scholarly journals Protocol For An Adjuvant Alpha-Fetoprotein-Derived Peptide After Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma: Safety Study

10.2196/17082 ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. e17082
Author(s):  
Akihiro Nomura ◽  
Takeshi Terashima ◽  
Eishiro Mizukoshi ◽  
Masaaki Kitahara ◽  
Toshinori Murayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Safety Profile ◽  
Transarterial Chemoembolization ◽  
Tumor Antigens ◽  
Subcutaneous Administration ◽  
Alpha Fetoprotein ◽  
High Rate ◽  
Health Concern ◽  
Serious Adverse Events

Background Hepatocellular carcinoma (HCC) is a worldwide health concern because of a continued increase in cases globally; furthermore, the prognosis for patients with HCC remains poor. Transarterial chemoembolization (TACE) has been established as the standard of care for the intermediate stage of HCC; however, no therapeutic agents are available to reduce the high rate of recurrence. Objective This study aims to evaluate the safety of alpha-fetoprotein (AFP)-derived peptides for patients with HCC post-TACE. Methods This will be an open-label, single-arm, multicenter study to evaluate the safety of AFP-derived peptides (AFP 357 and AFP 403), which contain histocompatibility antigen-A24-restricted cytotoxic T lymphocyte epitopes from tumor antigens expressed in HCC and is recognized at a high rate by lymphocytes in patients with HCC. Protocol treatment will consist of six courses of the subcutaneous administration of 3 mg each of AFP 357 and AFP 403. A total of 14 patients will be included in this study, the first 6 as a main analysis target group and an additional 8 as an extended cohort from three institutions in Japan. The primary endpoint will be the occurrence of serious adverse events (safety profile). The secondary endpoints will include time to progression, overall survival, completion rate, and adverse events (efficacy profile). Results We have recruited 14 patients with HCC as of December 2019. The final follow-up will be completed by March 2020. Conclusions In this study, we will evaluate the safety profile of AFP-derived peptides for patients with HCC post-TACE. We believe that this study will provide useful information and will help to design a subsequent phase II trial based on the results. Trial Registration Japan Registry of Clinical Trials jRCTs041180155; https://jrct.niph.go.jp/latest-detail/jRCTs041180155 International Registered Report Identifier (IRRID) DERR1-10.2196/17082

scholarly journals Adjuvant Alpha-Fetoprotein-Derived Peptide After Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma: Protocol for a Safety Study (Preprint)

2019 ◽  
Author(s):  
Akihiro Nomura ◽  
Takeshi Terashima ◽  
Eishiro Mizukoshi ◽  
Masaaki Kitahara ◽  
Toshinori Murayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Safety Profile ◽  
Transarterial Chemoembolization ◽  
Tumor Antigens ◽  
Subcutaneous Administration ◽  
Alpha Fetoprotein ◽  
High Rate ◽  
Health Concern ◽  
Serious Adverse Events

BACKGROUND Hepatocellular carcinoma (HCC) is a worldwide health concern because of a continued increase in cases globally; furthermore, the prognosis for patients with HCC remains poor. Transarterial chemoembolization (TACE) has been established as the standard of care for the intermediate stage of HCC; however, no therapeutic agents are available to reduce the high rate of recurrence. OBJECTIVE This study aims to evaluate the safety of alpha-fetoprotein (AFP)-derived peptides for patients with HCC post-TACE. METHODS This will be an open-label, single-arm, multicenter study to evaluate the safety of AFP-derived peptides (AFP 357 and AFP 403), which contain histocompatibility antigen-A24-restricted cytotoxic T lymphocyte epitopes from tumor antigens expressed in HCC and is recognized at a high rate by lymphocytes in patients with HCC. Protocol treatment will consist of six courses of the subcutaneous administration of 3 mg each of AFP 357 and AFP 403. A total of 14 patients will be included in this study, the first 6 as a main analysis target group and an additional 8 as an extended cohort from three institutions in Japan. The primary endpoint will be the occurrence of serious adverse events (safety profile). The secondary endpoints will include time to progression, overall survival, completion rate, and adverse events (efficacy profile). RESULTS We have recruited 14 patients with HCC as of December 2019. The final follow-up will be completed by March 2020. CONCLUSIONS In this study, we will evaluate the safety profile of AFP-derived peptides for patients with HCC post-TACE. We believe that this study will provide useful information and will help to design a subsequent phase II trial based on the results. CLINICALTRIAL Japan Registry of Clinical Trials jRCTs041180155; https://jrct.niph.go.jp/latest-detail/jRCTs041180155 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/17082

scholarly journals Efficacy and safety of combined endoscopic cyanoacrylate injection and balloon-occluded retrograde transvenous occlusion (BRTOcc) of gastrorenal shunts in patients with bleeding gastric fundal varices

