دورية أكاديمية
A phase I trial of lenalidomide and radiotherapy in children with diffuse intrinsic pontine gliomas or high-grade gliomas.
| العنوان: | A phase I trial of lenalidomide and radiotherapy in children with diffuse intrinsic pontine gliomas or high-grade gliomas. |
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| المؤلفون: | Hipp SJ; Brooke Army Medical Center, 3551 Roger Brooke Drive, Fort Sam Houston, TX, 78234, USA. sean.j.hipp.mil@mail.mil., Goldman S; Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA., Kaushal A; Department of Radiation Medicine, University of Kentucky College of Medicine, Lexington, KY, USA., Krauze A; Division of Radiation Oncology and Developmental Radiotherapeutics, University of British Columbia, Vancouver, BC, Canada., Citrin D; Radiation Oncology Branch, National Cancer Institute at the National Institutes of Health, Bethesda, MD, USA., Glod J; National Cancer Institute at the National Institutes of Health, Bethesda, MD, USA., Walker K; National Cancer Institute at the National Institutes of Health, Bethesda, MD, USA., Shih JH; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Sethumadhavan H; National Cancer Institute at the National Institutes of Health, Bethesda, MD, USA., O'Neill K; National Cancer Institute at the National Institutes of Health, Bethesda, MD, USA., Garvin JH; Columbia University Med Center, New York, NY, USA., Glade-Bender J; Columbia University Med Center, New York, NY, USA.; Memorial Sloan Kettering Cancer Center, New York, NY, USA., Karajannis MA; Memorial Sloan Kettering Cancer Center, New York, NY, USA.; New York University Langone Medical Center, New York, NY, USA., Atlas MP; The Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park, NY, USA., Odabas A; National Cancer Institute at the National Institutes of Health, Bethesda, MD, USA., Rodgers LT; National Cancer Institute at the National Institutes of Health, Bethesda, MD, USA., Peer CJ; Clinical Pharmacology Program, National Cancer Institute at the National Institutes of Health, Bethesda, MD, USA., Savage J; Radiation Oncology Branch, National Cancer Institute at the National Institutes of Health, Bethesda, MD, USA., Camphausen KA; Radiation Oncology Branch, National Cancer Institute at the National Institutes of Health, Bethesda, MD, USA., Packer RJ; Children's National Hospital, Washington, DC, USA., Figg WD; National Cancer Institute at the National Institutes of Health, Bethesda, MD, USA., Warren KE; National Cancer Institute at the National Institutes of Health, Bethesda, MD, USA.; Dana Farber Cancer Institute, Boston, MA, USA. |
| المصدر: | Journal of neuro-oncology [J Neurooncol] 2020 Sep; Vol. 149 (3), pp. 437-445. Date of Electronic Publication: 2020 Oct 11. |
| نوع المنشور: | Clinical Trial, Phase I; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Country of Publication: United States NLM ID: 8309335 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7373 (Electronic) Linking ISSN: 0167594X NLM ISO Abbreviation: J Neurooncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2005- : New York : Springer Original Publication: Boston : M. Nijhoff, 1983- |
| مواضيع طبية MeSH: | Angiogenesis Inhibitors/*therapeutic use , Brain Stem Neoplasms/*therapy , Chemoradiotherapy/*methods , Diffuse Intrinsic Pontine Glioma/*therapy , Lenalidomide/*therapeutic use, Adolescent ; Adult ; Angiogenesis Inhibitors/pharmacokinetics ; Brain Stem Neoplasms/pathology ; Child ; Child, Preschool ; Diffuse Intrinsic Pontine Glioma/pathology ; Female ; Follow-Up Studies ; Humans ; Lenalidomide/pharmacokinetics ; Male ; Maximum Tolerated Dose ; Prognosis ; Tissue Distribution ; Young Adult |
| مستخلص: | Purpose: This study was performed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the immunomodulatory agent, lenalidomide, when administered daily during 6 weeks of radiation therapy to children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG) PATIENTS & METHODS: Children and young adults < 22 years of age with newly diagnosed disease and no prior chemotherapy or radiation therapy were eligible. Children with HGG were required to have an inoperable or incompletely resected tumor. Eligible patients received standard radiation therapy to a prescription dose of 54-59.4 Gy, with concurrent administration of lenalidomide daily during radiation therapy in a standard 3 + 3 Phase I dose escalation design. Following completion of radiation therapy, patients had a 2-week break followed by maintenance lenalidomide at 116 mg/m 2 /day × 21 days of a 28-day cycle. Results: Twenty-nine patients (age range 4-19 years) were enrolled; 24 were evaluable for dose finding (DIPG, n = 13; HGG, n = 11). The MTD was not reached at doses of lenalidomide up to 116 mg/m 2 /day. Exceptional responses were noted in DIPG and malignant glioma (gliomatosis cerebri) notably at higher dose levels and at higher steady state plasma concentrations. The primary toxicity was myelosuppression. Conclusion: The RP2D of lenalidomide administered daily during radiation therapy is 116 mg/m 2 /day. Children with malignant gliomas tolerate much higher doses of lenalidomide during radiation therapy compared to adults. This finding is critical as activity was observed primarily at higher dose levels suggesting a dose response. |
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| معلومات مُعتمدة: | P30 CA008748 United States CA NCI NIH HHS; ZIC SC006537 United States ImNIH Intramural NIH HHS; ZIC SC 006537 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: Diffuse intrinsic pontine glioma; High grade glioma; Lenalidomide; Pediatric neuro-oncology; Radiation |
| المشرفين على المادة: | 0 (Angiogenesis Inhibitors) F0P408N6V4 (Lenalidomide) |
| تواريخ الأحداث: | Date Created: 20201011 Date Completed: 20210819 Latest Revision: 20211012 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC7690216 |
| DOI: | 10.1007/s11060-020-03627-0 |
| PMID: | 33040274 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1573-7373 |
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| DOI: | 10.1007/s11060-020-03627-0 |