This study compares the performance of a reference method of HPLC to Raman spectroscopy (RS) for the analytical quality control (AQC) of complex therapeutic objects. We assessed a model consisting of a widely used anticancer drug, i.e., 5-fluorouracil, which was compounded in a complex medical device, i.e., an elastomeric portable infusion pump. In view of the main objective, the two methods provided excellent results for the analytical validation key criteria, i.e., trueness, precision and accuracy, ranging from 7.5 to 50mg/mL and in either isotonic sodium or 5% dextrose. The Spearman and Kendall correlation tests (p-value<1×10(-15)) and the statistical studies performed on the graphs confirm a strong correlation in the results between RS and the standard HPLC under the experimental conditions. The selection of a spectral interval between 700 and 1400cm(-1) for both the characterization and quantification by RS was the result of a gradual process optimization, combining matrix and packaging responses. In this new application, we demonstrate at least eight benefits of RS: (a) operator safety, (b) elimination of disposables, (c) elimination of analysis waste, which contributes to the protection of the environment, (d) a fast analytical response of less than 2min, (e) the ability to identify the solubilizing phase, (f) reduction of the risk of errors because no intrusion or dilution are needed, (g) negligible maintenance costs and (h) a reduction in the budget dedicated to technician training. Overall, we indicate the potential of non-intrusive AQC performed by RS, especially when the analysis is not possible using the usual techniques, and the technique's high potential as a contributor to the safety of medication.

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343 Background: There is no validated option beyond gemcitabine plus platinum standard first-line combination for advanced cholangiocarcinoma (CK). Second-line 5FU-based chemotherapy yields a median progression-free survival (PFS) and overall survival (OS) of 3 and 6-7 months, respectively. Intrahepatic CK subtypes overexpress VEGF, providing a rationale for testing sunitinib as second-line treatment in patients (pts) with advanced intrahepatic CK. Methods: A multicenter phase 2 study was designed for pts with locally advanced or metastatic intrahepatic CK after failure of first-line gemcitabine-based chemotherapy. Sunitinib was given at the dose of 37.5 mg/day continuously until disease progression or limiting toxicity. Pts were required to be ECOG PS 0-1 and with adequate liver function (alkaline phosphatase and transaminases < 5ULN, bilirubin <1.5ULN). Main objective was to exceed a median OS of 6.3 months. Secondary endpoints were PFS, response (RECIST 1.1 & Choi criteria), safety, pharmacokinetics (PK) and biomarker analysis (VEGFA, VEGFC, sKIT, HGF, SDF1, and osteopontin). Results: 53 pts were enrolled, with 34 pts evaluable for intermediate safety and efficacy analysis. Median age was 62 years (range 36–80), with 19 females/15 males. ECOG PS was 0/1 in 23/11 pts. Sixteen pts had prior surgical resection and 8 pts received adjuvant chemotherapy. Five pts (15%) had partial responses and 24 stable diseases (71%) by RECIST (disease control rate 85%). Ten pts had disease control > 6 months (range 6-14 months). With a median follow-up of 15.4 months, median OS was 9.6 months [95%CI: 5.8-13.1]. Median PFS was 5.2 months. Frequent adverse events were grade (Gr) 1-2 asthenia (80% of pts), mucositis (80%), diarrhea (60%), and hand-foot syndrome (43%). Gr 3/4 asymptomatic hematological toxicity occurred in 25% of pts (neutropenia n=8, thrombocytopenia n=7), Gr 3 hypertension was observed in 7 pts, and Gr 3 asthenia in 4 pts. Updated PK and biomarker analysis will be presented at the meeting. Conclusions: Second line sunitinib is well tolerated and shows promising activity with a 9.6-month OS in pts with advanced intrahepatic CK. Clinical trial information: NCT01718327.

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