2020 ◽  
Author(s):  
Fateh Bazerbachi ◽  
Akira Dobashi ◽  
Swarup Kumar ◽  
Sanjay Misra ◽  
Navtej S Buttar ◽  
...  
Keyword(s):  
Adverse Events ◽  
Gastric Varices ◽  
High Rate ◽  
Efficacy And Safety ◽  
Cyanoacrylate Glue ◽  
Serious Adverse Events ◽  
Gastroesophageal Varices ◽  
Life Threatening ◽  
Glue Embolization

Abstract Background Endoscopic cyanoacrylate (glue) injection of fundal varices may result in life-threatening embolic adverse events through spontaneous gastrorenal shunts (GRSs). Balloon-occluded retrograde transvenous occlusion (BRTOcc) of GRSs during cyanoacrylate injection may prevent serious systemic glue embolization through the shunt. This study aimed to evaluate the efficacy and safety of a combined endoscopic–interventional radiologic (BRTOcc) approach for the treatment of bleeding fundal varices. Methods We retrospectively analysed the data of patients who underwent the combined procedure for acutely bleeding fundal varices between January 2010 and April 2018. Data were extracted for patient demographics, clinical and endoscopic findings, technical details, and adverse events of the endoscopic–BRTOcc approach and patient outcomes. Results We identified 30 patients (13 [43.3%] women; median age 58 [range, 25–92] years) with gastroesophageal varices type 2 (53.3%, 16/30) and isolated gastric varices type 1 (46.7%, 14/30) per Sarin classification, and median clinical and endoscopic follow-up of 151 (range, 4–2,513) days and 98 (range, 3–2,373) days, respectively. The median volume of octyl-cyanoacrylate: Lipiodol injected was 7 (range, 4–22) mL. Procedure-related adverse events occurred in three (10.0%) patients, including transient fever, non-life-threatening pulmonary glue embolism, and an injection-site ulcer bleed. Complete gastric variceal obturation was achieved in 18 of 21 patients (85.7%) at endoscopic follow-up. Delayed variceal rebleeding was confirmed in one patient (3.3%) and suspected in two patients (6.7%). Although no procedure-related deaths occurred, the overall mortality rate was 46.7%, primarily from liver-disease progression and co-morbidities. Conclusion The combined endoscopic–BRTOcc procedure is a relatively safe and effective technique for bleeding fundal varices, with a high rate of variceal obturation and a low rate of serious adverse events.

Stereotactic Body Radiation Therapy as a Salvage Treatment for Single Viable Hepatocellular Carcinoma at the Site of Incomplete Transarterial Chemoembolization

2021 ◽  
Author(s):  
Sumin Lee ◽  
Jinhong Jung ◽  
Jin-hong Park ◽  
So Yeon Kim ◽  
Jonggi Choi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiation Therapy ◽  
Adverse Events ◽  
Transarterial Chemoembolization ◽  
Stereotactic Body Radiation Therapy ◽  
Medical Center ◽  
Salvage Treatment ◽  
Iodized Oil ◽  
Stereotactic Body Radiation

Abstract Background: To evaluate the clinical outcomes of patients who received stereotactic body radiation therapy (SBRT) for single viable hepatocellular carcinoma (HCC) at the site of incomplete transarterial chemoembolization (TACE).Methods: Incomplete TACE was defined as (1) evidence of viable HCC at the site of TACE on follow-up images following one or more consecutive TACEs, (2) no definite tumor staining on celiac angiogram, or (3) no definite iodized oil uptake on post-embolization angiogram or computed tomography. A total of 302 patients were treated between 2012 and 2017 at Asan Medical Center (Seoul, South Korea). Doses of 10–15 Gy per fraction were given over 3–4 consecutive days. Treatment-related adverse events were evaluated according to the common terminology criteria for adverse events, version 4.03.Results: The median follow-up duration was 32.9 months (interquartile range [IQR], 23.6–41.7) and the median tumor size was 2.0 cm (range, 0.7–6.9). The local control (LC) and overall survival rates at 3 years were 91.2% and 72.7%, respectively. 95.4% of the tumors reached complete response (CR) during the entire follow-up period (anyCR). The median interval from SBRT to anyCR was 3.4 months (IQR, 1.9–4.7), and 39.9% and 83.3% of the lesions reached CR at 3- and 6-months after SBRT, respectively. Radiation-induced liver disease was observed in 8 (2.6%) patients. No patients experienced gastroduodenal bleeding within the radiation field.Conclusion: SBRT should be considered a feasible salvage treatment option for HCC after incomplete TACE.

