pirarubicin and Brain-Neoplasms

Three pediatric patients with infratentorial metastatic non-epithelial malignant brain tumors were successfully treated by radical surgical resection followed by aggressive radiochemotherapy. One patient with neuroblastoma and two with rhabdomyosarcoma were successfully treated by first line multimodal treatments, but developed infratentorial metastasis after several months of remission. All patients revealed intracranial metastases manifesting as rapidly progressing neurological symptoms caused by mass effect in the posterior fossa. Radical surgical resection was performed without morbidity. The patients were then treated by adjuvant radiochemotherapy with or without autologous peripheral blood stem cell transplantation, resulting in complete remission. Two patients developed extracranial recurrences 4 months after the treatments for intracranial metastases. One patient was treated by second high-dose chemotherapy with allogeneic cord blood transplantation, again resulting in complete remission. Another patient was treated by second chemotherapy and maintaining stable disease. The other patient maintained complete remission. All three patients were alive without neurological deficit for 8, 11, and 12 months after diagnosis of brain metastasis. Patients with infratentorial brain metastases of highly malignant pediatric non-epithelial tumors are in a severe clinical state, but still can have longer and useful lives with aggressive multimodal treatments combined with radical surgical resection.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Camptothecin; Carboplatin; Chemotherapy, Adjuvant; Child; Child, Preschool; Cisplatin; Combined Modality Therapy; Dactinomycin; Doxorubicin; Etoposide; Humans; Ifosfamide; Infant; Infratentorial Neoplasms; Irinotecan; Melphalan; Neoplasm Metastasis; Neuroblastoma; Rhabdomyosarcoma; Thiotepa; Topotecan; Vincristine

The present paper investigates the pharmacokinetics of pirarubicin (THP) in the plasma and cerebrospinal fluid (CSF) of two patients with glioma during hyperosmotic disruption of the blood-brain barrier (HODBBB) and intra-arterial combination chemotherapy. A 42-year-old Japanese man (patient A) with glioblastoma and a 21-year-old Japanese woman (patient B) with astrocytoma received a course of HODBBB and intra-arterial combination chemotherapy with THP, methotrexate, peplomycin, and vindesine. Patient A was initially administered mannitol, followed by the infusion of anticancer drugs into the right internal carotid artery. Patient B was initially administered mannitol, followed by the infusion of anticancer drugs into the right internal carotid artery and, immediately thereafter, into the right vertebral artery. Samples of blood and of CSF in the brain ventricle were obtained. THP concentration was measured by HPLC, and the pharmacokinetic parameters of this drug were estimated in plasma and CSF. In both patients, the plasma concentration of THP peaked at the end of infusion, then decreased in a bi-exponential decay pattern during the remainder of the treatment period. THP was detectable in CSF beginning 1.0 h after the initiation of infusion, then was slowly eliminated from the ventricle. The maximum CSF concentration of THP was 0.97% of plasma in patient A and 0.89% in patient B. The CSF AUC of THP was 28.4% of plasma in patient A and 13.1% in patient B.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Blood-Brain Barrier; Brain Neoplasms; Doxorubicin; Female; Glioma; Humans; Infusions, Intra-Arterial; Methotrexate; Peplomycin; Vindesine

The patient was a 2-year-old who was admitted with the diagnosis of liver tumor. The diagnosis at admission was stage III A hepatoblastoma complicated with tumor thrombosis of portal vein. Soon after the admission, the patient's general condition became deteriorated with increased ascites and severer jaundice. As the patient was considered to be in oncogenic emergency, chemotherapy with systemic administration of ADR and CDDP was started. Despite decreases in tumor marker and tumor shrinkage on imaging examinations, tachycardia and arrythmia occurred from the end of the second course of chemotherapy, suggesting ADR-induced cardiomyopathy, when the systemic administration of ADR was switched to less cardiotoxic hepatic arterial infusion of THP-ADR. Following 13 courses of intra-arterial infusion with the total dose of THP-ADR of 200 mg/m2, the tumor was found to have reduced markably in size and thus surgical resection of the tumor was performed. Our experience of this case indicates that, considering the pharmacokinetics and side effects, THP-ADR should be a very effective anti-tumor agent for intra-arterial hepatic infusion. The patient died 10 months after surgery because of multiple metastases into the brain and lungs.

Topics: Antibiotics, Antineoplastic; Brain Neoplasms; Child, Preschool; Doxorubicin; Drug Administration Schedule; Hepatic Artery; Hepatoblastoma; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Lung Neoplasms; Male