Retrospective comparison of a weight-based dose every 2 weeks with a fixed dose every month: a real-life analysis of nivolumab in the treatment of advanced melanoma.

Nivolumab was first authorized at a weight-based dose (WBD) of 3 mg/kg every two weeks (Q2W). Since 2017, a fixed dose (FD) regimen [first 240 mg Q2W and then 480 mg per month (Q4W)] was allowed. The objective of the study was to compare a WBD regimen and an FD regimen with regard to effectiveness and safety. We conducted a single-center, retrospective, real-life study of consecutive adult patients who had received a WBD of nivolumab or an FD of 480 mg Q4W. The primary endpoint was the occurrence of grade ≥3 immune-related adverse events (irAEs). The secondary endpoints were overall survival and cost of the treatment. In all, 342 patients were included: 71 in the WBD cohort and 271 in the FD cohort. 201 patients (59.6%) experienced an irAE, and 24 of these events were graded as ≥3. At 12 months, there was no significant difference in irAE occurrence between the two cohorts [hazard ratio (95% confidence interval): 0.54 (0.21-1.36), P = 0.19]. The 12-month overall survival rate was significantly lower in the WBD cohort (P < 0.001). Switching from a fortnightly weight dose to a fixed monthly dose halves the cost of hospitalization. Our results did not show a significant difference between WBD and FD cohort in the occurrence of severe irAEs. However Overall survival appeared to be significantly higher in FD group. Some clinical trials are investigating a hybrid dosing regimen in which a WBD is capped by an FD. The present results need to be confirmed in prospective studies.

Targeting CCR4 with mogamulizumab in refractory CD3-CD4+ lymphocytic-variant hypereosinophilic syndrome.

Not available.

Evaluation of cancer drug infusion devices prior to the implementation of a compounding robot.

INTRODUCTION: Compounding robots are increasingly being implemented in hospital pharmacies. In our hospital, the recent acquisition of a robot (RIVATM, ARxIUM) for intravenous cancer drug compounding obliged us to replace the previously used infusion devices. The objective of the present study was to assess and qualify the new intravenous sets prior to their use in our hospital and prior to the implementation of the compounding robot. MATERIALS AND METHODS: The ChemoLockTM (ICU Medical) was compared with the devices used previously for compounding (BD PhaSealTM, Becton-Dickinson) and infusion (Connect-ZTM, Codan Medical). The connection/disconnection of infusion devices to/from 50 mL infusion bags was tested with a dynamometer (Multitest-i, Mecmesin). Leakage contamination was visualized by a methylene blue assay and was quantified in simulated pump infusions with 20 mg/mL quinine sulfate (N = 36/group); after the analytical assay had been validated, quinine was detected by UV-spectrophotometry at 280 and 330 nm. Groups were compared using chi-squared or Mann-Whitney U tests. RESULTS: The connection/disconnection test showed that although all the devices complied with the current standard, there was a statistically significant difference in the mean ± standard deviation compression force (51.5 ± 11.6 for the Connect-ZTM vs. 60.3 ± 11.7 for the ChemoLockTM; p = 0.0005). Leaks were detected in 32 (29.1%) of the 110 tests of the ChemoLockTM. The contamination rates were also significantly different: 13.9% for the BD PhaSealTM versus 75.0% for the ChemoLockTM; p < 0.0001). DISCUSSION/CONCLUSION: Our results showed that the new infusion device complied with current standards. However, the presence of contamination emphasizes the need for operators to use the recommended personal protective equipment. Further studies of contamination with cancer drugs are required.

[Robotic production of injectable anticancer drugs in hospital pharmacies]. / Production robotisée des préparations d'anticancéreux injectables en pharmacie hospitalière.

INTRODUCTION: Following the 2005 decree on securing the medicine supply chain, the production of "chemotherapies", anticancer drugs (cytotoxic, cytostatic, immunotherapy), was centralised within hospital pharmacies. To cope with increasingly growing activities, pharmacies are moving towards robotisation. This work offers feedback from four French sites pioneers in robotic production. MATERIAL AND METHOD: A review of the literature was carried out on the PubMed and Google Scholar scientific databases and GERPAC publications relating to the robotic production of chemotherapy preparations. This review allowed to select 25 articles. RESULTS: The robotisation of the production of "chemotherapies" requires infrastructural prerequisites, a reengineering of the manufacturing process and the patient journey. This impacts all the parties involved in this complex process. The "cobotisation" concept or collaborative robotics must be anticipated by the teams. Robotisation is an institutional decision, which must be owned by the pharmaceutical team and endorsed by the medical team and management. DISCUSSION/CONCLUSION: For reasons of optimisation, safeguarding and management of human resources, a large number of centres get equipped with robotic systems. Robotic preparation should extend to other non-hazardous preparation, as it is already the case in other countries. This strategic view should be carried out today to anticipate problems, ensure safety and improve the healthcare quality.

