Evaluation of temozolomide in a SCID mouse model of human B-cell precursor leukemia.
We used a SCID mouse model of human B-lineage acute lymphoblastic leukemia to examine the antileukemic activity of temozolomide in comparison to as well as in combination with B43-PAP anti-CD19 immunotoxin. One hundred percent of the 20 PBS-treated control mice died of disseminated human B-lineage ALL at 32 to 64 days after the inoculation of 1x10(6) NALM-6 cells, with a median event free survival time of 43 +/- 1 days. Temozolomide, when administered i.p. for 5 consecutive days at a dose level of 411 mg/m2 or as a single 750 mg/m2 bolus dose, elicited significant antileukemic activity and improved survival in this SCID mouse model of human B-lineage ALL. The median survival times were 43 +/- 1 days for PBS-treated mice, 56 +/- 16 days for mice injected with the 5-day temozolomide program, and 64 +/- 15 days for mice treated with a single bolus dose of temozolomide. However, temozolomide was not as effective as B43-PAP. Whereas only 40 +/- 21% of mice treated with temozolomide survived beyond 120 days, B43-PAP treatment resulted in 74 +/- 7% survival in the same model system. The combination of temozolomide with B43-PAP was well tolerated by mice but it was not significantly more effective than B43-PAP alone. Temozolomide may have very limited potential as an antileukemic agent for treatment of B-lineage ALL.
Messinger
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Y
Parker Hughes Cancer Center, Department of Experimental Oncology, Hughes Institute, St. Paul, MN 55113, USA.
Reaman
G H
GH
Ek
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Uckun
F M
FM
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002051:Burkitt Lymphoma / Q000188:drug therapy*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000627:therapeutic use*; D054789:Ribosome Inactivating Proteins, Type 1; D000077204:Temozolomide; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D003606:Dacarbazine; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein; D000077204:Temozolomide