Intravitreal melphalan therapy for vitreous seeds in retinoblastoma: Implementation and outcomes of a new chemotherapy protocol

2020 ◽  
Vol 26 (8) ◽  
pp. 1829-1835 ◽  
Author(s):  
Antonio Solana-Altabella ◽  
Silvia Valero ◽  
Julia Balaguer ◽  
Paloma Escobar-Cava ◽  
Honorio Barranco ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Effects ◽  
Health Outcomes ◽  
Chemotherapeutic Agent ◽  
Treatment Protocol ◽  
Treatment Team ◽  
Intravitreal Chemotherapy ◽  
Chemotherapy Protocol ◽  
Salt And Pepper ◽  
Vitreous Seeds

Retinoblastoma is the most common paediatric ocular tumour, which appears in the retina. Without treatment, retinoblastoma grows and destroys the internal ocular globe architecture, even leading to metastasis. When treated, overall survival is close to 97%, the alkylating drug melphalan being the most extensively used chemotherapeutic agent in localised treatment. The aim of this study is to describe the implementation of a new intravitreal chemotherapy retinoblastoma treatment protocol for children implanting vitreous seeds through intravitreal melphalan injections and to evaluate the patients’ health outcomes treated with it. Between December 2014 and July 2018, seven patients were treated with this protocol. They received a mean of 3.3 cycles of intravitreal melphalan with standard doses of 30 mcg per cycle. In the seven eyes treated in our hospital, the response was as expected; three eyes with vitreous seedings (43%) were successfully treated. The main adverse effects presented by all patients were scars at cryogenisation points. In two patients, the appearance of ‘salt and pepper’ retinopathy was reported. Oncology pharmacists, as part of the treatment team, can provide information about recommended doses, expected adverse effects, stability of preparations, most appropriate method of processing, packaging, and methods of drug administration, to ensure efficacy and especially safety in the administration of these drugs.

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

2019 ◽  
Vol 18 (14) ◽  
pp. 1936-1951 ◽  
Author(s):  
Raghav Dogra ◽  
Rohit Bhatia ◽  
Ravi Shankar ◽  
Parveen Bansal ◽  
Ravindra K. Rawal
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Phase Iii ◽  
Acute Myeloid

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

scholarly journals Endocrine response and outcome in 14 cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (17 Gy)

2022 ◽  
pp. 1-8
Author(s):  
Maegan L. Watson-Skaggs ◽  
Tracy L. Gieger ◽  
Hiroto Yoshikawa ◽  
Michael W. Nolan
Keyword(s):  
Insulin Resistance ◽  
Overall Survival ◽  
Adverse Effects ◽  
Survival Time ◽  
Stereotactic Radiosurgery ◽  
Insulin Dose ◽  
Exogenous Insulin ◽  
Endocrine Response ◽  
Overall Survival Time ◽  
Insulin Requirements

Abstract OBJECTIVE To describe clinical outcomes in cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (SRS). ANIMALS 14 client-owned cats. PROCEDURES Medical records of cats with insulin resistance and acromegaly treated with SRS (17 Gy) between August 2013 and November 2019 at a single institution were reviewed. Kaplan-Meier analysis was used to evaluate overall survival time. RESULTS Acute adverse effects of SRS included somnolence (n = 2) and alopecia (1). Delayed adverse effects of SRS included unspecified neurologic complications (n = 1; 481 days), seizures (1; 1,541 days), and hypothyroidism (1; 64 days). Exogenous insulin requirements decreased in 10 of the 14 cats, with a median time to lowest insulin dose of 399 days (range, 42 to 879 days). Complete diabetic remission was achieved in 3 cats. The median overall survival time was 741 days (95% CI, 353 to 1,129 days). Six cats were still alive at the end of the study period, with a median follow-up time of 725 days. In 7 of the 8 cats that had died, death was presumptively attributed to acromegaly owing to continued insulin resistance, organ failure, or altered neurologic status. CLINICAL RELEVANCE The SRS protocol was well tolerated and associated with survival times similar to those reported previously. Most cats had decreased exogenous insulin requirements after SRS. Latency to an endocrine response was highly variable, emphasizing the need for careful ongoing diabetic monitoring of acromegalic cats after pituitary gland irradiation.

scholarly journals Artesunate induces mitochondria-mediated apoptosis of human retinoblastoma cells by upregulating Kruppel-like factor 6

