Preliminary individual adjuvant chemotherapy for primary central nervous system lymphomas based on the expression of drug-resistance genes.
Individual adjuvant chemotherapy based on the expression of drug-resistance genes by reverse transcription-polymerase chain reaction (RT-PCR) was applied for the treatment of patients with primary central nervous system lymphoma (PCNSL). Three patients were included in this study. The drug-resistance genes were investigated in tumor tissues by RT-PCR with the specific primers for MDR-1, MRP-1, MRP-2, MXR-1, MGMT, GST-pei, and topoisomerase II alpha. We selected proper anticancer agents based on mRNA expression of these drug-resistance genes. In case 1, RT-PCR showed overexpression of MDR-1, MRP-1, MGMT, and topoisomerase II alpha mRNA, whereas neither MRP-2, MXR-1, nor GST-pei was expressed. The patient was given high-dose methotrexate (HD-MTX) for the first cycle of treatment; however, the reduced tumor showed regrowth before the second cycle of treatment, and therefore the patient was given carboplatin, mitoxantrone, and HD-MTX in the second and third cycles. Finally, magnetic resonance (MR) images showed a complete response. The other two cases showed similar patterns of drug-resistance gene expression, such that mRNAs of MRP-2, MXR-1, MGMT, GST-pei, and topoisomerase II alpha were overexpressed, whereas neither MDR-1 nor MRP-1 was expressed. They were successfully treated with combined HD-MTX and CHOP (cyclophosphamide, doxorubicin, vincristine, and predonsone). Our preliminary trial of individual adjuvant chemotherapy based on RT-PCR suggested that it was an effective and beneficial therapy for PCNSL. Although HD-MTX therapy is supposed to be effective for patients with MDR-1-negative PCNSL, MTX alone should be avoided in the choice of the anticancer drug for the treatment of MDR-1-positive PCNSL.
Kunishio
Katsuzo
K
Department of Neurosurgery, Kawasaki Hospital, Okayama, 2-1-80 Nakasange, Okayama 700-8505, Japan. katsuzo@k9.dion.ne.jp
Okada
Masaki
M
Matsumoto
Yoshihito
Y
Nagao
Seigo
S
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D019450:Genes, MDR / Q000502:physiology; D006801:Humans; D008223:Lymphoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D011859:Radiography; D020133:Reverse Transcriptase Polymerase Chain Reaction
C000715087:ABCC2 protein, human; D000089762:Multidrug Resistance-Associated Protein 2; D008727:Methotrexate