Perception, knowledge, practices and training regarding the risk of exposure to antineoplastic drugs in three French compounding units.

INTRODUCTION: Healthcare workers are exposed to hazardous drugs such as antineoplastic drugs, which have potential carcinogenic, mutagenic and teratogenic effects. Protective measures must be taken after appropriate staff training to handle antineoplastic drugs in a safe way. The objective was to assess perception, knowledge, practices and training regarding the risk of exposure of healthcare workers in three French compounding units. METHODS: This descriptive study was based on a questionnaire made of 33 questions divided into five sections related to the handling of antineoplastic drugs: perception of the risks, knowledge of the risks, protection practices, specific training and general questions. RESULTS: Among the 39 participants, over half considered their overall risk of exposure to antineoplastic drugs not being very low. Inhalation was known to 69.2% of them as possible route of contamination. The breakroom was identified by 28.9% of them as a place of contamination. The procedure in case of accidental exposure to antineoplastic drugs was known by 69.2%, but only half could explain it. Only 38.5% said they changed their gloves every 30 min as recommended. Barely half said that they had been trained specifically for the handling of antineoplastic drugs during an initial training. Over half wished to be informed, trained and aware of the proper handling of antineoplastic drugs. CONCLUSION: Although some of these results are encouraging, specifically when compared to the other settings where antineoplastic drugs are handled, there is still room for improvement. Efforts to build an adapted and impactful training program must pursue. CLINICAL TRIAL REGISTRATION: Study CONTACT, ref. 19-504.

Four-year follow-up of surface contamination by antineoplastic drugs in a compounding unit.

OBJECTIVES: This study aimed to monitor the contamination by antineoplastic drugs on work surfaces in a compounding unit 4 years after its implementation. METHODS: This descriptive study was done in a unit performing on average 45 000 preparations per year. Surface sampling points (N=23) were monitored monthly in the frame of routine activity from the opening of an anticancer drug compounding unit. Contamination with nine antineoplastic drugs (cyclophosphamide, ifosfamide, dacarbazine, 5-fluorouracil, methotrexate, gemcitabine, cytarabine, irinotecan and doxorubicin) was assessed on wipes with a local liquid chromatography coupled with a tandem mass spectrometer analysis. The contamination rate (CR, %) was prospectively monitored every month during the entire study period. The occurrence of critical incidents was also registered. The effect of each safety measure implemented during this period was also analysed. RESULTS: Based on the 1104 samples collected between March 2016 and March 2020, the CR was 18.5%. If three different critical incidents among a vial breakage that occurred were individually considered, this CR was slightly lower than that in the literature. Eight months after opening and taking different corrective actions, the overall CR dropped from 42.39% to 11.52% (p<0.001). Contamination was limited to the area that includes the compounding room and, more precisely, the welder and the QC-Prep+ sampling points. CONCLUSIONS: From the beginning of the study and from month to month, surface contamination was limited to the nearest sampling points to the compounding unit. This 4-year monitoring study allowed us to determine the intravenous conventional antineoplastic drugs and sampling points to be focused on.

Knowledge and practices about safe handling regarding the risk of exposure to antineoplastic drugs for caregivers in compounding units and in operating rooms performing HIPEC/PIPAC.