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Ying Yang ◽  
Nandan Wu ◽  
Yihui Wu ◽  
Haoting Chen ◽  
Jin Qiu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Apoptosis ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Chemotherapeutic Drug ◽  
Sprague Dawley ◽  
Fundus Fluorescein Angiography ◽  
Intravitreal Chemotherapy ◽  
Vitreous Seeds

Abstract Retinoblastoma (RB) is the most common primary intraocular malignancy in children. Intravitreal chemotherapy achieves favorable clinical outcomes in controlling RB vitreous seeds, which are a common reason for treatment failure. Thus, a novel, effective and safe intravitreal chemotherapeutic drug is urgently required. The malaria drug artesunate (ART) recently demonstrated remarkable anticancer effects with mild side effects. The purpose of this study is to investigate the anti-RB efficacy, the underlying mechanism and the intraocular safety of ART. Herein, we verified that ART inhibits RB cell viability and induces cell apoptosis in a dose- and time-dependent manner. Microarray analysis revealed that Kruppel-like factor 6 (KLF6) was upregulated after ART treatment, and this was further confirmed by real-time PCR and western blot assays. Silencing of KLF6 expression significantly reversed ART-induced RB cell growth inhibition and apoptosis. Furthermore, ART activated mitochondria-mediated apoptosis of RB cells, while silencing KLF6 expression significantly inhibited this effect. In murine xenotransplantation models of RB, we further confirmed that ART inhibits RB tumor growth, induces tumor cell apoptosis and upregulates KLF6 expression. In addition, KLF6 silencing attenuates ART-mediated inhibition of tumor growth in vivo. Furthermore, we proved that intravitreal injection of ART in Sprague-Dawley (SD) rats is safe, with no obvious retinal function damage or structural disorders observed by electrophysiology (ERG), fundal photographs, fundus fluorescein angiography (FFA) or optical coherence tomography (OCT) examinations. Collectively, our study revealed that ART induces mitochondrial apoptosis of RB cells via upregulating KLF6, and our results may extend the application of ART to the clinic as an effective and safe intravitreal chemotherapeutic drug to treat RB, especially RB with vitreous seeds.

scholarly journals Patient-Reported Outcome Results From the Open-Label, Randomized Phase III Myeloma X Trial Evaluating Salvage Autologous Stem-Cell Transplantation in Relapsed Multiple Myeloma

2019 ◽  
Vol 37 (19) ◽  
pp. 1617-1628 ◽  
Author(s):  
Sam H. Ahmedzai ◽  
John A. Snowden ◽  
Andrew John Ashcroft ◽  
David Allan Cairns ◽  
Cathy Williams ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Adverse Effects ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Random Assignment ◽  
Time To Progression ◽  
Patient Reported

PURPOSE Salvage autologous stem-cell transplantation (sASCT) in patients with multiple myeloma (MM) relapsing after a prior autologous stem-cell transplantation leads to increased remission duration and overall survival. We report a comprehensive study on patient-reported outcomes, including quality of life (QoL) and pain in sASCT. METHODS Patients were randomly assigned to either sASCT or nontransplantation consolidation (NTC). Pain and QoL were assessed as secondary outcomes using validated QoL instruments (European Organisation for Research and Treatment of Cancer QLQ-C30 and myeloma-specific module, QLQ-MY20; the Brief Pain Inventory [Short Form]; and the Leeds Assessment of Neuropathic Symptoms and Signs [Self-Assessment] scale). RESULTS A total of 288 patients (> 96%) consented to the QoL substudy. The median follow-up was 52 months. The European Organisation for Research and Treatment of Cancer QLQ-C30 Global health status scores were higher (better) in the NTC group at 100 days after random assignment ( P = .0496), but not at later time points. Pain interference was higher (worse) in the sASCT group than in the NTC group at 6 months after random assignment ( P = .0267), with patients with sASCT reporting higher scores for Pain interference with daily living for up to 2 years after random assignment. Patients reporting lower concerns about adverse effects of treatment after sASCT had a time to progression advantage. CONCLUSION Patients with sASCT with relapsed MM demonstrated a comparative reduction in QoL and greater impact of treatment adverse effects lasting for 6 months and up to 2 years for pain, after which patients who had received sASCT reported better outcomes. Patients who experienced lower adverse effects after sASCT had longer time to progression and overall survival, showing the need to improve symptom management peritransplantation. To our knowledge, this study provides the most comprehensive picture of QoL before and after sASCT in patients with relapsed MM.

