Administration Of Etoposide Research Articles

Systematic therapy for metastatic solid pseudopapillary neoplasm of the pancreas: A single-center experience.

e16341 Background: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor with low-grade malignancy. However, a small proportion of cases still exhibit more aggressive behavior and emerge as distant metastases. Limited data exist on systemic therapy for these entities. Methods: A retrospective analysis was performed on patients diagnosed with SPN of the pancreas who underwent medical treatment in our hospital between January 2020 and December 2023. The clinicopathological characteristics and therapeutic regimens of the patients were collected. The primary outcomes were disease control rate (DCR) and progression free survival (PFS). SPSS software V27.0 was used for data analysis. Results: Five patients were identified and 60.0% of patients were female . The median age was 34 years (range 16-53). All patients first underwent surgical resection. Four individuals had metachronous distant metastasis and one had synchronous distant metastasis. The most common metastatic site was peritoneum (3/5) and liver (3/5), followed by the distant lymph node (2/5). Progesterone receptor positive expression was found in four cases. Four patients received targeted therapy as first-line treatment (3 receiving anlotinib 12mg once daily on days 1-14 every 3 weeks and 1 receiving everolimus 10mg per day). All patients receiving targeted therapy had stable disease, with a DCR of 100%. The median PFS in the targeted therapy group was 8.1 months (95% CI, 6.7-9.5). Only one patient underwent first-line chemotherapy (gemcitabine plus S-1) and experienced disease progression at the initial efficacy evaluation. Data for second-line treatment was available for three patients. One patient got progressive disease (PD) after etoposide administration. Two individuals received everolimus 10mg daily, one of whom showed PD and the other achieved a partial response (PR). All treatment-related adverse events (AEs) were manageable. Conclusions: Metastatic SPN of the pancreas may be not chemosensitive. Targeted therapy, such as anlotinib and everolimus, appears to be a potential therapeutic option.

Sequential haplo-identical conditioning transplant regimen for pediatric patients with relapsed or refractory hemophagocytic lymphohistiocytosis.

Allogeneic hematopoietic stem cell transplantation (HSCT) currently stands as the sole remedy for individuals afflicted with hemophagocytic lymphohistiocytosis (HLH). In this study, we retrospectively evaluated how pediatric patients with relapsed or refractory (R/R) HLH responded to our institution's cocktail conditioning regimen. The disease was diagnosed according to criteria applicable to patients with familial/genetic, relapsing, or severe/persistent HLH. All donors were HLA haplo-identical family donors. In our cohort, sixty-five patients (P-HLH), including 28 with familial/genetic HLH, 36 with secondary HLH, and 1 with an unknown cause, underwent haplo-identical family donor HSCT. The conditioning regimen consisted of intravenous administration of etoposide (VP-16), busulfan, fludarabine, rabbit anti-human thymocyte globulin (r-ATG), and cyclophosphamide (Cy). Tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GvHD) prevention. We observed that the median time for neutrophil recovery was 11 days (range, 8-24), and for platelet counts to exceed 20 × 109/L, it was 14 days (range, 7-130). There were 5 patients (7.7%) who experienced grades III to IV acute GvHD, and 6 patients (9.2%) developed extensive chronic GvHD. The estimated 3- and 5-year overall survival rates were 78.1% (95% CI, 65.8-84.6%) and 74.9% (95% CI, 61.2-84.4%), respectively. The estimated 3- and 5-year event-free survival rates were 73.5% (95% CI, 60.8-82.6%) and 70.3% (95% CI, 56.4-80.5%), respectively. Our findings demonstrate that our innovative conditioning regimen is both effective and safe, offering valuable insights for healthcare professionals evaluating the merits of existing therapies.

Ameliorative potential role of Rosmarinus officinalis extract on toxicity induced by etoposide in male albino rats.

