Jun Muto1,2,3, Tomoo Matsutani4, Ryosuke Matsuda5, Masashi Kinoshita6, Mitsuteru Oikawa7, Johan Pallud8,9,10, Hikaru Sasaki2. 1. Department of Neurosurgery, Fujita Health University, Japan. 2. Department of Neurosurgery, Keio University School of Medicine, Japan. 3. Department of Neurosurgery, Saiseikai Utsunomiya Hospital, Japan. 4. Department of Neurosurgery, Chiba University, Japan. 5. Department of Neurosurgery, Nara Medical University, Japan. 6. Department of Neurosurgery, Kanazawa University, Japan. 7. Department of Neurosurgery, Nakamura Memorial Hospital, Japan. 8. Department of Neurosurgery, Sainte-Anne Hospital, Paris, France. 9. Paris Descartes University, Sorbonne Paris Cité, France. 10. Inserm, U894, IMA-Brain, Centre de Psychiatrie et Neurosciences, Paris, France.
Abstract
BACKGROUND: The pharmacokinetics of temozolomide (TMZ) in patients with severe renal impairments (creatinine clearance, <36 mL/min/m2) or in hemodialysis (HD) patients has not been investigated. TMZ and its metabolic products are mainly excreted in urine, as retention of these in the body may result in increased adverse events in HD patients. METHODS: Seven HD patients with high-grade gliomas from 6 institutions were included in the study. Patient characteristics, treatment schedule, clinical course, pathological/molecular findings, and adverse events were evaluated. RESULTS: The histopathological diagnoses were isocitrate dehydrogenase (IDH) wild-type glioblastoma in 4 cases, not other specified (NOS) glioblastoma in 2 cases, and IDH-mutant anaplastic astrocytoma in 1 case. Five of the 7 patients completed radiotherapy (48-60 Gy) with concomitant TMZ (75 mg/m2) followed by adjuvant 5-day TMZ (150 mg/m2) every 28 days. During the entire course of treatment with TMZ, severe (Common Terminology Criteria for Adverse Events [CTCAE] ≥ Grade 3) lymphocytopenia occurred in 57%, neutropenia in 0%, and thrombocytopenia in 14% of the patients. Generally, the frequency and degree of myelosuppression do not increase in HD patients with high-grade gliomas. Two of the 7 (28.5%) patients died of infectious disease despite having no direct correlation to myelosuppression; that is similar to the death rate of 21.9% resulting from infection in HD patients in Japan. CONCLUSIONS: Decreasing the dose of TMZ might not be required in HD patients with high-grade gliomas during concomitant radiochemotherapy and maintenance therapy. However, careful clinical and hematological observation is required to avoid critical hematotoxicity and infection.
BACKGROUND: The pharmacokinetics of temozolomide (TMZ) in patients with severe renal impairments (creatinine clearance, <36 mL/min/m2) or in hemodialysis (HD) patients has not been investigated. TMZ and its metabolic products are mainly excreted in urine, as retention of these in the body may result in increased adverse events in HD patients. METHODS: Seven HD patients with high-grade gliomas from 6 institutions were included in the study. Patient characteristics, treatment schedule, clinical course, pathological/molecular findings, and adverse events were evaluated. RESULTS: The histopathological diagnoses were isocitrate dehydrogenase (IDH) wild-type glioblastoma in 4 cases, not other specified (NOS) glioblastoma in 2 cases, and IDH-mutant anaplastic astrocytoma in 1 case. Five of the 7 patients completed radiotherapy (48-60 Gy) with concomitant TMZ (75 mg/m2) followed by adjuvant 5-day TMZ (150 mg/m2) every 28 days. During the entire course of treatment with TMZ, severe (Common Terminology Criteria for Adverse Events [CTCAE] ≥ Grade 3) lymphocytopenia occurred in 57%, neutropenia in 0%, and thrombocytopenia in 14% of the patients. Generally, the frequency and degree of myelosuppression do not increase in HD patients with high-grade gliomas. Two of the 7 (28.5%) patients died of infectious disease despite having no direct correlation to myelosuppression; that is similar to the death rate of 21.9% resulting from infection in HD patients in Japan. CONCLUSIONS: Decreasing the dose of TMZ might not be required in HD patients with high-grade gliomas during concomitant radiochemotherapy and maintenance therapy. However, careful clinical and hematological observation is required to avoid critical hematotoxicity and infection.
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