INTRODUCTION: Ever since the late 1970s, occupational exposure associated with the handling of antineoplastic drugs (ADs) in the healthcare environment has been highlighted and demonstrated. Contamination was detected in both operating rooms (OR) and compounding units (CU), where healthcare workers handle and are exposed to ADs in different ways. In the OR, the risk of exposure is higher and the staff receives less training in handling ADs than in the CU. This study aimed to assess and compare knowledge and practices about the safe handling of ADs by caregivers working in these two locations, namely the CU and OR. METHODS: Two questionnaires (one each for the OR and CU) were created by two investigator pharmacists and were completed during a personal interview of 20 min. The questions were related to the following topics: training, knowledge about occupational exposure and questions related to protective practices. A scoring system was implemented to assess the knowledge and practices of each participant. RESULTS: In total, 38 caregivers working in the OR and 39 in the CU were included in our study. Significantly more CU staff had specific initial training (p < 0.001) and ongoing training (p < 0.001) in handling ADs. Concerning the knowledge score, OR caregivers had a significantly lower median score for contamination routes (p < 0.001), contamination surfaces (p < 0.001), existing procedures (p < 0.001) and total knowledge (p < 0.001) than CU caregivers. Concerning protective handling practices of ADs, the two locations had nonsignificantly different median scores (p = 0.892). CONCLUSION: This study suggests that there is still room for improvement in terms of knowledge and protection practices when handling ADs. An appropriate and tailored training program should be developed and provided to all caregivers who handle or come in contact with ADs.Clinical trial registrationStudy CONTACT, ref. 19-504.

Introducing Augmented Reality Technique to Enhance the Preparation Circuit of Injectable Chemotherapy Drugs.

Chemotherapy preparations are often complex and subject to a strict regulatory context. The existing control methods are often limited to Double Visual Control (DVC). In this paper, the preparation circuit of chemotherapy drugs is evaluated through data collection and statistical analysis in order to highlight the difficulties encountered. The results regarding preparation and control times and the number of task interruptions highlight the unreliability of the DVC and its impact on processing time. As a solution, we propose a decision support system "Smart Prep" based on Augmented Reality (AR), co-developed, and commercialized by the Faculty of Pharmacy of Lille, Ecole Centrale de Lille and the company Computer Engineering. This system allows the preparation of chemotherapy drugs according to a step-by-step mode, a traceability of the preparation steps and a reduction of tasks' interruptions.

Ethanol Exposure During the Intravenous Administration of Chemotherapeutic Drugs: An Analysis of Clinical Practice and a Literature Review.

PURPOSE: Injectable cytotoxics may be formulated with ethanol. This study sought to quantify the amount of ethanol exposure during chemotherapy infusions. MATERIALS AND METHODS: We first reviewed the antineoplastic drugs (Anatomical Therapeutic and Chemical code L01) and oncologic supportive care drugs (eg, antiemetics) currently available in France, to identify preparations containing ethanol. The amount of ethanol in the final chemotherapy preparation was calculated. Next, we performed a 2-year, single-center, retrospective analysis of injectable antineoplastic drug compounding in routine clinical practice in a French university medical center. Finally, we reviewed our results with regard to the literature data. RESULTS: Ten of the 60 cytotoxic products on the market contained ethanol at concentrations of up to 790 mg/mL, depending on the drug, formulation, and supplier. Several final preparations contained more than 3 g of ethanol per infusion (the maximum recommended by the European Medicines Agency); this was notably the case for gemcitabine, paclitaxel (up to 20 g ethanol per injection, for both), and etoposide (up to 50 g ethanol per infusion). The analysis of our compounding activity showed that 3,172 (4.99%) of the 63,613 chemotherapy preparations (notably paclitaxel) contained more than 3 g of ethanol. None of the oncologic supportive care drugs contained ethanol. CONCLUSION: Patients are exposed to ethanol during the infusion of antineoplastic drugs. With a view to better patient care, physicians and pharmacists should carefully evaluate the risk of ethanol exposure throughout the course of cytotoxic drug treatment.

Fastidious chemical decontamination after cyclophosphamide vial breakage in a compounding unit.

An important amount of cytotoxic drug may accumulate in the workplace following the breakage of a vial containing an anticancer drug. Thanks to the monthly monitoring of the surface contamination in our compounding unit, a strong increase of cyclophosphamide contamination was highlighted in the storage area following the breakage of the vial, despite application of the emergency procedure. This study presents an analysis of chemical decontamination in the context of massive contamination. Samples were taken on the floor and on the caster of a storage shelf where the vial broke. The residual contamination was measured with a liquid chromatography-mass spectrometry/mass spectrometry method. An admixture of 10-2 M sodium dodecyl sulfate and 70% isopropanol (SDS/IPA 8:2) was selected as the decontamination solution. High amounts of cyclophosphamide were retrieved. The initial contamination on the floor was over 20 ng/cm2. Three decontaminations with SDS/IPA were carried out at Day 61, Day 68, and Day 71. The amount of cyclophosphamide decreased to 0.45 ng/cm2 at D134. However, high values were still measured on the caster despite successive decontaminations, with a maximal value of 19.78 ng/cm2 observed at Day 106. Continuous monitoring in our unit led us to highlight the inefficiency of our emergency procedure to eliminate high cyclophosphamide contamination. The procedure involving the SDS/IPA admixture was more efficient on the floor compared to the caster, which is a different surface type and porosity. This work highlights the importance of improving the procedures of incident management using contamination monitoring and repeated decontamination procedures adapted to different contaminants and surfaces.