The present work was showed to assess the effect of administration of rosemary extract on etoposide-induced toxicity, injury and proliferation in male rats were investigated. Forty male albino rats were arranged into four equal groups. 1st group, control; 2nd group, etoposide; 3rd group, co-treated rosemary & etoposide; 4th group, rosemary alone. In comparison to the control group, etoposide administration resulted in a significant increase in serum ALT, AST, ALP, total bilirubin, total protein, and gamma GT. In contrast; a significant decrease in albumin level in etoposide group as compared to G1. G3 revealed a significant decrease in AST, ALT, ALP, total protein and total bilirubin levels and a significant rise in albumin level when compared with G2. Serum levels of urea, creatinine, potassium ions, and chloride ions significantly increased; while sodium ions were significantly decreased in G2 when compared with G1. Also, there was an increase of MDA level for etoposide treated group with corresponding control rats. However, there was a remarkable significant decrease in SOD, GPX and CAT levels in G2 as compared to G1. There was a significant increase in serum hydrogen peroxide (H2O2) and Nitric oxide (NO) levels in group treated with etoposide when compared to control group. It was noticeable that administrated by rosemary alone either with etoposide had not any effect on the levels of H2O2 and Nitric oxide. Serum level of T3 and T4 was significantly increased in etoposide-administered rats in comparison with G1. The administration of rosemary, either alone or with etoposide, increased the serum levels of T3 and T4 significantly when compared to control rats. The gene expression analysis showed significant downregulation of hepatic SOD and GPx in (G2) when compared with (G1). The treatment with rosemary extract produced significant upregulation of the antioxidant enzymes mRNA SOD and GPx. MDA gene was increased in (G2) when contrasted with (G1). Treatment of the etoposide- induced rats with rosemary extract delivered significant decrease in MDA gene expression when compared with etoposide group. Rats treated with etoposide showed significant decline in hepatic Nrf2 protein expression, when compared with G1. While, supplementation of Etoposide- administered rats with the rosemary produced a significant elevation in hepatic Nrf2 protein levels. Additionally, the liver histological structure displayed noticeable degeneration and cellular infiltration in liver cells. It is possible to infer that rosemary has a potential role and that it should be researched as a natural component for etoposide-induced toxicity protection.

Etoposide Therapy of Cytokine Storm Syndromes.

Etoposide has revolutionized the treatment of primary as well as secondary hemophagocytic lymphohistiocytosis (HLH), and it is, together with corticosteroids, the most widely used therapy for HLH. In the early 1980s, long-term survival in primary HLH was <5% but with the etoposide-/dexamethasone-based protocols HLH-94 and HLH-2004, in combination with stem cell transplantation, 5-year survival increased dramatically to around 60%in primary HLH, and based on analyses from the HLH-2004 study, there is likely room for further improvement. Biologically, etoposide administration results in potent selective deletion of activated T cells as well as efficient suppression of inflammatory cytokine production. Moreover, etoposide has also been reported to promote programmed cell death (apoptosis) rather than proinflammatory lytic cell death (pyroptosis), conceivably ameliorating subsequent systemic inflammation, i.e., a treatment very suitable for cytokine storm syndromes (CSS). The combination of etoposide and corticosteroids may also be beneficial in cases of severe or refractory secondary HLH (sHLH) with imminent organ failure, such as infection-associated HLH caused by Epstein-Barr virus (EBV) or malignancy-triggered HLH. In CSS associated with rheumatic diseases (macrophage activation syndrome, MAS or MAS-HLH), etoposide is currently used as second- or third-line therapy. Recent studies suggest that etoposide perhaps should be part of an aggressive therapeutic intervention for patients with severe refractory or relapsing MAS, in particular if there is CNS involvement. Importantly, awareness of sHLH must be further increased since treatment of sHLH is often delayed, thereby missing the window of opportunity for a timely, effective, and potentially life-saving HLH-directed treatment.

Whey preparation as an adjuvant to minimise the Intestinal inflammatory status in mucositis rat model

To study the effect of Whey Preparation on intestinal mucositis, model developed by administration of single dose of etoposide (60mg/Kg body wt., i.p). The experimental procedure included Adult albino rats (10±1 week old) of Wistar strain (n=30, 6/group). Freshly prepared whey preparation-(100 and 200mg/Kg/body wt.) was administered by orogastric gavage- Pre, both pre and post etoposide injection. Effectiveness of whey preparation was determined by estimating the biochemical parameters including intestinal Tumor Necrosis Factor-α, Interleukin-6, sodium potassium ATPase, inflammatory markers- Cyclooxygenase and Myeloperoxidase along with Nitric Oxide and reduced Glutathione with and without intervention after 72 hrs. of etoposide injection. There was a significant increase in the Tumor Necrosis Factor –α, Interleukin-6 levels and extent of apoptosis in etoposide controls. Etoposide administration caused a significant decreased the activity of Na+-K+ ATPase and reduced glutathione levels in intestinal tissue. However, in the post treatment groups, Tumor Necrosis Factor–α, Interleukin-6 as well as extent of apoptosis were reverted to normal after whey preparation administration.Whey Preparation gavage in both the study groups- pre and both pre and post etoposide exposure showed that intervention was able to preserve/ prevent changes in the biochemical activity. The results support the WP potentials to reduce the deleterious effects of etoposide on normal cells, which leads to mucositis.

