scholarly journals Imatinib mesylate treatment for platelet-derived growth factor receptor alfa-positive choroid plexus carcinoma

2012 ◽  
Vol 2 (2) ◽  
pp. 49 ◽  
Author(s):  
Chihiro Kawakami ◽  
Akiko Inoue ◽  
Kimitaka Takitani ◽  
Motomu Tsuji ◽  
Kimiko Wakai ◽  
...  
Keyword(s):  
Growth Factor ◽  
Choroid Plexus ◽  
Standard Dose ◽  
Growth Factor Receptor ◽  
Female Child ◽  
Disease Recurrence ◽  
Choroid Plexus Carcinoma ◽  
High Dose ◽  
Imatinib Treatment ◽  
Stem Cell Rescue

We herein report a female child with choroid plexus carcinoma treated with standard dose of imatinib at disease recurrence. This patient failed initial twice-surgical resections, central nervous system (CNS) irradiation, and adjuvant chemotherapies and high-dose thiotepa and melphalan with auto peripheral blood stem cell rescue. Finally, imatinib treatment was undergone as a palliative setting, however the tumor did not reduce and the patient died of tumor bleedings. We consider that the reasons for the failure are as follows: i) adequate CNS level of imatinib were not obtained because of the blood brain barrier, ii) the lack of plateletderived growth factor receptor beta expression in our case may have a crucial role.

scholarly journals ATRT-04. INHERITED RHABDOID PREDISPOSITION SYNDROME: A CASE OF CHOROID PLEXUS CARCINOMA AND ATYPICAL TERATOID RHABDOID TUMOR IN SIBLINGS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii276-iii276
Author(s):  
Alexis Judd ◽  
Erin Wright ◽  
Sarah Rush
Keyword(s):  
Overall Survival ◽  
Choroid Plexus ◽  
Disease Recurrence ◽  
Genetic Alterations ◽  
Rhabdoid Tumor ◽  
Choroid Plexus Carcinoma ◽  
High Dose ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Increased Risk ◽  
Atypical Teratoid

Abstract Choroid plexus carcinoma (CPC) and Atypical teratoid/rhabdoid tumor (ATRT) are aggressive, malignant brain cancers most commonly arising in children less than 3 years of age. These tumors often have genetic alterations in the tumor suppressor gene SMARCB1/INI1. Rhabdoid predisposition syndrome (RTPS) categorizes patients with germline mutations in SMARCB1 or SMARCA4, leading to a markedly increased risk of developing rhabdoid tumors. Both CPC and ATRT have been demonstrated in patients with these rhabdoid predisposition syndromes. In general, these tumors tend to have a poor prognosis. However, with the presence of a SMARCB1 mutation they may have improved overall survival. We present two interesting cases of siblings with maternally inherited SMARCB1 mutations: one a 21-month-old male who presented with an ATRT and another a 10 month old female who presented with a CPC. The ATRT was treated as per the Children’s Oncology Group study ACNS0333 with high dose chemotherapy and stem cell rescue as well as cranial radiation. The CPC was treated as per CPT-SIOP 2009 with etoposide, cyclophosphamide and vincristine. Unlike other patients with these aggressive tumors, both of these patients are alive without evidence of disease recurrence 8 and 7 years post therapy, respectively. Additional genomic testing on both tumors is currently pending in order to potentially identify other mutations that may impact survival. These cases further illustrate the similar profile of two very different tumors with improved overall survival that may be secondary to mutations in SMARCB1 in RTPS.

scholarly journals RARE-31. RECURRENT CHOROID PLEXUS CARCINOMA IN THE SETTING OF LI-FRAUMENI SYNDROME: REPORT OF TWO CHILDREN MANAGED WITH INTENSIVE RE-INDUCTION AND MARROW-ABLATIVE CONSOLIDATION CHEMOTHERAPY WITHOUT IRRADIATION FOLLOWED BY MOLECULARLY-TARGETED BIOLOGICAL THERAPY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii448-iii449
Author(s):  
Margaret Shatara ◽  
Iwona Filipek ◽  
Maciej Ciołkowski ◽  
Paweł Kowalczyk ◽  
Diana S Osorio ◽  
...  
Keyword(s):  
Choroid Plexus ◽  
Biological Therapy ◽  
De Novo ◽  
Standard Dose ◽  
Disease Patient ◽  
Choroid Plexus Carcinoma ◽  
High Dose ◽  
Unrelated Donor ◽  
Standard Chemotherapy ◽  
Total Resection

