Qualification and impact of a video-assisted control system in a chemotherapy compounding unit.

OBJECTIVES: Anticancer drug preparation control is essential to ensure quality and patient safety. Drugcam (Eurekam Company) is a digital video-assisted control system based on artificial intelligence methods to identify vials used and volumes withdrawn. As for any control system, qualification is required before use in a chemotherapy compounding unit (CCU). METHODS: We conducted an operational qualification (sensitivity, specificity and accuracy assessment of vials and volumes recognition and quantitative analysis of measured volumes) and a performance qualification (comparison with visual control) of Drugcam in our CCU, as well as an impact study on compounding time and compound supply time. RESULTS: Sensitivity, specificity and accuracy of vials (94%, 98% and 96%, respectively) and volumes (86%, 96% and 91%, respectively) recognition are satisfactory. It depends on both the object presented and the camera tested. False positives, which could lead to release of non-compliant preparation, were detected. Volume reading errors may exceed the tolerance threshold of ±5% for small volumes. Drugcam did not significantly lengthen compounding time and compound supply time. CONCLUSIONS: No recommendations for a qualification method of this new type of control equipment exist. However, a qualification process is essential to understand tool limitations and integrate them into the CCU risk management system. Drugcam enables anticancer drug preparation to be secure and is also useful for initial and continuous staff training.

Efficacy and tolerance of LV5FU2-carboplatin chemotherapy in patients with advanced pancreatic ductal adenocarcinoma after failure of standard regimens.

Background: Chemotherapy options in patients with advanced pancreatic ductal adenocarcinoma (PDAC) after failure of standard chemotherapies are limited. Objectives: We aimed to report the efficacy and safety of the leucovorin and 5-fluorouracil (LV5FU2) and carboplatin combination in this setting. Design: We performed a retrospective study including consecutive patients with advanced PDAC who received LV5FU2-carboplatin between 2009 and 2021 in an expert center. Methods: We measured overall survival (OS) and progression-free survival (PFS), and explored associated factors using Cox proportional hazard models. Results: In all, 91 patients were included (55% male, median age 62), with a performance status of 0/1 in 74% of cases. LV5FU2-carboplatin was mainly used in third (59.3%) or fourth line (23.1%), with three (interquartile range: 2.0-6.0) cycles administered on average. The clinical benefit rate was 25.2%. Median PFS was 2.7 months (95% CI: 2.4-3.0). At multivariable analysis, no extrahepatic metastases (p = 0.083), no ascites or opioid-requiring pain (p = 0.023), <2 prior treatment lines (p < 0.001), full dose of carboplatin (p = 0.004), and treatment initiation >18 months after initial diagnosis (p < 0.001) were associated with longer PFS. Median OS was 4.2 months (95% CI: 3.48-4.92) and was influenced by the presence of extrahepatic metastases (p = 0.058), opioid-requiring pain or ascites (p = 0.039), and number of prior treatment lines (0.065). Prior tumor response under oxaliplatin did not impact either PFS or OS. Worsening of preexisting residual neurotoxicity was infrequent (13.2%). The most common grade 3-4 adverse events were neutropenia (24.7%) and thrombocytopenia (11.8%). Conclusion: Although the efficacy of LV5FU2-carboplatin appears limited in patients with pretreated advanced PDAC, it may be beneficial in selected patients.

Microangiopathy associated with gemcitabine: a drug interaction with nab-paclitaxel? A case series and literature review.

PURPOSE: Gemcitabine and nab-paclitaxel association can be used in first- or second-line treatment for metastatic pancreatic adenocarcinoma. Here, we report five cases of supposed gemcitabine-induced thrombotic microangiopathy (G-TMA), four of them with nab-paclitaxel. We assumed that nab-paclitaxel could be responsible for a potential drug interaction with gemcitabine, increasing the risk of thrombotic microangiopathy occurrence. METHODS: Clinicians reported cases of supposed G-TMA that were declared to the Pharmacovigilance center. We collected the patients' data (clinical and biological characteristics), calculated an incidence rate of G-TMA in our center, and a Naranjo score for each patient. We also reviewed literature on a potential drug interaction between nab-paclitaxel and gemcitabine. RESULTS: Four patients were treated with nab-paclitaxel/gemcitabine and one with gemcitabine alone. The time onset of supposed G-TMA was 2 to 11 months. Patients developed anemia, thrombocytopenia, and renal failure. The incidence rate of supposed G-TMA was 2.7% in our center compared to 0.31% (Meyler's Side Effect of Drugs) and 0.01% in the gemcitabine's summary of product characteristics. Literature review outlined an increase of gemcitabine's plasmatic concentrations induced by nab-paclitaxel (Drugs® website) and a potentiation of gemcitabine's effect by nab-paclitaxel in murine models. This study showed that nab-paclitaxel inhibits cytidine deaminase's activity (responsible for gemcitabine's metabolism) and increases gemcitabine's active metabolite concentrations (gemcitabine triphosphate) in tumor tissues. CONCLUSION: High incidence rate of G-TMA was observed in our cohort due to a potential drug interaction between nab-paclitaxel and gemcitabine with an increased risk of developing G-TMA. Additional pharmacological and pharmaco-epidemiological investigations are mandatory to explore this hypothesis.

PARP inhibition in treatment of pancreatic cancer.

INTRODUCTION: Tumor control and survival of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) has improved with more effective polychemotherapies. The identification of novel therapeutic targets is strongly needed in order to propose maintenance therapies that improve quality of life while maintaining tumor control. AREAS COVERED: PDAC with mutations in homologous recombination repair genes such as BRCA are particularly sensitive to platinum agents. Recently, the potential role of poly(ADP-ribose) polymerase (PARP) inhibitors was suggested. The POLO study has shown that olaparib was efficient and well-tolerated as maintenance therapy in patients with germline BRCA1/2 mutation and a metastatic PDAC controlled after a platinum-based induction chemotherapy. EXPERT OPINION: The demonstration of olaparib efficacy in patients with metastatic PDAC and BRCA germline mutation has paved the way for maintenance with a targeted therapy. Further studies are needed to assess; the potential role for PARPI in earlier forms of PDAC, those with somatic or more rare BRACness signatures, to overcome primary or secondary resistances to PARPi, and to combine them with other antitumoral agents.