RESUMO
INTRODUCTION: Venetoclax (VEN), a selective BCL2 inhibitor, has single-agent activity in relapsed and refractory (R/R) acute myeloid leukemia (AML), and efficacy in lower intensity combinations for treatment-naïve elderly AML patients. VEN treatment combinations in R/R AML have not been previously reported. METHODS: All R/R myeloid patients (including AML, myelodysplastic syndrome (MDS), and blastic plasmacytoid dendritic cell neoplasm (BPDCN)) treated with VEN combinations in the salvage setting were reviewed. RESULTS: Forty-three patients with median age 68 (range, 25-83) were treated for AML (91%), MDS (5%), or BPDCN (5%). Most (n = 36, 84%) were ≥ salvage-2 treatment status, including prior hypomethylating agent (HMA) in 77%. In combination with VEN, most patients received HMA therapy (n = 31, 72%); eight (19%) received low-dose cytarabine (LDAC). Patients received a median of 2 treatment cycles (range, 1-4). Objective response was observed in 9 (21%) patients, including 2 complete responses (CR), 3 CRi, and 4 morphologic leukemia-free state (MLFS). Median survival was 3.0 months (range, 0.5-8.0), and estimated 6-month survival was 24%. Responses were observed in five (24%) of 21 patients with intermediate-risk cytogenetics, 3 (27%) of 11 IDH1/2-mutant, and 4 (50%) of 8 RUNX1-mutated patients. Two (20%) of 10 TP53-mutated patients responded; both had concurrent RUNX1 mutations. Of the 3 (15%) responding patients with adverse cytogenetics, all had concurrent RUNX1 mutations. CONCLUSION: Low-intensity chemotherapy, including HMAs or LDAC, in combination with VEN is a viable salvage option, even in multiply relapsed/refractory patients with AML, MDS, and BPDCN. Notable responses were identified in patients with diploid/intermediate cytogenetics, RUNX1, and/or IDH1/2 mutations.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Terapia de Alvo Molecular , Síndromes Mielodisplásicas/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Terapia de Salvação , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Células Dendríticas , Feminino , Genes p53 , Humanos , Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Recidiva , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologiaRESUMO
PURPOSE: GI medical oncology care presents unique medication challenges. Here, we captured our clinical pharmacy specialists' (CPSs) involvement in patients with GI cancers starting cycle 1 of a new treatment. METHODS: Our quality initiative was performed in three stages (preintervention, intervention, and postintervention). Preintervention: retrospective baseline data collection from May to December 2019. Intervention: one-time telephone encounters were conducted by a CPS between March 15 and June 11, 2021. The primary objective of the quality improvement initiative was to increase patient interaction with a CPS to 80%. Postintervention: data collection to review the impact of CPS telephone encounters. RESULTS: Preintervention: we reviewed the electronic health records of 262 patients. Sixty nine percent of patients reported at least one adverse event (AE; range 1-6 AEs) at the first physician follow-up after treatment start. Most reported AEs (78%) were considered modifiable within the scope of CPS practice. Postintervention: during the intervention, 92% of patients (n = 389) received a telehealth encounter with the CPS. At the encounter, 315 patients (81%) reported at least one AE. CPS provided recommendations and/or additional education for 88% of reported AEs. Medication lists required correction 75% of the time. The median time for CPS encounters (including documentation) was 40 minutes. CONCLUSION: During a 3-month period, this quality improvement initiative successfully provided an early CPS-based telehealth intervention to identify and make initial recommendations for management of AEs for patients on cycle 1 of systemic therapy for GI cancer.
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Oncologia , Farmacêuticos , Telefone , Humanos , Masculino , Feminino , Oncologia/métodos , Pessoa de Meia-Idade , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/terapia , Estudos Retrospectivos , Idoso , Adulto , Seguimentos , Melhoria de QualidadeRESUMO
BACKGROUND: The World Health Organization classifies myelodysplastic syndromes (MDS) as a group of hematologic malignancies where at least one myeloid lineage contains ≥10% cells with myelodysplasia. Therapy-related MDS (t-MDS) may result from treatment with myelosuppressive chemotherapy and/or radiation. Myeloid growth factors, such as pegfilgrastim, have also been investigated as a possible risk factor for development of t-MDS. National guidelines and myeloid growth factor prescribing information recommend administering myeloid growth factors after a minimum of 24 h following myelosuppressive chemotherapy. Some evidence suggests that administering myeloid growth factors and myelosuppressive chemotherapy concurrently may increase the risk of developing t-MDS. OBJECTIVE: To evaluate the incidence of t-MDS in patients who received pegfilgrastim and chemotherapy on the same day compared to patients receiving pegfilgrastim at least 1 day following completion of their chemotherapy. METHODS: A retrospective chart review was performed to identify all patients who received myelosuppressive chemotherapy and pegfilgrastim on the same day between January 2003 and December 2007. Any initial diagnosis of t-MDS was clinically confirmed. RESULTS: A total of 227 patients received myelosuppressive chemotherapy and pegfilgrastim on the same day. Median time to follow-up was 3.47 years (IQR 1.15). Two patients had a confirmed diagnosis of t-MDS. The incidence of t-MDS in patients receiving concurrent myelosuppressive chemotherapy and pegfilgrastim in our study population is 0.88%. CONCLUSION: Administering pegfilgrastim at least 1 day after myelosuppressive chemotherapy may help reduce the risk of t-MDS, but more studies with longer follow-up are needed to confirm this finding.
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Antineoplásicos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Quimioterapia Combinada , Feminino , Filgrastim , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/induzido quimicamente , Polietilenoglicóis , Proteínas Recombinantes/administração & dosagem , Estudos RetrospectivosRESUMO
PURPOSE: The postsurgical use of N-acetylcysteine, octreotide, and other agents to reduce mucus accumulation after urinary diversion procedures is described. SUMMARY: Patients undergoing continence-sparing bladder resection are at risk for infection and stone formation due to mucus accumulation. In addition to N-acetylcysteine, agents studied for mucoregulatory control in such patients include aspirin, urea, ranitidine, and octreotide. N-acetylcysteine has high mucolytic activity in vitro, and positive outcomes with instillations of 20% N-acetylcysteine solution have been reported in some patients. Significant mucus reductions were reported in small numbers of patients treated with oral ranitidine 300 mg daily or instillations of 30 mL of urea 40% solution, while the benefits of aspirin are more questionable. To date, there has been only one randomized controlled trial comparing various agents for mucus reduction after reconstructive bladder surgery; the results indicated no significant benefits with the use of N-acetylcysteine, aspirin, or ranitidine. In one small study (n = 40), the use of subcutaneous octreotide immediately before and for 15 days after surgery was reported to yield significant reductions in mucus production, the need for bladder irrigation to clear blockages, and the mean duration of hospital stays. CONCLUSION: Various agents evaluated for mucus control after urinary diversion procedures (oral ranitidine or aspirin, N-acetylcysteine or urea instillations, and subcutaneous octreotide), while reportedly effective for some patients, remain of questionable benefit. More research is needed to define the optimal role of these agents for this indication.