline CEA, number of metastatic sites, and age are strong independent prognostic factors for survival. By monitoring CEA, clear patterns with distinct prognostic value can be determined. CEA kinetics and/or response after 8-12 weeks might be a useful and simple tool to stratify the post-induction treatment approach based on individual prognosis in the future., (© 2017 S. Karger GmbH, Freiburg.)

Background: After approval of bevacizumab in Germany in 2005 for the treatment of unresectable advanced or refractory colorectal cancer (CRC), this observational cohort study was initiated to assess the efficacy and safety of bevacizumab with various chemotherapy regimen in patients with metastatic CRC (mCRC)., Material and Methods: To facilitate enrolment of a typical mCRC population, eligibility criteria were minimised. Choice of chemotherapy regimen was at the physicians' discretion, but influenced by current registration status. Predefined endpoints were treatment characteristics, response rate, progression-free survival (PFS), overall survival (OS) and adverse events assessed as potentially related to bevacizumab treatment. Patients were followed for up to four years., Results: In total 1777 eligible patients were enrolled at 261 sites from January 2005 to June 2008. Median age: 64 years (range 19-100); male 62%; ECOG performance status 0-1/≥ 2 89%/11%. Chemotherapy choice was fluoropyrimidine (FU) 12%, FU/oxaliplatin 18%, FU/irinotecan 64%, no chemotherapy concurrent to bevacizumab 2% and other 4%. Best investigator-assessed response rate was 60% (complete response 10%, partial response 51%). Median PFS was 10.2 months and median OS was 24.8 months., Conclusions: The efficacy and safety profile of bevacizumab in this population of mCRC patients with different chemotherapy regimens is consistent with that observed in other patient registries/non-randomised trials and also corresponds well with data from similar treatment arms of phase III trials.

Background: To evaluate the efficacy of first-line bevacizumab-based chemotherapy for untreated metastatic colorectal cancer (mCRC) based on age., Methods: Eligibility criteria focused on M1 disease without prior palliative chemotherapy. Choice of chemotherapy regimen was at the physician's discretion. Predefined efficacy endpoints were response rate, progression-free and overall survival (PFS, OS). Patients were analysed by age (<70 vs. ≥70 years, <75 vs. ≥75 years)., Results: Of 1777 patients, 27% and 12% were ≥70 and ≥75 years, respectively. PFS was shorter in elderly patients (<70 vs. ≥70 years: 10.5 vs. 9.5 months, p = 0.074; <75 vs. ≥75 years: 10.5 vs. 8.9 months, p = 0.00019), as was OS (<70 vs. ≥70 years: 25.8 vs. 22.7 months, p < 0.0008; <75 vs. ≥75 years: 25.8 vs. 20.8 months; p < 0.0001). In the groups <70 and <75 years, PFS was longer in those receiving oxaliplatin-/irinotecan-containing regimens vs. those receiving 5-FU/capecitabine (<70 years: 10.6 vs. 9.0 months; p = 0.0065; <75 years: 10.6 vs. 9.2 months; p = 0.028); no difference in PFS was observed between oxaliplatin-/irinotecan-containing regimens vs. 5-FU/capecitabine regimens in both elderly age-group comparisons (≥70 years: 9.7 vs. 9.2 months; ≥75 years: 8.3 and 9.0 months)., Conclusion: First-line bevacizumab-based chemotherapies were effective in German mCRC patients ≥75 years of age, but PFS and OS were significantly shorter in this age group vs. younger patients.

Purpose: To assess the efficacy of a second-line regimen of oxaliplatin and folinic acid-modulated fluorouracil in patients with advanced pancreatic cancer who have experienced progression while receiving gemcitabine monotherapy., Patients and Methods: A randomized, open-label, phase III study was conducted in 16 institutions throughout Germany. Recruitment ran from January 2004 until May 2007, and the last follow-up concluded in December 2012. Overall, 168 patients age 18 years or older who experienced disease progression during first-line gemcitabine therapy were randomly assigned to folinic acid and fluorouracil (FF) or oxaliplatin and FF (OFF). Patients were stratified according to the presence of metastases, duration of first-line therapy, and Karnofsky performance status., Results: Median follow-up was 54.1 months, and 160 patients were eligible for the primary analysis. The median overall survival in the OFF group (5.9 months; 95% CI, 4.1 to 7.4) versus the FF group (3.3 months; 95% CI, 2.7 to 4.0) was significantly improved (hazard ratio [HR], 0.66; 95% CI, 0.48 to 0.91; log-rank P = .010). Time to progression with OFF (2.9 months; 95% CI, 2.4 to 3.2) versus FF (2.0 months; 95% CI, 1.6 to 2.3) was significantly extended also (HR, 0.68; 95% CI, 0.50 to 0.94; log-rank P = .019). Rates of adverse events were similar between treatment arms, with the exception of grades 1 to 2 neurotoxicity, which were reported in 29 patients (38.2%) and six patients (7.1%) in the OFF and FF groups, respectively (P < .001)., Conclusion: Second-line OFF significantly extended the duration of overall survival when compared with FF alone in patients with advanced gemcitabine-refractory pancreatic cancer., (© 2014 by American Society of Clinical Oncology.)

