Securing the oral and enteral oncopediatric chemotherapy process in pediatric oncology: Introduction of the ENFit™ standard in a controlled-atmosphere area and implementation of a dispensing service of medications to outpatients circuit with advice on proper use.

INTRODUCTION: Oral chemotherapies pediatrics are manufactured from injectable specialties in a controlled-atmosphere area. Packaged in Luer-Lock syringes, the transition to an ENFit™ connector became crucial to enable administration in surveyed patients. In parallel, a study was carried out to optimize and secure patient care by setting up a retrocession circuit. OBJECTIVE: To introduce the ENFit™ range of devices into the manufacturing process for oral or enteral chemotherapy syringes. Secondly, establish a retrocession circuit, validate its economic relevance and implement and evaluate efforts to promote proper use. METHODS: ENFit™ meeting the specifications were sourced and then evaluated. Research was conducted on the legislative framework governing the retrocession of masterful preparations made from injectable specialties. A 2021 retrospective economic study enabled the assessment of the financial balance generated by a potential retrocession circuit. Meetings to promote the good use of medication were conducted. Satisfaction questionnaires were created for caregivers and medical staff in the pediatric department. RESULTS: All ENFit™ ranges have been referenced within the Fresenius laboratory. Retrocession has been set up in accordance with legislation. The economic study highlighted a potential revenue of EUR 69,900 in 2021. Three good-use booklets and a dosage plan were created to promote good use. Ten families and 12 caregivers responded to the questionnaire, with satisfaction rates of 81.1% and 71.9%, respectively. CONCLUSION: ENFit™ devices has enabled oral and enteral administration of chemotherapy. The retrocession circuit includes all the good-use elements required for optimal patient care. The results of the satisfaction survey are positive, certain areas for improvement have been identified.

Impact of histamine-2 antagonist shortage on the incidence of hypersensitivity reactions to paclitaxel: a reconsideration of premedication protocols in France (PACLIREACT Study).

PURPOSE: An international shortage of ranitidine led to adjustments in premedication regimens for paclitaxel-based chemotherapy in early October 2019. In this study, we implemented and evaluated an anti-allergic protocol without histamine-2 antagonists (H2As) and aimed to assess the risk of hypersensitivity reactions (HSRs) to the different premedication regimens used. METHODS: We conducted a single-center observational retrospective study of paclitaxel administrations (7173 administrations in 831 patients). Between January 2019 and December 2020, all allergies reported were recorded. A mixed logistic regression model was implemented to predict the risk of allergy at each injection and to account for repeated administration per patient. RESULTS: A total of 27 HSRs occurred in 24 patients. No protective effect was observed for H2A when comparing paclitaxel injections with H2A premedication versus without H2A (OR = 1.12, p = 0.84). There was also no significant difference in risk of HSR for famotidine versus ranitidine (OR = 0.79, p = 0.78). However, the risk of HSRs was significantly lower for paclitaxel injections with corticosteroids than for those without (OR = 0.08, p = 0.03). In addition, the risk of HSR was significantly higher for the first, second, or third paclitaxel injections than for the subsequent injections (OR = 10.1, p < 0.001). CONCLUSION: We did not find substantial evidence of an increased risk of HSR due to the absence of H2A in the premedication protocols for paclitaxel. Thus, in contrary to the existing literature on paclitaxel, our findings support the use of a premedication protocol without H2A.

Successful administration of mitotane (O, p'-DDD) in pediatric oncology.

INTRODUCTION: Mitotane (o, p'-DDD) is a molecule that was developed many years ago for adrenal cortical carcinoma, but no suitable pediatric dosage form is available for administration to young children. Mitotane requires therapeutic drug monitoring because of its long half-life and difficulty in stabilizing plasma concentrations. Furthermore, Mitotane is a highly lipophilic drug that requires concurrent lipid administration. CASE REPORT: We present the case of a 3-year-old girl who was diagnosed with metastatic adrenal cortical carcinoma. Due to the difficulty in administering the tablets and the non-stabilized mitotane dosages, a nasogastric tube was inserted. An administration protocol based on dispersing the tablets in whole milk was established by the pharmacy team. This led to the stabilization of the disease for at least 1.5 years. MANAGEMENT AND OUTCOME: Mitotanemia is difficult to stabilize even when treatment is administered orally. To maintain biological efficacy, we propose an easily reproducible protocol. The efficacy was stabilized at a dosage of 1500 mg per day. Mitotanemia fluctuated between 14 mg/mL, and 20 mg/mL. The implementation of this protocol prevented treatment discontinuation. DISCUSSION: The administration of narrow therapeutic range drugs via a nasogastric tube is a challenge for healthcare teams, particularly in pediatric patients. Based on the findings of this clinical case, clinicians should consider future use of this protocol. The use of whole milk as a vehicle for mitotane is a simple, effective, and reproducible method to administer the drug to pediatric patients and can be used for other similar cases.

