A POETIC Phase II study of continuous oral everolimus in recurrent, radiographically progressive pediatric low-grade glioma.

Autor: Wright KD; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, Massachusetts, 02215, USA., Yao X; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, Massachusetts, 02215, USA., London WB; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, Massachusetts, 02215, USA., Kao PC; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, Massachusetts, 02215, USA., Gore L; Children's Hospital Colorado, 13123 E 16th Avenue, Aurora, Colorado, 80045, USA., Hunger S; Children's Hospital Colorado, 13123 E 16th Avenue, Aurora, Colorado, 80045, USA., Geyer R; Seattle Children's Hospital, 4800 Sand Point Way NE, Seattle, Washington, 98105, USA., Cohen KJ; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 401 N Broadway, Baltimore, Maryland, 21231, USA., Allen JC; New York University Medical Center, 550 1st Avenue, New York, New York, 10016, USA., Katzenstein HM; Children's Healthcare of Atlanta, 1365 Clifton Road NE, Atlanta, Georgia, 30322, USA., Smith A; University of Florida Health Shands Cancer Hospital, 1515 SW Archer Road, Gainesville, Florida, 32608, USA., Boklan J; Phoenix Children's Hospital, 1919 E Thomas Rd, Phoenix, Arizona, 85016, USA., Nazemi K; OHSU Doernbecher Children's Hospital, 700 SW Campus Drive, Portland, Oregon, 97239, USA., Trippett T; Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA., Karajannis M; Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA., Herzog C; MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA., Destefano J; Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA., Direnzo J; Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA., Pietrantonio J; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, Massachusetts, 02215, USA., Greenspan L; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, Massachusetts, 02215, USA., Cassidy D; Children's Hospital Colorado, 13123 E 16th Avenue, Aurora, Colorado, 80045, USA., Schissel D; Children's Hospital Colorado, 13123 E 16th Avenue, Aurora, Colorado, 80045, USA., Perentesis J; Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio, 45229, USA., Basu M; Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio, 45229, USA., Mizuno T; Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio, 45229, USA., Vinks AA; Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio, 45229, USA., Prabhu SP; Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA., Chi SN; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, Massachusetts, 02215, USA., Kieran MW; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, Massachusetts, 02215, USA.
Jazyk: angličtina
Zdroj: Pediatric blood & cancer [Pediatr Blood Cancer] 2021 Feb; Vol. 68 (2), pp. e28787. Date of Electronic Publication: 2020 Nov 02.
DOI: 10.1002/pbc.28787
Abstrakt: Background: To evaluate efficacy, pharmacokinetics (PK) and pharmacodynamics of single-agent everolimus in pediatric patients with radiographically progressive low-grade glioma (LGG).
Methods: Everolimus was administered at 5 mg/m 2 once daily as a tablet or liquid for a planned 48-week duration or until unacceptable toxicity or disease progression. Patients with neurofibromatosis type 1 were excluded. PK and pharmacodynamic endpoints were assessed in consenting patients.
Results: Twenty-three eligible patients (median age 9.2 years) were enrolled. All patients received prior chemotherapy (median number of prior regimens two) and/or radiotherapy (two patients). By week 48, two patients had a partial response, 10 stable disease, and 11 clinical or radiographic progression; two discontinued study prior to 1 year (toxicity: 1, physician determination: 1). With a median follow up of 1.8 years (range 0.2-6.7 years), the 2-, 3-, and 5-year progression-free survivals (PFS) were 39 ± 11%, 26 ± 11%, and 26 ± 11%, respectively; two patients died of disease. The 2-, 3-, and 5-year overall survival (OS) were all 93 ± 6%. Grade 1 and 2 toxicities predominated; two definitively related grade 3 toxicities (mucositis and neutropenia) occurred. Grade 4 elevation of liver enzymes was possibly related in one patient. Predose blood levels showed substantial variability between patients with 45.5% below and 18.2% above the target range of 5-15 ng/mL. Pharmacodynamic analysis demonstrated significant inhibition in phospho-S6, 4E-BP1, and modulation of c-Myc expression.
Conclusion: Daily oral everolimus provides a well-tolerated, alternative treatment for multiple recurrent, radiographically progressive pediatric LGG. Based on these results, everolimus is being investigated further for this patient population.
(© 2020 Wiley Periodicals LLC.)
Databáze: MEDLINE
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