Clinical Features and Outcomes of Hemophagocytic Lymphohistiocytosis Secondary to Lymphoma: Insights from a Tertiary Center in Saudi Arabia

Introduction: Lymphoma encompasses a prominent cause of secondary hemophagocytic lymphohistiocytosis (HLH), an aggressive hyperinflammatory syndrome characterized by immune dysregulation. The concurrence of lymphoma and HLH represents a challenging entity due to the ambiguity of clinical features and paucity of standardized treatment regimens. Limited data exists regarding the characteristics and outcomes of secondary HLH within the Middle East and Saudi Arabia. Moreover, the structure of the population within our region, characterized by a predominance of males and young adults, offers a unique perspective to the literature regarding secondary HLH. Herein, we evaluate the clinical features and outcomes of patients presenting with HLH secondary to lymphoma at a tertiary center in Saudi Arabia. Methods: We retrospectively reviewed the electronic medical records of patients diagnosed with lymphoma over the past ten years at our center to identify patients who developed secondary HLH. The Kaplan-Meier method was used to estimate median overall survival (OS). OS was defined as the incidence of death from any cause from the onset of HLH diagnosis until the end of follow-up. The Cox proportional hazards model was used to identify demographic, clinical, and treatment associated prognostic indicators which had a significant impact on OS. Results: A total of 1484 patients with lymphoma were identified, of which seventeen (1.1%) patients had concurrent HLH. Of the seventeen patients, the median age was 42 years (range 17-64) with 5 (29.4%) patients aged 50 and over. Interestingly, all 17 (100.0%) patients within our cohort were male. Regarding lymphoma subtypes, 10 (58.8%) patients had T and NK-cell lymphoma, 5 (29.4%) had B -cell lymphoma, and 2 (11.7%) had Hodgkin lymphoma. The median HScore was 272.0 (range 182-337) whereas the median HLH-2004 diagnostic criteria score was 6 out of 8 points (range 4-8). Hemophagocytic features in the bone marrow were present in 13 (76.5%) patients. Epstein-Barr virus infection was detected in 9 (52.9%) patients with a median quantitative PCR level of 37347.5 IU/mL (range 1960.0-402847.0). HLH therapy utilized in our patient sample included corticosteroids in 15 (88.2%) patients, etoposide in 8 (47.1%) patients, and intravenous immunoglobulin in 3 (17.6%) patients. Death occurred in 7 (41.2%) patients whilst the median OS of the cohort was 13.0 months (95% CI 0.0-27.4). Using the cox proportional hazards model, both age ≤50 years (P=0.04, hazard ratio=0.186) and etoposide administration (P=0.002, hazard ratio=0.011) were associated with significantly improved survival. Conclusions: To our knowledge, this is the first cohort study reporting the clinical features and outcomes of HLH secondary to lymphoma within our region. Our study highlights the significant disparities between our population and other countries across the globe as our cohort demonstrated a significant male predominance as well as a relatively young median age at diagnosis. Nonetheless, the survival outcomes of secondary HLH remain poor despite the advances in the diagnostication and recognition of the disease. Future efforts ought to explore both the pathophysiological mechanisms underlying lymphoma-associated HLH and the efficacy of different targeted therapeutic modalities.

A pharmacovigilance study of etoposide in the FDA adverse event reporting system (FAERS) database, what does the real world say?

Introduction: Etoposide is a broad-spectrum antitumor drug that has been extensively studied in clinical trials. However, limited information is available regarding its real-world adverse reactions. Therefore, this study aimed to assess and evaluate etoposide-related adverse events in a real-world setting by using data mining method on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.Methods: Through the analysis of 16,134,686 reports in the FAERS database, a total of 9,892 reports of etoposide-related adverse drug events (ADEs) were identified. To determine the significance of these ADEs, various disproportionality analysis algorithms were applied, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms.Results: As a result, 478 significant disproportionality preferred terms (PTs) that were identified by all four algorithms were retained. These PTs included commonly reported adverse events such as thrombocytopenia, leukopenia, anemia, stomatitis, and pneumonitis, which align with those documented in the drug’s instructions and previous clinical trials. However, our analysis also uncovered unexpected and significant ADEs, including thrombotic microangiopathy, ototoxicity, second primary malignancy, nephropathy toxic, and ovarian failure. Furthermore, we examined the time-to-onset (TTO) of these ADEs using the Weibull distribution test and found that the median TTO for etoposide-associated ADEs was 10 days (interquartile range [IQR] 2–32 days). The majority of cases occurred within the first month (73.8%) after etoposide administration. Additionally, our analysis revealed specific high-risk signals for males, such as pneumonia and cardiac infarction, while females showed signals for drug resistance and ototoxicity.Discussion: These findings provide valuable insight into the occurrence of ADEs following etoposide initiation, which can potentially support clinical monitoring and risk identification efforts.