A decontamination process adding a tensioactive agent and isopropanol to a closed-system drug transfer device for better control of isolator contamination. A prospective, parallel study.

BACKGROUND: Despite the use of closed system drug transfer devices (CSTD), residual contamination from antineoplastic drugs is still detected inside isolators. The aim of this study was to compare the decontamination level obtained using a CSTD + standard cleaning procedure with a CSTD + standard cleaning procedure + specific decontamination procedure. METHODS AND FINDINGS: A comparative and prospective study was carried out in a newly opened compounding unit. Compounding was performed with a CSTD (BD-Phaseal, Becton-Dickinson). In the Control isolator (C), the cleaning process was completed daily with a standard biocide solution (AnioxysprayTM, Anios, France). In the Intervention isolator (I), weekly decontamination with a homemade admixture of sodium dodecyl sulfate 10(-2) M/70% isopropanol (80/20, v/v) was added. Monitoring was performed via a validated LC-MS/MS method. Eight drugs (cyclophosphamide, cytarabine, dacarbazine, fluorouracile, gemcitabine, ifosfamide, irinotecan and methotrexate) were monitored daily over 14 consecutive weeks on three sites inside the isolators: gloves, workbench and window. Results are presented as the odds-ratio (OR) of contamination and as overall decontamination efficiency (EffQ, %). The proportion of EffQ ≥ 90% was assessed by a Fisher's exact test (p<0.05). Overall contamination rates (CR, %) were significantly different from one isolator to the other (CRC = 25.3% vs. CRI = 10.4%; OR = 0.341; p<0.0001). Overall EffQ values (median; 1st and 3rd quartiles) were higher in the intervention isolator (I: 78.3% [34.6%;92.6%] vs. C: 59.5% [-5.5%;72.6%]; p = 0.0015) as well as the proportion of days with an EffQ ≥ 90% (I: 42.9% vs. C: 7.1%; p = 0.077) but very variable depending on drugs. CONCLUSION: Adding a decontamination protocol with a tensioactive agent to a CSTD leads to better control of chemical contamination inside isolators. Improving decontamination by increasing decontamination frequency or modifying the protocol will be further studied.

Acute kidney injury after high dose etoposide phosphate: A retrospective study in children receiving an allogeneic hematopoetic stem cell transplantation.

BACKGROUND: Etoposide phosphate (EP; single injection, 60 mg/kg) followed by total body irradiation (TBI) at 12 Gy has been used as an allogeneic stem cell transplantation (allo-SCT) conditioning regimen for children since 2010. In our institution, EP has been suspected of leading to acute nephrotoxicity. The aim of this study was to assess the potential renal toxicity of EP in this context. MATERIALS AND METHODS: A retrospective study was carried out on children hospitalized between 2007 and 2015 for allo-SCT with TBI-based myeloablative conditioning associated with cyclophosphamide (CY, 60 mg/kg/day × 2 days) or EP. The primary endpoint of the study was the occurrence of acute kidney injury (AKI). Additional endpoints were time to recovery for children with AKI, survival, and treatment-related mortality. RESULTS: Thirty-five patients were analyzed (CY: 22 vs. EP: 13). AKI occurred more frequently in the EP group than in the CY one (69% vs. 27%, adjusted odds ratio 6.0, 95% confidence interval [CI] [1.145; 31.445], P = 0.03). The median time to recovery was estimated at 3 days, 95% CI (2; 17), with CY and 11 days 95% CI (5; 18) with EP (adjusted hazard ratio of recovery for EP vs. CY 0.262, 95% CI [0.071; 0.969], P = 0.04). No significant difference was highlighted between the two treatments for survival or for treatment-related mortality. DISCUSSION: This study shows that EP at high dosage or one of its excipients is probably responsible for AKI, as compared to CY. Further studies are required to explore the origin of this adverse effect.