Imfirst: A phase IIIb, safety, single arm study of carboplatin (CB) or cisplatin (CP) plus etoposide (ET) with atezolizumab (ATZ) in patients with untreated extensive-stage small cell lung cancer (ES-SCLC) in Spain—Primary safety results of the induction phase.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8567-8567
Author(s):  
Maria Rosario García Campelo ◽  
Manuel Domine ◽  
Javier De Castro ◽  
Alberto Moreno ◽  
Santiago Ponce Aix ◽  
...  
Keyword(s):  
Adverse Events ◽  
Safety Profile ◽  
Performance Status ◽  
Maintenance Phase ◽  
Tumor Biomarker ◽  
Induction Phase ◽  
Ecog Performance Status ◽  
Serious Adverse Events ◽  
Biomarker Analysis ◽  
Significant Clinical Improvement

8567 Background: Clinical trial (CT) IMpower133 met both primary endpoints and is the first CT to show significant clinical improvement over standard chemotherapy (C) with a good safety profile in first line (1L) ES-SCLC. The addition of ATZ to CB + ET resulted in an OS landmark of 34% and 22% compared to 21% and 16.8% of patients alive at 18 and 24 months respectively versus C. IMfirst evaluates ATZ + CB or CP + ET in a broader patient population than the pivotal study. ECOG Performance status (PS) 2, asymptomatic untreated brain metastases, underlying stable autoimmune diseases and HIV+ pts are eligible. IMfirst also includes the possibility of 6 C induction cycles according to investigator´s choice and consolidation radiotherapy. Methods: To evaluate the safety and efficacy of ATZ added to CB or CP + ET as 1L treatment in an interventional real world setting of ES-SCLC. Exploratory endpoints include tumor biomarker analysis related to ATZ. Results: As of Oct 2020, 117 pts had been enrolled, 105 treated with ATZ + CB + ET and 12 with ATZ + CP + ET. The median age was 65 years (Y) (range 35-89); 84 males; 14 pts (12%) had CNS metastases and 66 pts were current smokers and 50 former smokers, one had never smoked. The PS was 0 in 28 pts (24%), 1 in 75 (64%) and 2 in 14 (12%). The median of cycles of ATZ received was 4 for all the pts (range 1-12) and 2 for the pts (40) in maintenance phase (range 1-8). Number of pts with adverse events (AEs) was 109, 36 with Serious Adverse Events (SAEs) and 63 with AEs. 8 pts had SAEs related to treatment, 4 had adverse events of special interest and 13 pts discontinued the treatment due to AEs: 6 to ATZ, 12 to CB or CP and 10 to ET, 1 patient discontinued ATZ due to a related AE. Table shows the treatment related AEs (TRAEs). No grade 5 TRAEs were reported. Conclusions: IMfirst induction phase analysis confirms the safety profile of ATZ plus C in a broader population of patients. Efficacy, biomarker and further safety analyses will be presented in the future with longer follow up.[Table: see text]

scholarly journals Sorafenib treatment by Child–Pugh score in Latin American patients with hepatocellular carcinoma

2020 ◽  
Vol 16 (31) ◽  
pp. 2511-2520
Author(s):  
Laura L de Guevara ◽  
Lucy Dagher ◽  
Vanessa MV Arruda ◽  
Keiko Nakajima ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Latin American ◽  
Treatment Option ◽  
Real World ◽  
Safety Profile ◽  
Treatment Duration ◽  
Sorafenib Treatment ◽  
Safety And Efficacy ◽  
Grade 3

Aim: To evaluate sorafenib treatment in Latin American patients with unresectable hepatocellular carcinoma in the real-world GIDEON study. Patients & methods: Sorafenib administration, safety and efficacy were analyzed by Child–Pugh status. Results: Of 90 evaluable patients (37% Child–Pugh A, 46% Child–Pugh B and 3% Child–Pugh C at study entry), 97% started sorafenib at 800 mg/day. Patients with Child–Pugh B7 had the longest median treatment duration of sorafenib (33.1 weeks). Sorafenib-related adverse events occurred in 58% of patients with Child–Pugh A (21% grade 3/4) and 46% with Child–Pugh B (7% grade 3/4). Conclusion: Sorafenib had a similar safety profile across patients with Child–Pugh A and B and is a treatment option for both groups.

scholarly journals Invasive Fungal Infections in Infants—Focus on Anidulafungin

2013 ◽  
Vol 7 ◽  
pp. CMPed.S8028 ◽  
Author(s):  
Michael H. Wilke
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Safety Profile ◽  
Fungal Infections ◽  
Case Reports ◽  
Small Body ◽  
Pediatric Intensive Care ◽  
Invasive Fungal Infections ◽  
Serious Adverse Events ◽  
Good Safety Profile