scholarly journals Doxorubicin-Based Chemotherapy for the Palliative Treatment of Adult Patients with Locally Advanced or Metastatic Soft-Tissue Sarcoma: A Meta-Analysis and Clinical Practice Guideline

Sarcoma ◽  
2000 ◽  
Vol 4 (3) ◽  
pp. 103-112 ◽  
Author(s):  
Vivien H. C. Bramwell ◽  
Dale Anderson ◽  
Manya L. Charette
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Adverse Effects ◽  
Combination Therapy ◽  
Meta Analysis ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Soft Tissue Sarcoma ◽  
Single Agent Chemotherapy

Purpose.To make recommendations for the use of doxorubicin-based chemotherapy in patients with soft-tissue sarcoma.Patients.The recommendations apply to patients with symptomatic unresectable locally advanced or metastatic soft-tissue sarcoma who are candidates for palliative chemotherapy.Methods.A systematic review of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice to develop an evidence-based practice guideline.Results.Eight randomized trials comparing doxorubicin-based combination versus doxorubicin single-agent chemotherapy were reviewed. Response rates and overall survival were evaluated using pooled statistical analysis.The pooled response data in 2281 patients showed a slight trend favouring the combination therapy, although this did not reach statistical significance (odds ratio (OR), 0.79; 95% confidence interval (CI), 0.60–1.05;p=0.10). Survival data could only be abstracted from six studies involving 2097 patients, and showed no significant advantage for combination therapy (OR, 0.84; 95% CI, 0.67–1.06;p=0.13). Data on adverse effects could not be combined in a meta-analysis; however nausea, vomiting and myelosuppression were consistently more severe with combination chemotherapy than with single-agent chemotherapy.Discussion.Single-agent doxorubicin is an appropriate first-line chemotherapy option for advanced or metastatic soft-tissue sarcoma. Some doxorubicin-based combination chemotherapy regimens, given in conventional doses, produce only marginal increases in response rates, at the expense of increased adverse effects, and with no improvements in overall survival. Future randomized clinical trials should compare new regimens, whose activity has been established in single-arm studies, with single-agent doxorubicin, and include quality of life as an outcome measure.

Economic Evaluation of Thalidomide Combined with Melphalan and Prednisone in Previously Untreated Multiple Myeloma in Scotland

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2395-2395 ◽  
Author(s):  
Baris Deniz ◽  
Thierry Facon ◽  
Ian Singer ◽  
Paul Micallef-Eynaud ◽  
Ian Joseph ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Adverse Event ◽  
Adverse Events ◽  
Health Outcomes ◽  
Progressive Disease ◽  
Life Time ◽  
Sensitivity Analyses ◽  
List Price ◽  
Model Parameters

Abstract INTRODUCTION: Thalidomide (Thalomid®/Thalidomide Pharmion®) combined with melphalan and prednisone (MPT) yields improved progression-free and overall survival compared to MP alone (Facon et. al., Lancet2007; 370:1191). This study was designed to estimate the life-time health and cost consequences of MPT versus MP in Scottish patients with previously untreated multiple myeloma. METHODS: A Markov model was developed to determine cost and health outcomes for a cohort of patients receiving a course of MPT or MP. The disease course was conceptualized by 4 mutually exclusive health states: pre-progression without adverse events, pre-progression with adverse event, progressive disease, and death. Probabilities of moving between these states (i.e. natural progression plus efficacy and safety of the treatments) were derived from a long-term randomized clinical trial, IFM 99-06 (Facon et. al., Lancet2007; 370:1191). Both patient cohorts remained on the assigned treatment for a maximum of twelve 6-week cycles, until progression or treatment-limiting toxicity. Treatment duration and the average daily dose were modelled to match IFM 99-06. During treatment, each cohort was exposed to adverse event risks associated with therapy estimated from IFM 99-06. Health state utilities associated with adverse events and disease states were obtained from the literature. Thalidomide cost was set at UK list price; routine disease-management costs by disease-state (progressive disease and remission state) reflect clinical practice in Scotland. As recommended by the UK treasury, costs and health outcomes were discounted at 3.5% per annum to adjust to present values. Univariate and multivariate sensitivity analyses were performed around key model parameters. RESULTS: The model estimated improvements in health outcomes with MPT with a median time to progression of 25 months vs. 12 months with MP. Estimated median overall survivals were 4.03 years vs. 2.88 years with MP. These results translate to a gain of 0.91 (3.24 vs. 2.32) quality-adjusted life-years (QALYs). MPT is associated with higher overall costs (£25,199 per patient) compared with MP (£8,935), over the modeled life-time, leading to an incremental cost-effectiveness ratio of £17,847 per QALY and £14,803 per life-year gained. Sensitivity analyses showed that results remained consistent through broad changes in model parameters including the addition of thromboembolic prophylaxis. CONCLUSIONS: MPT delivers improvements in progression-free and overall survival in a life-limiting orphan disease compared to MP and economic results fall within a range considered cost-effective in Scotland.

