Pathogen distribution and, consequently, drug susceptibility seem to vary across different geographic regions. Furthermore, protection from invasive zygomycosis for patients on posaconazole prophylaxis is not absolute. Our findings indicate that the use of liposomal amphotericin B as first-line treatment for patients diagnosed with zygomycoses merits further investigation, preferably in the form of a clinical trial.

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4502 Background: Perioperative FLOT is a standard of care for resectable, esophagogastric adenocarcinoma (EGA). This trial evaluates the addition of trastuzumab (tras) and pertuzumab (per) to FLOT for HER2-positive resectable patients (pts). Methods: PETRARCA is a prospective, multicenter, randomized, investigator initiated trial planned as a phase II/III investigation. We report the phase II part of this trial. Pts with HER2+ resectable EGA (≥ cT2 or cN+) were enrolled. Pts were randomized 1:1 to 4 pre- and post-operative cycles of FLOT (Docetaxel 50 mg/m²; Oxaliplatin 85 mg/m²; Leucovorin 200 mg/m²; 5-FU 2600 mg/m², q2w) (Arm A) or the same regimen with tras 8/6 mg/kg and per 840 mg q3w, followed by 9 cycles tras/per (arm B). Primary endpoint for the phase II part was the rate of pathological complete remission (pCR). Main secondary endpoints were DFS, OS and safety. Results: The trial closed prematurely and did not proceed to phase III. In total, 81 pts were randomized (A, 41; B, 40). Baseline characteristics were balanced (overall, male 79%; median age 60; cT3/T4 86%; cN+ 85%; GEJ 75%). 93% in arm A and 90% in arm B completed pre-OP treatment as planned. More pts had at least one dose modification in arm B (A, 44%; B, 70%). The pCR rate was significantly improved with tras/per (A, 12%; B, 35%; p = 0.02). Likewise, the rate of pathological lymph node negativity was higher with tras/per (A, 39%; B, 68%). R0-resection rate (A, 90%; B, 93%) and surgical morbidity (A: 43%; B, 44%) were comparable. Moreover, in-house mortality was equal in both arms (overall 2.5%). Median DFS was 26 months in arm A and not yet reached in arm B (HR 0.58, p = 0.14). After a median follow-up of 22 months median OS was not yet reached. DFS and OS rates [with 95% CI] at 24 months were 54% [38-71%] and 77% [63-90%] in arm A and 70% [55-85%] and 84% [72-96%] in arm B, respectively. In terms of toxicity more ≥ grade 3 adverse events were reported with tras/per (75% vs. 85%), especially diarrhea (5% vs. 41%) and leukopenia (13% vs 23%). Conclusions: The addition of tras/per to perioperative FLOT significantly improved pCR and nodal negativity rates in pts with Her2+ resectable esophagogastric adenocarcinoma at the price of higher rates of diarrhea and leukopenia. Clinical trial information: NCT02581462 .

Background: Palliative chemotherapy of advanced oesophageal squamous cell cancer (ESCC) consists of cisplatin/5fluorouracil (CF) to target epidermal growth factor receptor (EGFR) with panitumumab (P); chemotherapy enhanced overall survival (OS) in advanced colorectal or squamous cell head and neck cancers. With prospective serum and tumour biomarkers, we tested if P added to CF (CFP) improved OS in advanced ESCC. Patients and methods: Eligible patients with confirmed ESCC that was not curatively resectable or did not qualify for definitive radiochemotherapy, were randomised 1 : 1 to receive CF [cisplatin (C) 100 mg/m 2 i.v., day 1; 5-fluorouracil (F) 1000 mg/m 2 i.v., days 1e4] or CF plus P (9 mg/kg, i.v., day 1, each q3-week cycle) until progressive disease or unacceptable toxicity. Safety was reviewed by the Data Safety Monitoring Board after 40, 70 and 100 patients who completed at least one cycle. After 53 enrolled patients, cisplatin was reduced from 100 mg/m 2 to 80 mg/m 2. Results: The trial was stopped early based on interim efficacy results triggered by the third safety analysis: median OS (mOS) favoured CF over CFP, regardless of cisplatin dose [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.06e2.98; P ¼ 0.028]. In the final analysis, mOS was 10.2 versus 9.4 months for CF versus CFP, respectively (HR 1.17, 95% CI 0.79 e1.75; P ¼ 0.43). One hundred (70.4%) of 142 patients in the safety population died, 51 (51.0%) with CFP. Most deaths were related to disease progression [44/49 (90%) deaths in CF versus 34/51 (67%) deaths in CFP]; objective responses [27/73 (37.0%)] were identical. The most common serious adverse events were kidney injury [3 (4.3%) versus 7 (9.7%)], general health deterioration [5 (7.1%) versus 5 (6.9%)] and dysphagia [4 (5.7%) versus 4 (5.6%)] in CF versus CFP, respectively. There were three (4.3%) and 17 (23.6%) common terminology criteria for adverse events (CTCAE) grade 5 events in CF versus CFP, respectively. Low soluble (s)EGFR levels were associated with better progression-free survival; sEGFR was induced under CFP. Conclusion: EGFR inhibition added to CF did not improve survival in unselected advanced ESCC patients. The results support further liquid biopsy studies. Trial registration: ClinicalTrials.gov (NCT01627379) and EudraCT (2010-020606-15).

Background: Studies in animal models of inflammatory bowel disease (IBD) suggest that supplementation of total parenteral nutrition with glutamine (gln), a conditionally essential amino acid in catabolic conditions, increases gln plasma concentrations, reduces intestinal damage, improves nitrogen balance and may improve the course of the disease. However, human data supporting this assumption are missing. Methods: A total of 24 consecutive patients with an acute exacerbation of IBD (19 Crohn's disease; five ulcerative colitis) and scheduled for total parenteral nutrition (TPN) (47 days) were randomised. Parallel to a standardised anti-inflammatory therapy, the patients received either a TPN with 1.5 g/kg body weight of a standard amino acid or an isonitrogenic, isocaloric TPN with 1.2 g/kg body weight of a standard amino acid and 0.3 g/kg L-alanine-L-glutamine. Primary end points were gln plasma concentrations and intestinal permeability assessed by urinary lactulose and D-xylose ratio. Results: Gln plasma levels did not differ significantly in either group throughout the study. Intestinal permeability did not change within 7 days either with or without gln supplementation (D-lactulose/xylose ratio: 0.0170.05 (gln þ ) vs 0.0270.1 (glnÀ)). The observed changes in inflammatory and nutritional parameters, and also disease activity, length of TPN and hospital stay, were independent of glutamine substitution. Five (41%) patients in the gln þ group and three (25%) patients in the glnÀ group needed surgical intervention. Conclusion: Although limited by the sample size, these results do not support the hypothesis that glutamine substitution has an obvious biochemical or clinical benefit in patients with active IBD scheduled for total parenteral nutrition.