Introduction Invasive fungal infection in pediatric intensive care units (PICU) is a rising challenge. Candida species are the most common microorganisms in these infections. Due to growing resistance against fluconazole, echinocandins are being used for the appropriate therapy. However, the recent IDSA guidelines recommend them only in cases where fluconazole or Amphotericin B cause treatment failure or are contraindicated. In a literature review, the importance of invasive fungal infections in PICU settings and the role of anidulafungin shall be examined. Materials and Methods Articles were retrieved form PubMed covering the years 2000–2012. Various search terms were used. Then the articles were clustered in different types like ‘review,’ ‘pharmacokinetics,’ ‘case reports’ and others. Results From 67 search results, 14 articles were selected. Of these, 7 were related to anidulafungin, while 7 were related to echinocandins or fungal infections in the PICU. Anidulafungin was examined in 4 PK/PD studies where a good safety profile was found. No serious adverse events occurred. The articles reporting risk factors show that central venous catheters, receipt of antibiotics, receipt of parenteral nutrition, and neutropenia are the most important independent risk factors for invasive fungal infections in PICU. Three reviews of antifungal agents show that echinocandins may be useful due to their safety profile; micafungin is the best examined one and further trials are needed. Discussion The published literature on invasive fungal infections in PICU settings has grown over the years. There are only a few articles, however, which are directly related to the use of anidulafungin in this setting. A most recent publication showed good PK/PD dynamics and a good safety profile for anidulafungin. So far, no RCT in the area of invasive candidiasis in infants and neonates has been published. A review of currently registered trials at ClinicalTrials.gov has shown one more trial related to PK/PD and two trials that investigate the use of anidulafungin or anidulafungin in combination with Voriconazole in pediatrics. Conclusion The small body of existing literature on anidulafungin in infants shows success in treatment, no drug-related adverse events, and good pharmacodynamics. A dosing of 0.75 mg/kg/day or 1.5 mg/kg/day is as effective as 50 mg/day or 100 mg/day in adults. More trials on the use in clinical reality of PICU or NICU should follow.

Liver Damage after Transarterial Chemoembolization without Embolizing Agent in Unresectable Hepatocellular Carcinoma

2003 ◽  
Vol 89 (3) ◽  
pp. 285-287 ◽  
Author(s):  
Stefano Puleo ◽  
Letizia Mauro ◽  
Giuseppe Gagliano ◽  
Rosario Lombardo ◽  
Giovanni Li Destri ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transarterial Chemoembolization ◽  
Alpha Fetoprotein ◽  
Total Serum ◽  
Advanced Hepatocellular Carcinoma ◽  
Significant Finding ◽  
Safe Procedure ◽  
Hepatic Functional Reserve ◽  
Neoplastic Tissue ◽  
Functional Reserve

Aim and Background Transarterial chemoembolization represents a therapy for hepatocellular carcinoma, but in cirrhotic patients affected by large or multifocal HCC with poor hepatic functional reserve, the procedure can damage normal parenchyma. We analyzed the effects on hepatic function of a modified chemoembolization consisting of ethiodized oil (Lipiodol Ultra Fluid) and epirubicin without gelatine sponge (C-LIP). Methods Of 90 patients with hepatocellular carcinoma observed from January 1995 to December 1999, 16 with a diagnosis of advanced (large or multifocal) disease underwent 19 C-LIP. The 30th post-C-LIP day was considered as a checkpoint of the biochemical parameters for a possible hepatic failure. The value of alpha-fetoprotein and the clinical finding of ascites were also considered after 30 days. Results Postoperative values of serum aspartate aminotrasferases, as well as alanine aminotransferase, were significantly higher than preoperative values (P = 0.002 and P = 0.019, respectively) (Table 1). In all patients, there was a significant increase in postoperative total serum bilirubin (P = 0.003). Statistical analysis showed a significant finding of postoperative ascites (P = 0.035) and the effectiveness of C-LIP on neoplastic tissue by a decrease of alpha-fetoprotein values at 30 days (P = 0.067). Conclusions Transcatether arterial chemoembolization could represent an effective therapy against multifocal or advanced hepatocellular carcinoma, and its effectiveness is probably not decreased by using a modified procedure without embolizing agent (C-LIP). However, even when performing such a safe procedure, the hepatic functional reserve of the individual patient needs to be accurately evaluated in order to avoid liver failure.