Rôle du pharmacien hospitalier dans le circuit d'une catégorie de Médicament de Thérapie Innovante : les lymphocytes T exprimant un Récepteur Chimérique à l'Antigène.

ROLE OF THE HOSPITAL PHARMACIST IN THE MANAGEMENT OF A CATEGORY OF ADVANCED THERAPY MEDICINAL PRODUCT: CHIMERIC ANTIGEN RECEPTOR T-CELLS: Chimeric Antigen Receptor T-cells (CART) belongs to a new class of medicine, Advanced Therapy Medicinal Product, such as define by the European Regulation 1394/2007, and more exactly to the category of gene therapy medicinal product. Their status of medicine, as well as genetically modified organisms, imposes a particular circuit at hospital while maintaining a way over the Hospital Pharmacy. The manipulation of genetically modified cells is not usual in pharmacy. It requires, besides the acquisition of new skills, a not insignificant reorganization of the teams and the rooms of the pharmacy as well as an adapted training of the staff. A good communication is essential between the various actors of the circuit. The hospital pharmacist plays a key role in the implementation of a circuit adapted to this new type of medicine. This article aims to identify the roles of the hospital pharmacist and more generally of the pharmacy in the management of CART. We shall detail the specificities of this type of medicine in every stage of the circuit and the adaptations necessary to realize to guarantee the quality and the safety of the treatment by CART. Beyond the implementation of the circuit in the hospital, the pharmacist has an important role to be played in the follow-up of the patients after administration in view of the complexity of the side effects and a certain role in the training of the teams to this new medicine. Cet article fait partie du numéro supplément Les cellules CAR-T : une révolution thérapeutique ? réalisé avec le soutien institutionnel des partenaires Gilead : Kite et Celgene.

Evaluation of Specific Administering Devices for Antineoplastic Drugs Compounded in Syringes in Paediatry: Methodology Proposal.

Purpose The aims of this study were to propose a simple methodology to assess the rinsing volume of syringe extension sets and to compare several marketed devices. Methods A UV-spectrophotometry assay using quinine hydrochloride as drug substitute was developed. Quinine concentration ranged from 20 to 200 µg/ml. The assay was validated with the accuracy profile method and tested on five different assemblies (device+extension sets) with different dead-space volumes (1.28-2.80 ml) and at two different quinine concentrations (0.3 and 8.0 mg/ml). Rinsing was performed stepwise with water for injection until reaching an undetectable quinine concentration. After fitting the data with a Weibull model, assemblies were compared with an ANOVA performed on ranks (GraphPad, La Jolla, USA). Results The within-day and between-day precision ranges were 0.39-0.81 and 0.48-0.84%, respectively. The lower limit of quantification was 4.26 µg/ml. The volume required to completely rinse the infusion line was different according to the initial drug concentration and to the device assessed: from 6 to 10 ml for a low quinine concentration and from 7 to 17 ml for a high quinine concentration. Conclusion This study shows that a simple, cheap and easy-to-use methodology may be used to assess the rinsing volume of syringe extension sets. The rinsing volume is different according to the tested device.

Effectiveness of a Closed-System Transfer Device in Reducing Surface Contamination in a New Antineoplastic Drug-Compounding Unit: A Prospective, Controlled, Parallel Study.

BACKGROUND: The objective of this randomized, prospective and controlled study was to investigate the ability of a closed-system transfer device (CSTD; BD-Phaseal) to reduce the occupational exposure of two isolators to 10 cytotoxic drugs and compare to standard compounding devices. METHODS AND FINDINGS: The 6-month study started with the opening of a new compounding unit. Two isolators were set up with 2 workstations each, one to compound with standard devices (needles and spikes) and the other using the Phaseal system. Drugs were alternatively compounded in each isolator. Sampling involved wiping three surfaces (gloves, window, worktop), before and after a cleaning process. Exposure to ten antineoplastic drugs (cyclophosphamide, ifosfamide, dacarbazine, 5-FU, methotrexate, gemcitabine, cytarabine, irinotecan, doxorubicine and ganciclovir) was assessed on wipes by LC-MS/MS analysis. Contamination rates were compared using a Chi2 test and drug amounts by a Mann-Whitney test. Significance was defined for p<0.05. Overall contamination was lower in the "Phaseal" isolator than in the "Standard" isolator (12.24% vs. 26.39%; p < 0.0001) although it differed according to drug. Indeed, the contamination rates of gemcitabine were 49.3 and 43.4% (NS) for the Standard and Phaseal isolators, respectively, whereas for ganciclovir, they were 54.2 and 2.8% (p<0.0001). Gemcitabine amounts were 220.6 and 283.6 ng for the Standard and Phaseal isolators (NS), and ganciclovir amounts were 179.9 and 2.4 ng (p<0.0001). CONCLUSION: This study confirms that using a CSTD may significantly decrease the chemical contamination of barrier isolators compared to standard devices for some drugs, although it does not eliminate contamination totally.

