Primary central nervous system lymphoma: Phase I evaluation of infusional bromodeoxyuridine with whole brain accelerated fractionation radiation therapy after chemotherapy (Journal article)
Dabaja, B. S./ McLaughlin, P./ Ha, C. S./ Pro, B./ Meyers, C. A./ Seabrooke, L. F./ Wilder, R. B./ Kyritsis, A. P./ Preti, H. A./ Yung, W. K./ Levin, V./ Cabanillas, F./ Cox, J. D.
BACKGROUND: The current study was performed to determine the maximum tolerated dose (MTD), toxicity, and outcome of infusional 5 bromo-2'-deoxyuridine (bromodeoxyuridine; BUdR) given with accelerated fractionation whole brain radiation therapy (WBRT) after chemotherapy for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: Twelve patients with untreated and histologically confirmed PCNSL were entered on the study between 1994 and 1996. Chemotherapy was comprised of one course of IDHAP plus high-dose methotrexate (HD-MTX). IDHAP is comprised of idarubicin at a dose of 1.5 mg/m(2)/day x 4 days intravenously by continuous infusion (i.v. CI), dexamethasone at a dose of 40 mg i.v. on Days 1-5, cytosine arabinoside at a dose of 2000 mg/ m(2) i.v. on Day 5 after cisplatin, and cisplatin at a dose of 25 mg/m(2)/day x 4 days i.v. CI. HD-MTX was given at a dose of 3.5 g/m(2) i.v. between Day 10 and Day 14 after IDHAP. BUdR was given as an i.v. CI over 48 hours, 2-3 days prior to WBRT and then weekly during WBRT. Dose escalation started at 1.5 g/m(2)/day for Cohort 1 with subsequent increments of 0.3 g/m(2)/day. The WBRT dose was 45 grays (Gy) at a dose of 1.5 Gy twice a day, 5 days per week. Neurocognitive testing was performed before, during, and after treatment. RESULTS: Nine of 12 patients entered on the study received BUdR. One of 3 patients in Cohort 1 developed leukoencephalopathy (LEP), a dose-limiting toxicity (DLT), within 2 months of the completion of therapy. Therefore, the next cohort received the same dose level. Because no toxicity was observed in Cohort 2, the third cohort received a BUdR dose of 1.8 g /m(2)/day. Shortly after completing enrollment in Cohort 3, 3 more patients developed LEP, including 2 from Cohort 1 who had received a dose of 1.5 g/m(2)/day. Thus, DLT occurred at a dose of 1.5 g/m(2)/day, the starting level in the current study. As a result, the trial was stopped. Eight of 12 patients achieved a complete response, 3 achieved a partial response, and 1 patient died before response assessment. CONCLUSIONS: Hyperfractionated WBRT with concurrent BUdR after chemotherapy was found to result in modest disease control but has unacceptable neurotoxicity.
|Institution and School/Department of submitter:||Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής|
|Keywords:||Adult,Aged,Antimetabolites, Antineoplastic/administration & dosage/*adverse,effects/*pharmacology,Antineoplastic Combined Chemotherapy Protocols/*therapeutic use,Brain Diseases/chemically induced,Bromodeoxyuridine/administration & dosage/*adverse effects/*pharmacology,Central Nervous System Neoplasms/*drug therapy/pathology/*radiotherapy,Cisplatin/administration & dosage,Combined Modality Therapy,*Cranial Irradiation,Cytarabine/administration & dosage,Dexamethasone/administration & dosage,Dose-Response Relationship, Drug,Female,Humans,Idarubicin/administration & dosage,Infusions, Intravenous,Lymphoma/*drug therapy/pathology/*radiotherapy,Male,Methotrexate/administration & dosage,Middle Aged,Treatment Outcome|
|Appears in Collections:||Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)|
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