Multicenter observational study of temsirolimus use records conducted under conditions of routine medical practice.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15610-e15610
Author(s):  
Martin Eduardo Richardet ◽  
Raul Sala ◽  
Luis Fein ◽  
Eduardo Arnoldo Richardet
Keyword(s):  
Adverse Events ◽  
Renal Cancer ◽  
Safety Profile ◽  
Clinical Benefit ◽  
Everyday Practice ◽  
Phase Iii ◽  
Cancer Center ◽  
Pivotal Phase ◽  
Serious Adverse Events ◽  
Advanced Renal Cancer

e15610 Background: Sometimes efficacy and toxicity reported in clinical trials differs from what is later found on everyday practice. Temsirolimus was approved in Argentine on 2009. We conducted a study to evaluate the safety profile in advanced renal cancer patients treated with Temsirolimus in everyday practice conditions. Methods: Descriptive, observational, retrospective study of medical records of patients treated with Temsirolimus from 2 Argentinian centers were analyzed at IONC and IOR from April to December 2010. All patients were high risk according to Memorial Sloan Kettering Cancer Center. 50 patients were included, 36% (18) women and 64% (32) men, average age 53.8 years old (20 - 78). Adverse events were assessed based on the NCI CTC v3. Results: No patient showed side effects during or immediately after the infusion, related with the administration of the drug. This study included patients with extensive metastatic disease and multiple factors of adverse prognosis together with short life expectancy. All centers used the standard premedication and dose and no serious adverse events were registered. The most frequent adverse events were anemia, asthenia and mucositis. In all cases adverse events were manageable with support measures or dose reduction. Although more than 80% of patients showed some type of adverse event, the quantity and severity of them were lower than the ones reported in the literature. Disease progression (67.3% of patients) was the most frequent cause of treatment discontinuation. All patients received a dose = 25mg. A total of 52 adverse events were registered. In Terms of efficacy, 46 patients were suitable for analysis. Our rate of clinical benefit (PR 13%+SD 47.8%) is 60.8% , higher than what was reported in the pivotal phase III study (32.1%), this difference could be attributed to our limited sample size. The ORR observed (13%) is similar to the rate reported in the pivotal phase III trial (8.6%. Range 4.8 – 12.4). Conclusions: The treatment with Temsirolimus in patients with advanced renal cancer with poor prognosis factors showed an acceptable safety profile and clinical benefit, taking into account the characteristics of the target population.

Safety profile of poxviral vaccines: NCI experience.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 85-85
Author(s):  
Joseph W. Kim ◽  
Jennifer L. Marte ◽  
Marijo Bilusic ◽  
Nishith K. Singh ◽  
Christopher Ryan Heery ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Safety Profile ◽  
Specific Antigen ◽  
Safety Data ◽  
Treatment Modalities ◽  
Mucin 1 ◽  
Serious Adverse Events ◽  
Scientific Review ◽  
Gm Csf

85 Background: Recombinant poxviruses have been developed as therapeutic cancer vaccines. Here, we report the safety data from NCI clinical trials with poxviral vaccines. Methods: We evaluated all vaccine injections from 215 patients in 8 clinical trials involving poxviral viral vaccines. The Office of Biotechnology Activities, National Cancer Institute (NCI) Institutional Review Board, and NCI Scientific Review Committee approved all of these trials. Vaccines were consisted of recombinant vaccinia and recombinant fowlpox encoded with 3 human costimulatory molecules (TRICOM), and prostate specific antigen (PSA), or carcinoembryonic antigen, and/or mucin-1. Vaccines were administered at doses between 1.2x108 to 2x109 pfu, subcutaneously, in all patients. Twenty-one patients were also vaccinated intra-tumorally. 84 patients also received other concurrent treatment modalities, such as radiation, celecoxib, ipilimumab, samarium-153, or flutamide on 4 of these trials. All 8 clinical trials involved granulocyte-macrophage colony-stimulating factor (GM-CSF) 100mcg, or recombinant fowlpox encoding GM-CSF at 1x 108pfu as an immune adjuvant. Here, we report here the grade 2 or higher adverse events given at least a possible attribution to vaccine. Results: A total of 1,348 poxviral injections were given in 215 patients. No contact transmission, inadvertent inoculation, or any serious adverse events (AEs) related to vaccinia was observed. Below is the summary of proportion of vaccine administrations associated with specific AEs. Conclusions: These data demonstrate a favorable safety profile of the poxviral vaccines at a broad range of doses, routes of administration, in combination with other treatments, and in various tumor types. Clinical trial information: NCT00060528, NCT00096551, NCT00088413, NCT00081848, NCT00113984, NCT00450619, NCT00450463. [Table: see text]

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