Cytotoxic Effect of L-Methioninase from Brevibacterium linens BL2 in Combination with Etoposide against Glioblastoma Cells

L-methioninase degrades methionine, which is essential in methionine-dependent cancer cells, resulting in specific cell death. Normal cells can synthesize their own methionine amino acids even in the absence of exogenous methionine. This selective targeting of cancer cells makes L-methioninase a promising therapeutic candidate for cancer. In this study, L-methioninase was partially purified from Brevibacterium linens BL2. The specific activity of the enzyme was found as 3.055 units/mg. IC50 values (24 h) of the enzyme were 5.792 units/mL for U87MG cell line and 5.215 units/mL for T98G cell line. When L-methioninase and etoposide were used in combination, synergistic cytotoxic and cell migration inhibition effects on U87MG and T98G cells alongside decreased cytotoxic activity on the Mouse Embryonic Fibroblast and HaCaT cells compared to etoposide alone were observed. Additionally, colony numbers of U87MG cells were significantly reduced by L-methioninase and etoposide administration after 21 days of incubation. Furthermore, L-methioninase suppressed the expression levels of survivin and c-Myc while increasing the expression level of Caspase-3 in both glioblastoma cell lines. These effects were enhanced when etoposide was used in combination with etoposide. This investigation reveals that the L-methioninase enzyme not only exhibited cytotoxic effects on U87MG and T98G cells but also enhanced the anti-proliferative effects of etoposide when used in combination while also demonstrating fewer adverse effects on normal cells.

"Sandwich" protocol based on modified SMILE regimen for children with newly extranodal NK/T cell lymphoma, nasal type: a single-arm, single-center clinical study.

Extranodal NK/T-cell lymphoma, nasal type (ENKTL), which is a rare form of mature T/NK cell lymphoma in children, currently lacks a standardized first-line treatment approach. However, a treatment protocol known as the "sandwich" regimen has been used in children newly diagnosed with ENKTL. This protocol combines the administration of methotrexate, ifosfamide, etoposide, pegaspargase, and dexamethasone (referred to as SMILE) with the addition of radiotherapy (RT). From September 2017 to December 2020, a total of five patients were included in the study, consisting of three males and two females. The median age of onset was 10.6 years (range, 9.8 to 14.0 years). Among the patients, four had nasal/nasopharyngeal disease at stage II, while one patient had extra nasal disease involving the skin at stage IV. The median EBV-DNA level in plasma was 1.68 × 103 copies/ml (range, 0.44 to 21.1 × 103copies/ml). All the patients had good overall response after 2 cycles of chemotherapy and radiotherapy, including 4 of the patients who had a complete response and 1 of the patients with partial remission. The patient with stage IV received allogeneic hematopoietic stem cell transplantation after the EBV-DNA level was elevated again during treatment. One patient in the low-risk group experienced grade 4 oral mucositis, while no other severe complications or treatment-related deaths were observed. The median follow-up period was 22 months (range, 5 to 57 months). All five patients successfully completed their treatment, with four patients achieving event-free survival, and one patient was lost to follow-up. The median OS time and EFS time was 33 months (range: 18-57 months) and 20 months (range: 5-47 months), respectively. The sandwich protocol has demonstrated a high response rate, good tolerance to chemotherapy, and no treatment-related fatalities. However, further confirmation is necessary through additional clinical studies involving larger sample sizes. Clinical trial registration number: Due to modified SMILE regimens with sandwiched radiotherapy yielded promising outcomes in children ENKTL, we have carried out a phase II multicenter clinical trial (ChiCTR220005954) for children ENKTL in China to further verify the efficacy and safety.

Risk factors for obesity in adulthood among survivors of childhood cancer

AbstractObjectiveThe aim of this study was to identify risk factors for obesity in childhood cancer survivors (CCSs).MethodsThe study included 3199 patients of the French Childhood Cancer Survivor Study cohort, with 303 patients with obesity who had returned the self‐questionnaire. Analyses were adjusted for social deprivation index and sex.ResultsCCSs were less likely to have obesity (9.5%; 95% CI: 8.5%–10.5%) than expected from the general French population rates (12.5%; p = 0.0001). Nevertheless, brain tumor survivors were significantly more likely to develop obesity than the general French population (p = 0.0001). Compared with patients who did not receive radiotherapy to the pituitary gland, those who received a dose &gt;5 Gy had an increased risk of obesity: relative risk 1.9 (95% CI: 1.2–3.1), 2.5 (95% CI: 1.7–3.7), and 2.6 (95% CI: 1.6–4.3), respectively, for participants with 6 to 20 Gy, 20 to 40 Gy, and ≥40 Gy of radiation. Etoposide administration significantly increased the risk of obesity (relative risk 1.7; 95% CI: 1.1–2.6). High social deprivation index was also a risk factor, just like BMI at diagnosis.ConclusionsLong‐term follow‐up of CCSs should include weight follow‐up during adulthood.

