Phase 1 dose-escalation and pharmacokinetic study of regorafenib in paediatric patients with recurrent or refractory solid malignancies
| Autor: | Lynley V. Marshall, Irene Jiménez, Andrew D.J. Pearson, Udo Mueller, Adriaan Cleton, Bart Ploeger, Michael Teufel, Patricia Maeda, Sarah Schlief, Bruce Morland, Andrea C. Agostinho, Gilles Vassal, Jasmine Kincaide, Birgit Geoerger, Didier Frappaz |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty Adolescent Maximum Tolerated Dose Pyridines Gastroenterology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Refractory Pharmacokinetics Neoplasms Internal medicine Regorafenib Maculopapular rash medicine Humans Exfoliative dermatitis Child Rhabdomyosarcoma business.industry Phenylurea Compounds Infant medicine.disease Clinical trial 030104 developmental biology Oncology chemistry Tolerability Child Preschool 030220 oncology & carcinogenesis medicine.symptom business |
| Zdroj: | European Journal of Cancer. 153:142-152 |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/j.ejca.2021.05.023 |
| Popis: | Background This phase 1 study evaluated safety, pharmacokinetics (PK), maximum tolerated dose (MTD), and antitumour activity of regorafenib in paediatric patients with solid tumours. Patients and methods Patients (aged 6 months to Results Forty-one patients (median age 13 years) received regorafenib (four cohorts: 60–93 mg/m2). Five of 23 evaluable patients experienced dose-limiting toxicities (Grade 4 thrombocytopenia, Grade 3 maculopapular rash, pyrexia, hypertension, and exfoliative dermatitis [each n = 1]). The MTD was defined as 82 mg/m2. The most common Grade ≥3 drug-related TEAE was thrombocytopenia (10%). The incidence and severity of hypertension, diarrhoea, fatigue, hypothyroidism, and hand–foot skin reaction were lower than reported in adults. Regorafenib exposure increased with dose, with substantial overlap because of moderate-to-high interpatient variability. One patient with rhabdomyosarcoma experienced an unconfirmed partial response; 15 patients had stable disease, five for >16 weeks. Conclusions The recommended phase 2 dose of single-agent regorafenib in paediatric patients with solid malignancies is 82 mg/m2. Regorafenib demonstrated acceptable tolerability and preliminary antitumour activity, supporting further investigation in paediatric patients. Clinical trial number NCT02085148. |
| Databáze: | OpenAIRE |
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