Steinbuegl, Mona and Nemes, Karolina and Johann, Pascal and Kroencke, Thomas and Tuechert, Stefanie and da Costa, Maria Joao Gil and Ebinger, Martin and Schueller, Ulrich and Sehested, Astrid and Hauser, Peter and Reinhard, Harald and Sumerauer, David and Hettmer, Simone and Jakob, Marcus and Hasselblatt, Martin and Siebert, Reiner and Witt, Olaf and Gerss, Joachim and Kerl, Kornelius and Fruehwald, Michael C. (2021) Clinical evidence for a biological effect of epigenetically active decitabine in relapsed or progressive rhabdoid tumors. PEDIATRIC BLOOD & CANCER, 68 (12): e29267. ISSN 1545-5009, 1545-5017
Full text not available from this repository. (Request a copy)Abstract
Background Refined therapy has helped to improve survival rates in rhabdoid tumors (RT). Prognosis for patients with chemoresistant, recurrent, or progressive RT remains dismal. Although decitabine, an epigenetically active agent, has mainly been evaluated in the management of hematologic malignancies in adults, safety in children has also been demonstrated repeatedly. Materials and methods A retrospective series of patients who received decitabine upon relapse or progression following therapy according to the EU-RHAB regimen is presented. Due to the retrospective nature of analyses, response was defined as measurable regression of at least one lesion on imaging. 850k methylation profiling was done whenever tumor tissue was available. Results A total of 22 patients with RT of any anatomical localization were included. Most patients (19/22) presented with metastases. All received low-dose decitabine with or preceding conventional chemotherapy. Patients received a median of two (1-6) courses of decitabine; 27.3% (6/22) demonstrated a radiological response. Molecular analyses revealed increased methylation levels in tumors from responders. No excessive toxicity was observed. Clinical benefits for responders included eligibility for early phase trials or local therapy. Responders showed prolonged time to progression and overall survival. Due to small sample size, statistical correction for survivorship bias demonstrated no significant effect on survival for responders. Conclusions Patients with RT demonstrate promising signs of antitumor activity after multiagent relapse therapy including decitabine. Analyses of methylation data suggest a specific effect on an epigenetic level. We propose to consider decitabine and other epigenetic drugs as candidates for further clinical investigations in RT.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ATYPICAL TERATOID/RHABDOID TUMORS; PHASE-I; RADIATION SENSITIVITY; COMBINATION THERAPY; PEDIATRIC-PATIENTS; MYELOID-LEUKEMIA; CANCER-PATIENTS; CELL VACCINE; RISK-FACTORS; CHILDREN; ATRT; decitabine; malignant rhabdoid tumor; relapsed and refractory rhabdoid tumors |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Sep 2022 11:53 |
| Last Modified: | 27 Sep 2022 11:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48068 |
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