Treatment outcomes of patients with primary central nervous system lymphoma: Single center experience from south India.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13010-e13010
Author(s):  
Krishna Mohan V T Mallavarapu ◽  
Santa Ayyagari ◽  
Senthil Jagannathan Rajappa ◽  
Krishnam Raju Alluri ◽  
Sudha Murthy S
Keyword(s):  
Overall Survival ◽  
Treatment Outcomes ◽  
Treatment Protocol ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Single Center Experience ◽  
Dose Methotrexate

e13010 Background: Primary CNS Lymphoma (PCNSL) is a rare neoplasm of the brain accounting for 1-2% of all brain tumours. Incidence and histopathologic features of PCNSL in India has been reported; however, reports on therapy outcomes of the disease are lacking. We report treatment outcomes of patients with PCNSL at our institute. Methods: Case records of all patients treated for PCNSL between 2008 and 2012 were retrospectively analysed. Epidemiologic details, treatments given, progression free and overall survival were calculated. Patients who completed at least high dose methotrexate (1.5 gram/ m2) for 5 courses with or without RT were included for analysis. Overall survival (OS) was defined as time from diagnosis till death/lost to follow up. Results: A total of seventeen patients were analysed. The median age at diagnosis was 58 years and M: F ratio was 1.14:1. Thirteen out of seventeen patients were eligible for analysis; six could complete the total treatment protocol which included methotrexate, vincristine, procarbazine, Dexamethasone, Radiation therapy followed by high dose cytarabine. Median overall survival was 20 months (range 2-54 months). Among those who completed the protocol, median survival at 21 months was not reached with 66% survival. Conclusions: Treatment of PCNSL with at least high dose methotrexate with or without whole brain radiation offers moderate results. Completion of treatment protocol is associated with better overall survival.

Efficacy and safety of anti-VEGF therapy in metastatic unresectable hepatocellular carcinoma: A meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15632-e15632
Author(s):  
Lakshmi Manogna Chintalacheruvu ◽  
Avanija Buddam ◽  
Arun Kanmanthareddy ◽  
Apar Kishor Ganti
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Adverse Effects ◽  
Disease Progression ◽  
Meta Analysis ◽  
Categorical Variables ◽  
Vegf Receptor ◽  
Efficacy And Safety ◽  
Unresectable Hepatocellular Carcinoma ◽  
Significant Difference

e15632 Background:Conventional chemotherapy has limited role in metastatic unresectable hepatocellular carcinoma (HCC). Sorafenib is currently approved for metastatic unresectable HCC. We wanted to assess the efficacy and safety of other tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor (VEGF) receptor such as brivanib, linifanib and regorafenib in metastatic HCC. Methods: We have searched electronic databases Pubmed, Google scholar to identify published trials using brivanib, linifanib and regorafenib in HCC. The outcomes evaluated were overall survival, time to disease progression (TTDP) and adverse effects. Hazard ratios (HR) with their respective 95% confidence intervals (CI) were then computed using the appropriate model for categorical variables. We used STATA 13.0 and Comprehensive Meta Analysis 2.0 software for all analyses. Results: We included seven randomized control studies. A combined analysis of these seven randomised control trials showed improved overall survival (OS) in VEGF-TKI group when compared to placebo HR - 0.79; (95% CI 0.62-1.00). However, there was no significant survival benefit of the newer VEGF receptor inhibitors when compared to sorafenib (HR - 1.05; 95% CI 0.95-1.17). The time to disease progression (TTDP) was significantly better in VEGF-TKI group as compared to placebo (HR - 0.61; 95% CI 0.39-0.97). However, there was no significant difference in TTDP between VEGF-TKI group and Sorafenib (HR - 0.88; 95% CI 0.66-1.16). Adverse effects were noted to be higher in VEGF-TKI group when compared to placebo (HR- 1.07; 95% CI 1.01-1.13). Conclusions: Treatment with TKI targeting VEGF receptor is associated with a significant improvement in OS and TTDP with tolerable side effect profile. Inhibiting the VEGF receptor pathway could lead to improved outcomes in HCC.

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