melphalan and Seizures

Progressive multiple myeloma may manifest features of 'de-differentiation', including a plasmablastic appearance, failure to secrete paraprotein, extramedullary involvement, and resistance to treatment. A 44-year-old woman with kappa-light chain myeloma underwent allogeneic stem cell transplantation (SCT). Twenty months later she developed paraspinal plasmablastic myeloma in the absence of paraprotein in urine or myeloma in the marrow. The paraspinal masses responded to chemotherapy. At 30 months she developed myelomatous meningitis, which proved resistant to intrathecal chemotherapy, irradiation, and donor lymphocyte infusion (DLI). The leptomeningeal disease led to death at 38 months. This is the first report of leptomeningeal relapse of myeloma after allografting.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cell Differentiation; Combined Modality Therapy; Dexamethasone; Diphosphonates; Doxorubicin; Fatal Outcome; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors; Immunosuppressive Agents; Interleukin-2; Melphalan; Meninges; Methotrexate; Multiple Myeloma; Neoplastic Stem Cells; Osteolysis; Pamidronate; Paraparesis; Recurrence; Salvage Therapy; Seizures; Transplantation Conditioning; Transplantation, Homologous; Vincristine

Irinotecan (CPT-11), a water-soluble topoisomerase I inhibitor, is metabolized by carboxylesterase enzymes to form an active metabolite, SN-38. Recent studies have shown that irinotecan also undergoes oxidative metabolism by the P450 isozyme CYP3A4, leading to the formation of a minor inactive metabolite, 7-ethyl-10-[4-N-[(5-aminopentanoic acid)-1-piperidino]-carbonyloxy-camptothecin (APC). The elucidation of this metabolic pathway suggests the potential for drug interactions when irinotecan is administered with other inducers or substrates of CYP3A4. In this report, the authors summarize the pharmacokinetic profile of irinotecan and its major metabolites with and without concomitant phenytoin administration in an individual patient. These studies revealed that concomitant phenytoin administration resulted in a marked decrease in the systemic exposure to irinotecan and SN-38 and an increase in the exposure to APC. The area under the curve of irinotecan and SN-38 decreased by 63% and 60%, respectively; the area under the curve of APC increased by approximately 16%. Further detailed pharmacokinetic studies of irinotecan in patients receiving concomitant therapy with enzyme-inducing anticonvulsants are required so that rational dosing recommendations can be provided for this patient population.

Topics: Adolescent; Anticonvulsants; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Brain Neoplasms; Camptothecin; Carboplatin; Cisplatin; Combined Modality Therapy; Cranial Irradiation; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dexamethasone; Disease Progression; Drug Interactions; Enzyme Induction; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Irinotecan; Male; Melphalan; Mixed Function Oxygenases; Neoplasm Recurrence, Local; Ondansetron; Phenobarbital; Phenytoin; Pineal Gland; Pinealoma; Prodrugs; Salvage Therapy; Seizures

Eighteen patients with poor risk Ewing's sarcoma (including 11 patients with metastatic disease at presentation) received consolidation therapy of busulphan and melphalan with autologous stem cell rescue. There were nine females. The median age at diagnosis was 14.2 years (range 2.75-30 years). There was one early death due to cytomegalovirus pneumonitis. One patient developed a single generalised convulsion during busulphan therapy. Severe renal toxicity was not encountered. One patient developed veno-occlusive disease of the liver (VOD) which eventually resolved. With a median follow up of 2 years, 13 patients survive including six with initial metastatic disease. We conclude that high-dose busulphan/melphalan is well-tolerated and should be evaluated for efficacy in a larger series of patients with high risk Ewing's sarcoma.

Topics: Adolescent; Adult; Anticonvulsants; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Child; Child, Preschool; Clonazepam; Combined Modality Therapy; Contraindications; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Male; Melphalan; Neoplasm Metastasis; Phenytoin; Remission Induction; Sarcoma, Ewing; Seizures; Survival Analysis; Transplantation Conditioning; Treatment Outcome

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Viscosity; Carmustine; Cyclophosphamide; Humans; Hypercalcemia; Male; Melphalan; Multiple Myeloma; Paralysis; Plasmapheresis; Prednisone; Seizures; Serum Globulins; Vincristine

Topics: Alanine; Animals; Anti-Bacterial Agents; Antimetabolites; Azaserine; Behavior, Animal; Central Nervous System; Chlorambucil; Cyclophosphamide; Cysteine; Drug Antagonism; Glycine; Male; Mannitol; Mechlorethamine; Melphalan; Nitrogen Mustard Compounds; Phenobarbital; Phenytoin; Rats; Seizures; Spasm; Thiourea; Triethylenemelamine; Tryptophan