Evaluating the efficacy and safety of single-agent etoposide intra-CSF chemotherapy in children and young people with relapsed/refractory central nervous system tumours

PurposeThe aim of the project was to evaluate intra-CSF etoposide administration in a palliative setting for children and young people with relapsed/refractory central nervous system (CNS) tumours, with the primary endpoints being overall survival and progression-free survival time. A safety endpoint was to assess the side effect profile and complications of intra-CSF etoposide.MethodsThirty-five patients under the age of 30 years (median age: 5.33 years) were enrolled onto the project. The cross-centre study was a service evaluation, with a data collection spreadsheet designed in Nottingham and completed by both Nottingham and Oxford centres. Data was analysed using SPSS, assessing the overall survival and progression-free survival times, as well as the 6-month and 1-year survival rates.ResultsThe median overall survival and progression-free survival times were 10.97 and 5.91 months, respectively. The 6-month and 1-year overall survival rates were 67% and 48%, and the progression-free survival rates were 50% and 22%. Age at the start of intra-CSF therapy was significantly associated with overall survival (P = 0.046), with the 6 + age group having improved overall survival. Treatment type was significantly associated with overall survival (P = 0.012), with etoposide intra-CSF treatment being associated with improved overall survival. Treatment duration was significantly associated with both overall survival (P < 0.001) and progression-free survival (P < 0.001).ConclusionIntra-CSF etoposide treatment has shown to increase both overall and progression-free survival significantly, whilst having few side effects and maintaining a good quality of life for patients, reflecting it as a beneficial therapy in the palliative setting.

Etoposide hypersensitivity reactions associated with in-line filter use: A retrospective cohort study at CHU de Québec-Université Laval.

A case series of hypersensitivity reactions (HSRs) during intravenous administration of etoposide was observed following the introduction of in-line filters (ILFs) at a specialized university-affiliated center. This raised questions about the possible involvement of filters in these reactions. Despite there being very little published evidence to inform clinical decision making in this potentially clinically significant situation, the use of ILFs was discontinued at this center pending further investigation. The aims of this study were to evaluate the cumulative incidence of etoposide-related HSR with and without the use of ILF and to describe the reactions in adult and pediatric patients with cancer. A retrospective cohort study was performed among all pediatric and adult patients treated with intravenous etoposide at a maximal concentration of 0.4 mg/mL at our center between 30 September 2015 and 16 August 2018. This covered periods of time during which ILFs were used, as well as 6 months before their implementation and after their withdrawal. Data were extracted from medical records and cumulative incidence was calculated for each of the time periods (pre-ILF, ILF, and post-ILF) as the proportion of patients who recorded an HSR (one or more). Confidence intervals were calculated for each proportion using Fisher's Exact 95%. Comparisons of proportions between time periods were performed using Exact Pearson Chi-squared tests. Data were stratified by a number of perfusion cycles (single cycle or multiple cycles) and by patient population (adult and pediatric). A total of 284 patients were included in the study. The overall cumulative incidence of etoposide HSR was 9.9%. The cumulative incidence of HSR tended to be higher during ILF use when compared with combined pre- and post-ILF periods (12.2% [95% CI: 7.9-17.8] vs. 5.2% [95% CI: 1.7-11.7], p = 0.09). In patients who received multiple cycles of etoposide, the cumulative incidence of HSRs was higher during ILF use when compared with combined pre- and post-ILF periods (15.0% [95% CI: 9.6-21.8] vs. 3.9% [95% CI: 0.8-11.0], p = 0.01). The majority of HSRs' maximal severity were grade 1 or 2 (85.7%) according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. This study suggests a link between the use of ILFs and increased incidence of HSR during etoposide perfusion.

Etoposide treatment in secondary hemophagocytic syndrome: impact on healthcare-associated infections and survival

