Purpose-Surface contamination with the antineoplastic drugs cyclophosphamide, ifosfamide, and 5-fluorouracil was compared in 22 US hospital pharmacies following preparation with standard drug preparation techniques or the PhaSeal ® closed-system drug transfer device (CSTD).Methods-Wipe samples were taken from biological safety cabinet (BSC) surfaces, BSC airfoils, floors in front of BSCs, and counters and analyzed for contamination with cyclophosphamide, ifosfamide, and 5-fluorouracil. Contamination was reassessed several months after the implementation of the CSTD. Surface contamination (ng/cm 2 ) was compared between the two techniques and evaluated with the Signed Rank Test.Results-Using the CSTD compared to the standard preparation techniques, a significant reduction in levels of contamination was observed for all drugs (cyclophosphamide: p <0.0001; ifosfamide: p <0.001; 5-fluorouracil: p <0.01). Median values for surface contamination with cyclophosphamide, ifosfamide, and 5-fluorouracil were reduced by 95%, 90%, and 65%, respectively.Conclusions-Use of the CSTD significantly reduces surface contamination when preparing cyclophosphamide, ifosfamide, and 5-fluorouracil as compared to standard drug preparation techniques.Reprints and permissions: sagepub.co.uk/journalsPermissions.nav Corresponding author: Dr. Paul J.M. Sessink, Exposure Control B.V.,

Exploiting the antitumor effect of natural killer (NK) cells has regained interest in light of data from preclinical and clinical work on the potential of alloreactive NK cells. Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) represent the two most prevalent adult hematological malignancies in the western hemisphere. To evaluate the role of NK cells in the immune surveillance and their therapeutic potential for CLL and MM, tumor cell susceptibility to NK-mediated killing was investigated. Results show relative resistance of tumor cells from CLL as well as MM (73 and 70% of the patients, respectively) to NK-mediated killing. To gain insight into molecular mechanisms of this resistance, the expression of the tolerogenic HLA-G molecule in CLL and MM and its relevance to susceptibility to NK-mediated killing were investigated. HLA-G transcript was found in tumor cells from 89% (n ¼ 19) of CLL and 100% (n ¼ 9) of MM patients examined. HLA-G1 surface expression was observed in CLL and was very low or undetectable in MM. Notably, blocking of HLA-G1 with specific antibody on CLL samples increased their susceptibility to NK-mediated killing, demonstrating that HLA-G participates in protecting CLL cells from NK-mediated killing and may thus contribute to their immune escape in vivo.

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A study involving a rigorous protocol and 13 cancer centers across the United States demonstrated that the CSTD reduced surface contamination by cyclophosphamide and fluorouracil during compounding and simulated administration. Participants reported that the CSTD was easy to use.

Dasatinib 100 mg once daily has a more favorable risk to benefit assessment compared with the previous 70 mg twice-daily regimen and is now the recommended schedule for patients with CP CML.

Since 1955, the only available H 1 antihistamines for intravenous administration have been first-generation formulations and, of those, only intravenously administered (IV) diphenhydramine is still approved in the USA. Orally administered cetirizine hydrochloride, a second-generation H 1 antihistamine, has been safely used over-the-counter for many years. In 2019, IV cetirizine was approved for the treatment of acute urticaria. In light of this approval, this narrative review discusses the changing landscape of IV antihistamines for the treatment of histamine-mediated conditions. Specifically, IV antihistamines will be discussed as a treatment option for acute urticaria and angioedema, as premedication to prevent infusion reactions related to anticancer agents and other biologics, and as an adjunct treatment for anaphylaxis and other allergic reactions. Before the development of IV cetirizine, randomized controlled trials of IV antihistamines for these indications were lacking. Three randomized controlled trials have been conducted with IV cetirizine versus IV diphenhydramine in the ambulatory care setting. A phase 3 trial of IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 262 adults who presented to the urgent care/emergency department with acute urticaria requiring antihistamines. For the primary efficacy endpoint, defined as change from baseline in a 2-h patient-rated pruritus score, non-inferiority of IV cetirizine to IV diphenhydramine was demonstrated (score − 1.6 vs − 1.5, respectively; 95% CI − 0.1, 0.3). Compared with IV diphenhydramine, IV cetirizine demonstrated fewer adverse effects including less sedation, a significantly shorter length of stay in the treatment center, and fewer returns to the treatment center at 24 and 48 h. Similar findings were demonstrated in another phase 2 acute urticaria trial and in a phase 2 trial assessing IV cetirizine for pretreatment for infusion reactions in the oncology/immunology setting. IV cetirizine is associated with similar patient outcomes, fewer adverse effects, and increased treatment center efficiency than IV diphenhydramine.

Oral NEPA is the fixed‐combination antiemetic comprising netupitant (neurokinin‐1 receptor antagonist [NK1RA]) and palonosetron (5‐hydroxytryptamine‐3 receptor antagonist [5‐HT3 RA]). Intravenous (IV) NEPA, containing fosnetupitant, a water‐soluble N‐phosphoryloxymethyl prodrug of netupitant, has been developed. Fosnetupitant does not require excipients or solubility enhancers often used to increase IV NK1RA water solubility, preventing the occurrence of hypersensitivity and infusion‐site reactions associated with these products. In this phase 1 study, subjects received a 30‐minute placebo or fosnetupitant (17.6–353 mg) infusion and an oral NEPA or placebo capsule, with 2‐sequence crossover treatment for fosnetupitant 118‐ to 353‐mg dose cohorts. IV fosnetupitant safety and pharmacokinetics were evaluated, and its equivalence to an oral netupitant 300‐mg dose was defined. Overall, 158 healthy volunteers were enrolled. All adverse events (AEs) were mild or moderate in intensity. Doppler‐identified infusion‐site asymptomatic thrombosis occurred in 5.4% (fosnetupitant) and 1.2% (oral NEPA) of subjects. The frequency or number of treatment‐related AEs did not increase with ascending fosnetupitant doses. The most common treatment‐related AEs were headache (fosnetupitant, 8.1%; oral NEPA, 12.7%) and constipation (fosnetupitant, 1.4%; oral NEPA, 7.5%). A fosnetupitant 235‐mg dose was equivalent, in terms of netupitant exposure, to 300‐mg oral netupitant. The safety profile of a single fosnetupitant 235‐mg infusion was similar to that of single‐dose oral NEPA.

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