Advantages of everolimus therapeutic drug monitoring in oncology when drug-drug interaction is suspected: A case report.

INTRODUCTION: Drug interactions involving everolimus are fairly well known because of its common use, primarily as an immunosuppressant. Several recommendations regarding therapeutic drug monitoring are also available for the use of everolimus-based immunosuppression regimens. However, everolimus use in oncology differs substantially, particularly because of the high doses involved. Therapeutic drug monitoring, although sometimes necessary, is not recommended as a routine in oncology. Thus, it was deemed inapplicable due to the lack of clear recommendations. CASE REPORT: Here, we present a case where a patient was prescribed everolimus for renal cell carcinoma. The patient benefitted from a pharmaceutical consultation prior to treatment initiation, and a drug interaction with verapamil was suspected.Management and outcome: Therapeutic drug monitoring of everolimus was proposed. Based on the everolimus values reported in the literature, trough plasma concentration in the patient was greatly increased. The patient was then diagnosed with grade 4 oral mucositis, thereby requiring temporary suspension of everolimus treatment. Management of adverse effects was performed through multiple medicated mouthwashes. DISCUSSION: Therapeutic drug monitoring for everolimus is important for potential drug interactions or the occurrence of severe adverse events. In such cases, dose adjustments should be managed according to everolimus plasma concentrations. Clear oncological recommendations regarding plasma everolimus thresholds are required for a successful follow-up of the patient's condition and to ensure adequate response to treatment.

[Incidence and risk factors for ifosfamide-related encephalopathy in sarcoma patients]. / Incidence et facteurs de risque de l'encéphalopathie à l'ifosfamide chez les patients suivis pour un sarcome.

CONTEXT: Ifosfamide remains one of the major cytotoxic drugs for sarcoma management. Ifosfamid-related encephalopathy (IRE) is a rare but severe adverse event, without clearly identified risk factors. METHOD: We have carried out a single-center, retrospective study to assess the occurrence and the risk factors for IRE after the two first cycles of chemotherapy. We have collected the data-describing patients, biological data, tumors characteristics (histology, leptomeningeal metastasis) and ifosfamide administration modalities. RESULTS: From September 2008 to November 2013, we have identified 8 IRE out of 187 patients (4.2% [CI95%: 1.8-8.2]). The median age was 27 (0-78). Histologies were adult soft tissue sarcomas (78 patients), osteosarcoma (48), ewing sarcoma (41) and rhabdomyosarcoma (26). Most of factors were not associated with IRE. Only 8 patients have received aprepitant, none of them experienced IRE. Under univariate analysis, the risk factors for IRE were: PS≥2 (OR=9.52 [CI95%: 2.38-38.80]), albumin≤36g/L (OR=9.79 [CI95%: 1.19-80.26]), leptomeningeal metastasis (OR=13.20 [CI95%: 2.76-63.19]), 4 or 5 successive days of ifosfamide administration (OR=6.00 [CI95%: 1.40-25.60]). Under multivariate analysis, the risk factors for IE were: PS≥2 (OR=16.00 [IC95%: 2.80-67.00]), leptomeningial metastasis (OR=23.56 [IC95%: 2.01-456.80]) and 4 or 5 days of ifosfamide administration (OR=57.45 [IC95%: 1.66-35.00]). CONCLUSION: Ifosfamide administration must be given with caution in patients with poor performans status. A 4 to 5 days fractioned ifosfamide and leptomeningeal metastasis seems associated with increased risk for IRE, whatever the total administered dose.

Securing the circuit of intrathecally administered cancer drugs: example of a collective approach.

The treatment of leptomeningeal metastasis is based on protocols linking systemic chemotherapies and intrathecal injections of antineoplastic agents. Since the late 1960s, cases of accidental intrathecal injections of vinca-alkaloids, which have almost always proved fatal, have been documented. The most concerned countries, supported by the WHO, have published numerous recommendations aimed at reducing this type of risk. The aim of our work was to improve safety procedures for the intrathecal administration of antineoplastic drugs in an oncology hospital: the Centre Oscar Lambret, Lille, France. To this end, we compiled and analyzed a total of eight international recommendations. Our method was to meet the requirements of the AFSSAPS (French agency for the safety of health products), then to adopt recommended procedures in other countries, where appropriate. We considered the whole drugs circuit from prescription to administration. Improvements basically focused on the computerization of prescription, the dilution in mini-bags of vinca-alkaloids, and the additional labeling of intrathecally administered preparations as well as those with some vinca-alkaloids. This multidisciplinary approach to improve our practices complements the precautions taken by healthcare teams.