BackgroundEtoposide remains the cornerstone of symptomatic management of critically ill patients with secondary hemophagocytic syndrome (sHS). Risk of healthcare-associated infections (HAIs) in this setting with etoposide has never been assessed. We sought to evaluate the association between etoposide administration, HAIs occurrence and survival in critically ill adult patients with sHS. In this retrospective single-center study conducted in a university hospital ICU between January 2007 and March 2020, all consecutive patients with sHS were included. HAIs were defined as any microbiologically documented infection throughout ICU stay. Competing risk survival analysis was performed to determine factors associated with HAIs. Propensity score-based overlap weighting was performed to adjust for factors associated with etoposide use.Results168 patients with a median age of 49 [38, 59] were included. Forty-three (25.6%) patients presented with at least 1 microbiologically documented HAI throughout ICU stay. After adjustment, cumulative incidence of HAI was higher in patients receiving etoposide (p = 0.007), while survival was unaffected by etoposide status (p = 0.824). By multivariable analysis, etoposide treatment was associated with a higher incidence of HAIs (sHR 3.75 [1.05, 6.67]), whereas no association with survival (sHR 0.53 [0.20, 1.98]) was found. Other factors associated with increased mortality after adjustment included age, immunodepression, male sex, SOFA score > 13, and occurrence of HAI.ConclusionsIn patients with sHS, etoposide treatment is independently associated with increased occurrence of HAIs, whereas no association with survival was found. Intensivists should be aware of increased infectious risk, to promptly detect and treat infections in this specific setting. Studies to assess benefits from prophylactic anti-infectious agents in this setting are warranted and the lack of benefit of etoposide on survival needs to be interpreted cautiously.

Effectiveness of oral etoposide in recurrent or refractory epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer

The aim of treatment in recurrent or refractory epithelial ovarian cancer is palliation. In a patient with platinum-resistant status, several chemotherapy regimens have been reported with similar response rates. Among these agents, the oral etoposide holds an advantage of the route of administration and management in the out-patient setting. This retrospective study was conducted to evaluate the effectiveness of oral etoposide. Data of patients with recurrent or refractory epithelial ovarian, primary peritoneal and fallopian tube cancer who received oral etoposide treatment in Ramathibodi Hospital, Mahidol University from January 1997 to December 2017 were collected. Progression-free survival (PFS) and overall survival (OS) were primary and secondary outcomes, respectively. The oral etoposide at a dose of 50 mg/m2 was prescribed. Sixty-six records were analysed. Median OS and median PFS were 8.3 months (95% confidence interval (CI): 6.8, 10.4) and 3.1 months (95%CI: 2.3, 3.9), respectively. Other factors including age, body mass index (BMI), histopathology subtype, primary treatment, result of the primary surgery, platinum status, site and size of recurrent cancer, treatment after discontinuation of oral etoposide and the line of chemotherapy regimen were not associated with the prognosis. The initial cancer stage was the only independent poor prognostic factor. The main toxicity was neutropenia. Impact Statement What is already known on this subject? After the recurrence of epithelial ovarian cancer, peritoneal cancer or fallopian tube cancer, the aim of treatment in this setting is palliation with accentuating on symptomatic control and enhancing the quality of life. According to previous clinical trials, the chemotherapy regimens which were considered as a second-line or beyond the second-line therapy have been reported with similar response rates. Among these agents, the oral etoposide could be administrated by oral route. There were several articles reported the effectiveness of oral etoposide in different dosage. What do the results of this study add? This study adds that administration of oral etoposide at a dose of 50 mg/m2 showed fairish oncologic outcomes with manageable toxicity. What are the implications of these findings for clinical practice and/ or further research? The results will provide evidence that the oral etoposide can be considerate as a choice of palliative chemotherapy because of an advantage of the route of administration and management in the out-patient setting.

Feasibility and safety of outpatient administration of ifosfamide and etoposide for pediatric patients with Ewing sarcoma in a resource-limited setting amid the COVID-19 pandemic.

BackgroundTo assess feasibility and safety of outpatient administration of ifosfamide and etoposide (IE) for pediatric Ewing sarcoma (EWS) patients in a resource‐limited setting amid the COVID‐19 pandemic.Materials and MethodsRetrospective study of patients with EWS who received outpatient IE from January 2020 until January 2021 at our institution. Ifosfamide 1800 mg/m2 was given for 5 days with MESNA (2‐mercaptoethane sulfonate sodium) infusion and additional boluses before and after 9 hours of hydration. Patients >10 years of age with the ability to drink orally at home, no pre‐existing renal dysfunction or history of hematuria were included. They were monitored for hemorrhagic cystitis with a urine dipstick before, midway, and at end of infusion. A urine analysis was done 24 hours after the last dose of ifosfamide.ResultsForty‐seven (100%) cycles were given as outpatient during the study period. Thirty‐five (74%) cycles were given on time, two (4%) cycles were delayed due to mucositis, two (4%) due to delayed count recovery, and eight (18%) due to unavailability of outpatient appointments. The median interval between these cycles was 15 days (range 14–44 days). No episode of hemorrhagic cystitis was reported. Urine analysis was not done at 24 hours for 27 (58%) cycles, so microscopic hematuria may have been missed. This outpatient protocol saved 32% (USD 299) per cycle in cost and 282 days of hospitalization.ConclusionOutpatient administration of IE for pediatric patients with EWS is feasible, safe, and cost‐effective during the COVID‐19 pandemic.