The gold standard of cytogenetic analysis in myelodysplastic syndromes (MDS) is conventional chromosome banding (CCB) analysis of bone marrow (BM) metaphases. Most aberrations can also be detected by fluorescence-in situ-hybridization (FISH). For this prospective multicenter German diagnostic study (www.clinicaltrials.gov: #NCT01355913) 360 patients, as yet, were followed up to 3 years by sequential FISH analyses of immunomagnetically enriched CD34+ peripheral blood (PB) cells using comprehensive FISH probe panels, resulting in a total number of 19,516 FISH analyses. We demonstrate that CD34+ PB FISH correlates significantly with CCB analysis and represents a feasible method for a reliable non-invasive cytogenetic monitoring from PB., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Gemcitabine usually given until progressive disease (PD) is the main first-line treatment option for patients with inoperable advanced pancreatic cancer (APC). Currently there is no accepted active regimen for second-line chemotherapy. Previous phase II studies suggest clinical relevant activity of oxaliplatin, folinic acid and 5-FU (OFF). We initiated a phase III multicentre study comparing OFF versus best supportive care (BSC) in patients with APC progressing while on gemcitabine therapy., Methods: In this open randomized study, patients with CT and/or MRI confirmed progressive disease while on gemcitabine therapy were randomized 1:1 to OFF or BSC. Stratification included duration of first-line therapy (<3, 3 to 6 and >6 months), performance status (KPS 70-80%; 90-100%) and tumour stage (M1/M0). OFF consisted of folinic acid 200mg/m(2) followed by 5-fluorouracil 2g/m(2) (24h) on d1, d8, d15, d22 and oxaliplatin 85 mg/m(2) on days 8 and 22. After a rest of 3 weeks the next cycle was started on d43. A total of 165 patients were calculated to demonstrate a doubling of survival time after progression on first-line therapy., Results: After inclusion of forty six patients the trial was terminated according to predefined protocol regulations due to insufficient accrual (lack of acceptance of BSC by patients and physicians. Patient characteristics were well balanced between both study arms. The OFF regimen was well tolerated with more patients with grade I/II paraesthesia and grade II/III nausea/emesis and diarrhoea. Median second-line survival was 4.82 [95% Confidence Interval; 4.29-5.35] months for OFF treatment and 2.30 [95% CI; 1.76-2.83] months with BSC alone (0.45 [95% CI: 0.24-0.83], p = 0.008). Median overall survival for the sequence GEM-OFF was 9.09 [95% CI: 6.97-11.21] and 7.90 [95% CI: 4.95-10.84] months for GEM-BSC (0.50 [95% CI: 0.27-0.95], p = 0.031) respectively., Interpretation: Although stopped prematurely, this randomized trial provides at first time evidence for the benefit of second-line chemotherapy as compared to BSC alone for patients with APC. OFF significantly prolonged survival time compared to BSC alone after failure of first-line therapy with gemcitabine., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Knowledge of elbow collateral ligament length during passive motion is essential in understanding ligament physiology and pathology, such as tightness and instability., Methods: Five anatomical unembalmed specimens were passively placed in six flexion positions together with three forearm rotations, using equipment with gravity as motion force. These 18 positions were recorded using CT-scan. Three-dimensional data of ligament insertions were obtained through anatomical millimetre sections. Ligament length was measured in each position., Findings: In neutral rotation, the lateral collateral ligament was long between 0 degrees and 30 degrees as well as at 90 degrees, and short between about 60 degrees and 120 degrees of flexion. In pronation, it was long at about 0 degrees and between 60 degrees and 120 degrees, short at about 30 degrees of flexion. In supination, it was long at about 30 degrees and 90 degrees and short between 120 degrees and 150 degrees of flexion. In any forearm rotation, the highest length of the anterior bundle of the ulnar collateral ligament was measured at about 90 degrees, its smallest length between 120 degrees and 150 degrees of flexion, position at which the posterior bundle length was greatest., Interpretation: At 60 degrees of flexion, the collateral ligaments were slackened in any forearm rotations. Forearm rotation plays an indirect role in the posterolateral stability of elbow as it changes length of the lateral collateral ligament. This ligament can be tested passively at 90 degrees of flexion in supination, the anterior bundle of the ulnar collateral ligament between 0 degrees and 30 degrees in neutral rotation and the posterior bundle between 120 degrees and 150 degrees in neutral rotation.

S.A.M.U. 51 practises thrombolysis in patient's house associated with cardiologists of the University Hospital and of a Private Hospital, in indication and following for treatment. This way of working gives a large security for using this therapeutic to the whole population whatever the chosen hospital.

A case of Flumequine poisoning is described; a 13-year-old girl was admitted for a psychiatric syndrome. 3 hours after, seizures, coma, and metabolic disorders were observed. Infectious, encephalitic or diabetic diseases were suspected, but not confirmed. After 12 hours of a symptomatic treatment, the clinical status improved and the patient was discharged. At that time a tablet was found in her bedroom and a mas spectrographic analysis was positive for Flumequine. This case report is in agreement with previous observations and confirms the small therapeutic index of quinolone, and the absolute necessity to assess carefully a psychiatric diagnosis.