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Phase 2 trial of sorafenib in children and young adults with refractory solid tumors: A report from the Children's Oncology Group
Author(s) -
Kim AeRang,
Widemann Brigitte C.,
Krailo Mark,
Jayaprakash Nalini,
Fox Elizabeth,
Weigel Brenda,
Blaney Susan M.
Publication year - 2015
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.25548
Subject(s) - sorafenib , medicine , rhabdomyosarcoma , hepatocellular carcinoma , response evaluation criteria in solid tumors , wilms' tumor , oncology , refractory (planetary science) , hepatoblastoma , pharmacokinetics , sarcoma , phases of clinical research , toxicity , pathology , physics , astrobiology
Background Sorafenib is an oral small molecule inhibitor of multiple kinases controlling tumor growth and angiogenesis. The purpose of the phase 2 study was to determine the response rate of sorafenib and gain further information on the associated toxicities, pharmacokinetics, and pharmacodynamics of sorafenib in children and young adults with relapsed or refractory tumors including rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma (HCC), and papillary thyroid carcinoma (PTC). Procedure Sorafenib, 200 mg/m 2 /dose, was administered every 12 hr continuously for 28 day cycles using a two‐stage design in two primary strata (rhabdomyosarcoma and Wilms tumor) and two secondary strata (HCC and PTC). Correlative studies in consenting patients included determination of sorafenib steady state trough concentrations and assessments of VEGF and sVEGFR2. Results Twenty patients (median age of 11 years; range, 5–21) enrolled. No objective responses (RECIST) were observed in the 10 evaluable patients enrolled in each of the two primary disease strata of rhabdomyosarcoma and Wilms tumor. No patients with HCC or PTC were enrolled. Sorafenib was not associated with an excessive rate of dose‐limiting toxicity (DLT). The mean ± SD steady state concentration during cycle 1 day 15 was 6.5 ± 3.9 μg/ml (n = 10). Conclusions Sorafenib was well tolerated in children at 200 mg/m 2 /dose twice daily on a continuous regimen with toxicity profile and steady state drug concentrations similar to those previously reported. Single agent sorafenib was inactive in children with recurrent or refractory rhabdomyosarcoma or Wilms tumor. Pediatr Blood Cancer 2015;62:1562–1566. © 2015 Wiley Periodicals, Inc.