Successful Neoadjuvant Chemotherapy for Small-Cell Neuroendocrine Carcinoma of the Pancreas: A Case Report.

Neoadjuvant therapy for pancreatic neuroendocrine tumors may potentially aid downstaging, increase the possibility of radical surgery. We herein report a case of a 63-year-old man who had been diagnosed with locally advanced small-cell neuroendocrine carcinomas of the pancreas according to the diagnostic biopsy. The patient received 6 courses of etoposide and cisplatin as neoadjuvant therapy in an attempt to stop tumor progression, which promoted obvious tumor shrinkage without adverse effects and allowed subsequent Appleby procedure, the distal pancreatectomy with celiac artery resection. The patient showed no recurrence in the follow-up of a contrast-enhanced computed tomographic scan, which is 8 months after surgery. To the best of our knowledge, this is a rare case to report etoposide and cisplatin administration before surgery for unresectable pancreatic neuroendocrine carcinoma promoted a pathological partial response and finally achieved a radical surgery, providing a novel therapeutic option for patients with locally advanced pancreatic neuroendocrine carcinoma.

Therapeutic administration of etoposide coincides with reduced systemic HMGB1 levels in macrophage activation syndrome

BackgroundMacrophage activation syndrome (MAS) is a potentially fatal complication of systemic inflammation. HMGB1 is a nuclear protein released extracellularly during proinflammatory lytic cell death or secreted by activated macrophages, NK cells, and additional cell types during infection or sterile injury. Extracellular HMGB1 orchestrates central events in inflammation as a prototype alarmin. TLR4 and the receptor for advanced glycation end products operate as key HMGB1 receptors to mediate inflammation.MethodsStandard ELISA and cytometric bead array-based methods were used to examine the kinetic pattern for systemic release of HMGB1, ferritin, IL-18, IFN-γ, and MCP-1 before and during treatment of four children with critical MAS. Three of the patients with severe underlying systemic rheumatic diseases were treated with biologics including tocilizumab or anakinra when MAS developed. All patients required intensive care therapy due to life-threatening illness. Add-on etoposide therapy was administered due to insufficient clinical response with standard treatment. Etoposide promotes apoptotic rather than proinflammatory lytic cell death, conceivably ameliorating subsequent systemic inflammation.ResultsThis therapeutic intervention brought disease control coinciding with a decline of the increased systemic HMGB1, IFN-γ, IL-18, and ferritin levels whereas MCP-1 levels evolved independently.ConclusionSystemic HMGB1 levels in MAS have not been reported before. Our results suggest that the molecule is not merely a biomarker of inflammation, but most likely also contributes to the pathogenesis of MAS. These observations encourage further studies of HMGB1 antagonists. They also advocate therapeutic etoposide administration in severe MAS and provide a possible biological explanation for its mode of action.

Therapy-related acute myeloid leukemia with KMT2A-SNX9 gene fusion associated with a hyperdiploid karyotype after hemophagocytic lymphohistiocytosis

Therapy-related acute myeloid leukemia (t-AML) following treatment with topoisomerase-II inhibitors has been increasingly reported. These compounds (e.g. etoposide) promote DNA damage and are associated with KMT2A rearrangements. They are widely used as first-line treatment in hemophagocytic lymphohistiocytosis (HLH). Here we describe a newborn who developed t-AML after HLH treatment. We provide detailed clinical, cytogenetic, and molecular characteristics of this patient, including the identification of a novel gene fusion – KMT2A-SNX9 – in t-AML. Considering the dismal outcome of this case, we discuss the side-effects of etoposide administration during HLH treatment in infants.

Four Cycles of Etoposide plus Cisplatin for Patients with Good-Risk Advanced Germ Cell Tumors