Abstract BACKGROUND The optimal management for children with recurrent choroid plexus carcinoma (CPC), is not established. We report two children with germline TP53 mutations, whose CPC relapses were managed with marrow-ablative chemotherapy and oral biologically-targeted therapies. PATIENTS: Patient A: A 17 months old male presented with non-metastatic bilateral CPC. A de novo mosaic germline TP53 mutation was identified. After near-total resections, 16 months of standard chemotherapy were administered; 18 months later, localized tumor growth developed, again near-totally resected. Two cycles of re-induction chemotherapy were administered followed by three cycles of thiotepa/carboplatin with autologous hematopoietic cell rescue (AuHCR) and subsequently 21 months of sirolimus and thalidomide, continuing without residual or recurrent disease. Patient B: A 30 months old male presented with left lateral ventricular non-metastatic CPC. A de novo TP53 germline mutation was identified. Following sub-total resection, craniospinal irradiation with boost was administered followed by eight cycles of standard chemotherapy; 18 months later, localized recurrence developed; gross total resection was followed by 15 months of standard dose chemotherapies; four months thereafter, a second local recurrence developed, again gross totally resected. He then received one cycle of high-dose cyclophosphamide followed by three cycles of thiotepa/carboplatin with AuHCR. Subsequently he received sirolimus and thalidomide for 12 months, complicated by progressive pancytopenia. A small localized CPC recurrence was noted, gross totally resected, concomitant with myelodysplastic syndrome; he underwent an allogeneic matched unrelated donor marrow transplantation. CONCLUSIONS Marrow-ablative chemotherapy with post-transplant targeted biological therapy may afford durable survival for select children with recurrent CPC.

scholarly journals Evaluation of Morphine with Imiquimod as Opioid Growth Factor Receptor or Nalmefene as Opioid Blocking Drug on Leishmaniasis Caused by Leishmania major in Vitro

2019 ◽  
Author(s):  
Javad JABARI ◽  
Fatemeh GHAFFARIFAR ◽  
John HORTON ◽  
Abdolhosein DALIMI ◽  
Zohreh SHARIFI
Keyword(s):  
Flow Cytometry ◽  
Growth Factor ◽  
Leishmania Major ◽  
Growth Factor Receptor ◽  
Adjunctive Treatment ◽  
Control Group ◽  
High Dose ◽  
Macrophage Infection ◽  
Opioid Growth Factor

Background: In this research, the effect of morphine on promastigotes and amastigotes of Leishmania major has been investigated in the presence of nalmefene as a blocking opioid drug and imiquimod as an opioid growth factor receptor. Methods: This study was conducted at Tarbiat Modares University, Tehran, Iran in 2015-2018. Morphine with different concentration (0.1, 1, 10 and 100 1µg/ml) alone and with imiquimod (0.01, 0.1 and 1µg/ml) and nalmefene (0.1, 1 and 10 µg/ml) on promastigotes and amastigotes in macrophages and also the percentage of infected macrophages was investigated. For evaluation of the apoptosis, we used flow cytometry method. The effect of imiquimod and nalmefene on glucantime and amphotericin B as current drugs for treatment of leishmaniasis was evaluated too. Results: The effect of morphine on promastigotes and amastigotes has a reverse relationship with its concentration. The results of flow cytometry for drug-treated promastigotes revealed that apoptosis and necrosis did not increase markedly relative to the control group. A combination of morphine and imiquimod in concentrations of 0.05, 5 and 5 µg/ml had a pronounced effect on reduction and prevention of macrophage infection with amastigotes. Morphine at a concentration of 0.1 µg/ml plays the role of adjunctive treatment. In amastigote assay we found the better results in group that get glucantime 25 µg/ml+ imiquimod 0.5 µg/ml. Conclusion: This effect is strengthened with imiquimod and weakened with nalmefene. Using high dose morphine and nalmefene had reverse effects. They suppress immune system and had no controlling effect in macrophages amastigote infection and reduction of promastigotes.

scholarly journals Multicenter, Prospective, Phase II and Biomarker Study of High-Dose Bevacizumab as Induction Therapy in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannoma

2019 ◽  
Vol 37 (35) ◽  
pp. 3446-3454 ◽  
Author(s):  
Scott R. Plotkin ◽  
Dan G. Duda ◽  
Alona Muzikansky ◽  
Jeffrey Allen ◽  
Jaishri Blakeley ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Growth Factor ◽  
Phase Ii ◽  
Standard Dose ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
High Dose ◽  
Radiographic Response ◽  
Bevacizumab Treatment

