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European Journal of Cancer (Oxford,... Mar 2022Cancer in neonates and infants is a rare but challenging entity. Treatment is complicated by marked physiological changes during the first year of life, excess rates of... (Review)
Review
Cancer in neonates and infants is a rare but challenging entity. Treatment is complicated by marked physiological changes during the first year of life, excess rates of toxicity, mortality, and late effects. Dose optimisation of chemotherapeutics may be an important step to improving outcomes. Body size-based dosing is used for most anticancer drugs used in infants. However, dose regimens are generally not evidence based, and dosing strategies are frequently inconsistent between tumour types and treatment protocols. In this review, we collate available pharmacological evidence supporting dosing regimens in infants for a wide range of cytotoxic drugs. A systematic review was conducted, and available data ranked by a level of evidence (1-5) and a grade of recommendation (A-D) provided on a consensus basis, with recommended dosing approaches indicated as appropriate. For 9 of 29 drugs (busulfan, carboplatin, cyclophosphamide, daunorubicin, etoposide, fludarabine, isotretinoin, melphalan and vincristine), grade A was scored, indicating sufficient pharmacological evidence to recommend a dosing algorithm for infants. For busulfan and carboplatin, sufficient data were available to recommend therapeutic drug monitoring in infants. For eight drugs (actinomycin D, blinatumomab, dinutuximab, doxorubicin, mercaptopurine, pegaspargase, thioguanine and topotecan), some pharmacological evidence was available to guide dosing (graded as B). For the remaining drugs, including commonly used agents such as cisplatin, cytarabine, ifosfamide, and methotrexate, pharmacological evidence for dosing in infants was limited or non-existent: grades C and D were scored for 10 and 2 drugs, respectively. The review provides clinically relevant evidence-based dosing guidance for cytotoxic drugs in neonates and infants.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carboplatin; Etoposide; Humans; Infant; Infant, Newborn
PubMed: 34865945
DOI: 10.1016/j.ejca.2021.11.001 -
Journal of Pediatric Oncology Nursing :... 2021Immunotherapy is a new and promising approach to treating pediatric cancers. These types of therapies have unique mechanisms of action for identifying and fighting...
BACKGROUND
Immunotherapy is a new and promising approach to treating pediatric cancers. These types of therapies have unique mechanisms of action for identifying and fighting cancer, as compared with traditional chemotherapy, and therefore are associated with different therapy-related adverse events (AEs). The purpose of this systematic review was to review available evidence to: (a) identify commonly reported AEs associated with immunotherapy agents frequently used in pediatric oncology and (b) generate recommendations for nursing practice.
METHOD
A clinical question was developed and used to guide the systematic literature review. Five immunotherapy agents (dinutuximab, blinatumomab, rituximab, inotuzumab ozogamicin, brentuximab vedotin) were selected for inclusion secondary to their high relevance to pediatric oncology. A literature search was conducted to locate articles published between January 1, 2003 and October 31, 2018.
RESULTS
Seventeen articles met eligibility criteria for inclusion and were evaluated using the Grading of Recommendations Assessment, Development, and Evaluation criteria. The most commonly reported AEs for the selected immunotherapy agents were identified and summarized. Strong recommendations are made for nurses to become familiar with the unique AE profiles associated with individual immunotherapy agents. Agent-specific recommendations for nursing practice regarding AEs associated with dinutuximab and rituximab were generated.
CONCLUSIONS
Immunotherapy is rapidly emerging as an effective therapy for pediatric cancers. Nurses need to be aware of the breadth of agent-specific, immunotherapy-related AEs to appropriately monitor and manage patients receiving these therapies. Additional work is needed to confidently profile immunotherapy-related AEs in pediatric oncology and to develop agent-specific educational materials for patients/families.
Topics: Child; Humans; Immunotherapy; Medical Oncology; Neoplasms
PubMed: 33111626
DOI: 10.1177/1043454220966590 -
The Cochrane Database of Systematic... Apr 2019Neuroblastoma is a rare malignant disease that primarily affects children. The tumours mainly develop in the adrenal medullary tissue, and an abdominal mass is the most...
Anti-GD2 antibody-containing immunotherapy postconsolidation therapy for people with high-risk neuroblastoma treated with autologous haematopoietic stem cell transplantation.
BACKGROUND
Neuroblastoma is a rare malignant disease that primarily affects children. The tumours mainly develop in the adrenal medullary tissue, and an abdominal mass is the most common presentation. High-risk disease is characterised by metastasis and other primary tumour characteristics resulting in increased risk for an adverse outcome. The GD2 carbohydrate antigen is expressed on the cell surface of neuroblastoma tumour cells and is thus a promising target for anti-GD2 antibody-containing immunotherapy.
OBJECTIVES
To assess the efficacy of anti-GD2 antibody-containing postconsolidation immunotherapy after high-dose chemotherapy (HDCT) and autologous haematopoietic stem cell transplantation (HSCT) compared to standard therapy after HDCT and autologous HSCT in people with high-risk neuroblastoma. Our primary outcomes were overall survival and treatment-related mortality. Our secondary outcomes were progression-free survival, event-free survival, early toxicity, late non-haematological toxicity, and health-related quality of life.
SEARCH METHODS
We searched the electronic databases CENTRAL (2018, Issue 9), MEDLINE (PubMed), and Embase (Ovid) on 20 September 2018. We searched trial registries and conference proceedings on 28 October 2018. Further searches included reference lists of recent reviews and relevant articles as well as contacting experts in the field. There were no limits on publication year or language.
SELECTION CRITERIA
Randomised controlled trials evaluating anti-GD2 antibody-containing immunotherapy after HDCT and autologous HSCT in people with high-risk neuroblastoma.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, abstracted data on study and participant characteristics, and assessed risk of bias and GRADE. Any differences were resolved by discussion, with third-party arbitration unnecessary. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. We used the five GRADE considerations, that is study limitations, consistency of effect, imprecision, indirectness, and publication bias, to judge the quality of the evidence.
MAIN RESULTS
We identified one randomised controlled trial that included 226 people with high-risk neuroblastoma who were pre-treated with autologous HSCT. The study randomised 113 participants to receive immunotherapy including isotretinoin, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2, and ch14.18, a type of anti-GD2 antibody also known as dinutuximab. The study randomised another 113 participants to receive standard therapy including isotretinoin.The results on overall survival favoured the dinutuximab-containing immunotherapy group (hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31 to 0.80; P = 0.004). The results on event-free survival also favoured the dinutuximab-containing immunotherapy group (HR 0.61, 95% CI 0.41 to 0.92; P = 0.020). Randomised data on adverse events were not reported separately. The study did not report progression-free survival, late non-haematological toxicity, and health-related quality of life as separate endpoints. We graded the quality of the evidence as moderate.
AUTHORS' CONCLUSIONS
The evidence base favours dinutuximab-containing immunotherapy compared to standard therapy concerning overall survival and event-free survival in people with high-risk neuroblastoma pre-treated with autologous HSCT. Randomised data on adverse events are lacking, therefore more research is needed before definitive conclusions can be made regarding this outcome.
Topics: Antibodies, Monoclonal; Child; Consolidation Chemotherapy; Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors; Immunotherapy; Neuroblastoma; Randomized Controlled Trials as Topic
PubMed: 31016728
DOI: 10.1002/14651858.CD012442.pub2