BackgroundThe National Comprehensive Cancer Network recommends either three cycles of bleomycin, etoposide, and cisplatin or four cycles of etoposide and cisplatin (EPx4) as initial chemotherapy for the treatment of good‐risk germ cell tumors (GCTs). To assess the response, toxicity, and survival outcomes of EPx4, we analyzed our experience.Material and MethodsResponse and survival outcomes, selected toxicities, and adherence to chemotherapy dose and schedule were assessed in patients with good‐risk GCT who received EPx4 at Memorial Sloan Kettering Cancer Center between 1982 and 2016. The results were compared with our past results and published data.ResultsBetween 1982 and 2016, 944 patients with GCT were treated with EPx4, 289 who were previously reported plus 655 treated between January 2000 and August 2016. A favorable response was achieved in 928 of 944 patients (98.3%). Five‐year progression‐free, disease‐specific, and overall survival rates were 93.9%, 98.6%, and 97.9%, respectively. Median follow‐up was 7.3 years (range, 2.8 months to 35.5 years). Viable, nonteratomatous malignant GCT was present in 3.5% of 432 postchemotherapy retroperitoneal lymph node dissection specimens from patients with nonseminomatous GCT. Febrile neutropenia and thromboembolic events occurred in 16.0% and 8.9%, respectively, with one treatment‐related death. In the more recent 655‐patient cohort, full‐dose EPx4 was administered to 631 (96.3%), with deviations from planned treatment driven mainly by vascular (n = 13), hematologic (n = 11), renal (n = 7), or infectious (n = 5) events.ConclusionEPx4 is highly effective and well tolerated in patients with good‐risk GCTs and remains a standard of care.Implications for PracticeFour cycles of etoposide and cisplatin (EPx4) is a standard‐of‐care regimen for all patients with good‐risk germ cell tumors with a favorable response rate and disease‐specific survival of 98%. Full‐dose administration of etoposide and cisplatin and complete resection of residual disease lead to optimal outcomes. EPx4 should be the recommended regimen in active smokers, patients with reduced or borderline kidney function, and patients aged 50 years or older, which are patient groups at increased risk for bleomycin pulmonary toxicity. Because of a risk of acquired severe pulmonary illness, EPx4 may also be favored for patients who vape or use e‐cigarettes and during ongoing transmission of severe acute respiratory syndrome coronavirus 2.

P50.10 Intravenous (IV) versus IV/oral route of etoposide administration: impact on real-world SCLC survival outcomes

Platinum-etoposide doublet (PE) is the recommended first-line (1L) chemotherapy for small cell lung cancer (SCLC). Evidence shows that oncology patients prefer oral treatment to IV. This study compared outcomes between 1L intravenous (IV), and IV followed by oral (IV/oral) route of etoposide administration in real-world SCLC patients in Alberta, Canada. SCLC patients who were diagnosed between 2010 and 2016 and completed 1L etoposide at an academic tertiary cancer centre, (Tom Baker Cancer Centre) were included. Data were retrieved from the Glans-Look database excluding those with mixed histology. Outcomes explored included, a] overall survival, (OS), the time in months from diagnosis date to death/last contact, b] tumor objective response rate (ORR), the complete and partial responses as defined by the RECIST v1.1 criteria, using diagnostic imaging reports within 4-8 weeks post 1L or as reported in oncologist progress notes, and c] 1L-related toxicity rate, derived from progress notes, graded using the CTCAE criteria (version 5). Also measured was the progression free survival (PFS): time difference in months from diagnosis date to first progression post 1L or death, whichever occurs first. Comparison between IV/oral and IV groups was performed using Fisher’s Exact (point estimates), Log-Rank tests (Kaplan-Meier survival estimates) and Cox proportional hazard model (survival outcome predictors). A priori statistical significance was p < 0.05. Analyses were performed using SPSS statistical software (version 25). There were 222 patients, 1L was mostly PE [93%] employing etoposide in combination with cisplatin [61%] or carboplatin [32%]. 168 [76%] were IV/oral group. Median age was 66 years, 132 [60%] female, and 138 [62%] had extensive stage SCLC (ES). Performance status (ECOG) was 0-2 in 112 (51%), ≥3 in 9 (4%) and unknown in 101 (46%) patients. IV and IV/oral patients have similar characteristics, but compared to IV/oral, the IV group had less limited stage disease (LS), [p=0.28]. 100 patients experienced grade 3 or 4 toxicities, mainly neutropenia [83%]. The rates were similar for IV/oral versus IV group, p= 0.36. Stratified by stage however, toxicity from IV was greater in LS than ES patients [60 vs 39%]. Overall, ORR for IV/oral versus IV group was 71% vs 66%, [p=0.85]. Within stage, ORR was 79 vs. 89% in LS [p< 0.01] and 58 vs 71% in ES [p=0.23], IV/oral relative to IV group. There was no statistically significant difference in PFS or OS with IV/oral relative to IV groups [PFS: 14 vs 12 months for LS; both 6 months for ES; OS: 32 vs 25 mo. for LS; 12 vs 14 mo. for ES]. Predictors of favorable survival include presence of grade 3 or 4 toxicity in LS [HR= 0.45, p=0.03] and second-line chemotherapy receipt in ES [HR= 0.46, p<0.01]. Consistent with previous reports, we found high oral treatment rate in real-world SCLC patients and no statistically significant differences in SCLC survival outcomes comparing IV/oral versus IV group. Future studies may explore why severe chemotherapy-related toxicity (grade 3 or 4) in LS patients predicts favorable survival.