Deleterious impact of a generic temozolomide formulation compared with brand-name product on the kinetic of platelet concentration and survival in newly diagnosed glioblastoma.
Fundam Clin Pharmacol
; 34(4): 484-494, 2020 Aug.
Article
em En
| MEDLINE
| ID: mdl-31994757
ABSTRACT
Chemo-induced thrombocytopenia is a limiting toxicity among patients receiving temozolomide (TMZ) as first-line treatment for glioblastoma. We aimed to compare early platelet concentration kinetics, hematological safety profile, and impact on survival following the initiation of either the brand-name or a generic TMZ formulation. A retrospective trial was conducted in patients suffering from newly diagnosed glioblastoma. Patients were treated with TMZ at 75 mg/m2 per day during six weeks, concomitantly with radiotherapy. Platelet concentration was collected each week. Primary endpoint was to perform a linear mixed-effect model of platelet concentration kinetic over weeks. A total of 147 patients were included as follows 96 received the brand-name TMZ, and 51 received a generic TMZ formulation. Exposition to the generic was a significant variable that negatively influenced the platelet kinetics in the radiotherapy and concomitant TMZ phase, P = 0.02. Grade ≥3 chemo-induced thrombocytopenia was more frequent in the generic group 19.6% [95% CI 8.7-30.5%] vs 3.1% [0-6.6%], P = 0.001. Exposition to the generic formulation of TMZ led to increase early treatment discontinuation due to TMZ-induced thrombocytopenia and was a worsening independent prognostic factor on overall survival adjusted HR 1.83 [1.21-2.8], P = 0.031. These data suggest that exposition to a generic formulation of TMZ vs the brand-name product is associated with higher early platelet decrease leading to clinically relevant impacts on treatment schedule in glioblastoma. Further prospective trials are needed to confirm these results.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Trombocitopenia
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Plaquetas
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Neoplasias Encefálicas
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Medicamentos Genéricos
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Glioblastoma
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Antineoplásicos Alquilantes
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Temozolomida
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article