Potential Impact of Infusion Technique on Drug Delivery.

BACKGROUND: Infusion practices have been modified, especially for antineoplastic drugs, through the use of specific infusion devices with postadministration rinsing (PAR) so as to decrease occupational exposure to drugs. The aim of this study was to highlight how such infusion devices may impact the drug delivery of injectable drugs. MATERIALS AND METHODS: Drug infusions were simulated with a radiotracer (99mTc) for 30 minutes to assess nine different infusion lines: 2 infusion methods without PAR (1 gravity-fed infusion and 1 pump infusion), 2 extension lines to be connected to standard infusion devices to allow PAR, and 5 specific infusion sets allowing a PAR. 99mTc was compounded in 250 or 100 mL of 0.9% NaCl solution. From the continuous recording of drug concentrations at device outlets, the areas under the drug concentration-time curve (AUC) were computed and divided in 2 parts: the AUCadm corresponding to the administration phase and the AUCrin corresponding to the rinsing phase. Their comparison to the initial activity led to compute the drug delivery. Results between groups were compared using a Kruskal-Wallis test (P < 0.05). RESULTS: Using standard infusion devices leads to administer only 91% and 88% when the drug is diluted in 250 and 100 mL, respectively. During the administration phase with the extension lines connected to infusion sets, between 90.8 ± 6.9% and 94.2 ± 1.8% of the drug is infused for 250 mL dilutions and 87.7 ± 2.0% for 100 mL dilutions. For specific infusion sets, the proportion of infused drug varied between 88.6 ± 6.0% and 95.3 ± 1.5% for dilutions in 250 mL and 71.2 ± 3.1% and 90.4 ± 2.8% for dilutions in 100 mL. Rinsing the lines means the remaining drug is administered a rinsing volume ranging between 47.0 ± 6.6 and 92.2 ± 8.9 mL according to the device and drug dilution. CONCLUSIONS: This study shows that drug delivery may differ according to infusion line and dilution volume. Further study is required to assess the impact of these devices on pharmacokinetics.

Influence of infusion method on gemcitabine pharmacokinetics: a controlled randomized multicenter trial.

PURPOSE: Ensuring the correct administration of antineoplastic drugs is a constantly challenging task. Nowadays, several specific infusion devices have been marketed to decrease occupational exposure to these drugs through a post-administration rinsing step. As their impact on drug pharmacokinetics has never been evaluated, the objective of this study was to assess how the infusion process may alter the pharmacokinetics of antineoplastic drugs. METHODS: We developed a prospective randomized multicenter pharmacokinetic study (ONCOPERF01) to compare the influence of three infusion techniques (gravity-fed infusion-GFI, infusion pump-IP, and gravity-fed infusion with post-administration rinsing-PAR) to assess the impact of both flow rate and post-administration rinsing on gemcitabine pharmacokinetics during three consecutive administrations. Gemcitabine pharmacokinetics was determined with a two-compartment model after plasma dosing with an HPLC-UV method. Statistical comparisons of the three groups were made using repeated-measure analysis of variance (PROC MIXED). RESULTS: Patients received gemcitabine by gravity-fed infusion (GFI, n = 9; IP, n = 9; PAR, n = 7). Significant differences were noted between infusion duration (GFI = 30.0 ± 2.6 min, IP = 29.1 ± 1.2 min, PAR = 33.7 ± 3.5 min; p = 0.003) and AUCt (GFI = 23.5 ± 8.2 µM h, IP = 25.4 ± 9.1 µM h, PAR = 28.5 ± 6.3 µM h; p = 0.0009), which was significantly higher in the infusion group with post-administration rinsing than in the other groups. CONCLUSIONS: The ONCOPERF01 study indicates that post-administration rinsing leads to a significant increase in patient exposure to gemcitabine, whereas controlling flow rate has no significance. Further surveys are required to assess the impact of such infusion techniques on other antineoplastic drugs.