PURPOSE Bevacizumab treatment at 7.5 mg/kg every 3 weeks results in improved hearing in approximately 35%-40% of patients with neurofibromatosis type 2 (NF2) and progressive vestibular schwannomas (VSs). However, the optimal dose is unknown. In this multicenter phase II and biomarker study, we evaluated the efficacy and safety of high-dose bevacizumab in pediatric and adult patients with NF2 with progressive VS. PATIENTS AND METHODS Bevacizumab was given for 6 months at 10 mg/kg every 2 weeks, followed by 18 months at 5 mg/kg every 3 weeks. The primary end point was hearing response defined by word recognition score (WRS) at 6 months. Secondary end points included toxicity, radiographic response, quality of life (QOL), and plasma biomarkers. RESULTS Twenty-two participants with NF2 (median age, 23 years) with progressive hearing loss in the target ear (median baseline WRS, 53%) were enrolled. Nine (41%) of 22 participants achieved a hearing response at 6 months (1 of 7 children and 8 of 15 adults; P = .08). Radiographic response was seen in 7 (32%) of 22 patients with VS at 6 months (7 of 15 adults and 0 of 7 children; P = .05). Common mild to moderate adverse events included hypertension, fatigue, headache, and irregular menstruation. Improvement in NF2-related QOL and reduction in tinnitus-related distress were reported in 30% and 60% of participants, respectively. Paradoxically, high-dose bevacizumab treatment was not associated with a significant decrease in free vascular endothelial growth factor but was associated with increased carbonic anhydrase IX, hepatocyte growth factor, placental growth factor, stromal cell-derived factor 1α, and basic fibroblast growth factor concentrations in plasma. CONCLUSION High-dose bevacizumab seems to be no more effective than standard-dose bevacizumab for treatment of patients with NF2 with hearing loss. In contrast to adults, pediatric participants did not experience tumor shrinkage. However, adult and pediatric participants reported similar improvement in QOL during induction. Novel approaches using bevacizumab should be considered for children with NF2.

Treatment Patterns and Associated Outcomes in Chronic Phase CML Patients Who Fail Imatinib 400 Mg Daily

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4436-4436
Author(s):  
Jessica M. Scott ◽  
Michael J. Mauro
Keyword(s):  
Research Funding ◽  
Chart Review ◽  
Standard Dose ◽  
Chronic Phase ◽  
Treatment Patterns ◽  
High Dose ◽  
Imatinib Treatment ◽  
Inadequate Response ◽  
Second Line ◽  
Imatinib Resistance

Abstract 4436 INTRODUCTION: For chronic phase (CP-CML) patients failing standard dose (SD) imatinib (400 mg daily) several options remain including higher dose imatinib (600 or 800 mg daily) or switch to another tyrosine kinase inhibitor (TKI). Less often referral for stem cell transplantation or switch to novel therapies via clinical trial options is pursued. There may be differences in response and outcome between patients treated with high dose imatinib, dasatinib, nilotinib, or other therapy following failure of SD imatinib, and those differences may be correlated with the reasons for SD imatinib failure. PURPOSE: This analysis will evaluate the treatment patterns and associated outcomes for patients with chronic myeloid leukemia in CP-CML who failed imatinib 400 mg daily, and analyze potential correlation with the reasons for discontinuation of SD imatinib. METHODS: A 50-patient medical chart review commenced in June 2011 to identify CP-CML patients who received another intervention after failing treatment with SD imatinib. Retrospective adult (≥18 years) subjects were identified who: 1) had been diagnosed with Philadelphia chromosome positive CML in chronic phase, 2) had received imatinib prior to any other TKI, 3) had failed treatment with the standard dose of 400mg daily due to resistance, intolerance, disease progression to accelerated phase (AP) or blast crisis (BC), or inadequate response 4) failed standard dose imatinib after FDA approval of dasatinib and nilotinib for second line use (after Nov 2007) and 5) are followed at the study site (+/− additional community physician management). Retrospective data pertaining to CML diagnosis and imatinib treatment was collected with a goal of 12-month minimum prospective review from time of SD imatinib failure, with a maximal duration of follow-up planned of 4 years post SD imatinib failure. Reasons for failure and subsequent treatment patterns, outcomes were evaluated and descriptive statistical analysis planned. No intervention was involved in this study. RESULTS: To date, chart review has yielded 38 patients who ranged in age from 15 to 70 years of age (mean 45 years) at time of diagnosis. They were 55% male, 45% female and were predominantly white (84%). Sokal score was recorded in 55% of the population and was evenly distributed where recorded (high n=8, intermediate n=6, low n=7). None of the patients progressed to AP or BC during treatment with SD imatinib. Treatment failures were due to inadequate response (40%), resistance (26%), or intolerance (34%). All participants were treated with a TKI as the next intervention following SD imatinib failure, as outlined in Table 1. Of the patients who failed imatinib due to inadequate response, the majority (73%) received high dose imatinib; of those who failed due to resistance a majority received dasatinib (60%) and of those who failed due to intolerance a majority received nilotinib (69%). CONCLUSIONS: Initial analysis demonstrates preference of high dose imatinib or one of the second line TKIs over others in patients who fail imatinib, based on reason for failure. High dose imatinib was more common in cases of inadequate response after SD imatinib; dasatinib was more commonly utilized in the case of SD imatinib resistance. Nilotinib was more commonly used in the case of intolerance to SD imatinib. Assessment of long-term patient outcome is ongoing, and additional cases. Further analysis will include an examination of the toxicity and efficacy of second line therapy, as well as the prognostic factors that influence treatment patterns for CP-CML patients who failed imatinib 400 mg daily. Disclosures: Mauro: Novartis: Research Funding; Bristol Myers Squibb: Research Funding; Ariad: Research Funding.

Sign in / Sign up

Export Citation Format

Share Document