Journal of Clinical Oncology, Vol 1, 689-694, Copyright © 1983 by American Society of Clinical Oncology
High-dose cytosine arabinoside in non-Hodgkin's lymphoma
H Kantarjian, B Barlogie, W Plunkett, W Velasquez, P McLaughlin, S Riggs and F Cabanillas
Thirty-two patients with refractory non-Hodgkin's lymphoma were treated
with high-dose cytosine arabinoside (ara-C) given at 2 g/m2 IV over three
hours every 12 hours for 4-8 g/m2/course repeated at three to four week
intervals. There were eight partial responses (29%) and two minor responses
among 28 evaluable patients. The median response duration was 10 weeks
(range, 6-33 weeks). The median survival was significantly prolonged in
responders compared to nonresponders (28 versus 15 weeks; p = 0.03). Two
additional patients treated with 12 g/m2/course died of sepsis and
myelosuppression. The dose-limiting toxicity was myelosuppression, which
was more pronounced in patients with prior extensive radiation therapy and
bone marrow involvement. In vivo measurements of intracellular
concentrations of ara-CTP, the active metabolite of ara-C, showed
significantly higher values in bone marrows with lymphomatous involvement
compared to normal bone marrows (210 versus 95 microM; p = 0.05), probably
indicating a preferential formation and retention of ara-CTP in malignant
cells compared to normal hemopoietic cells. In addition, higher ara-CTP
levels were found in bone marrows that had higher percentages of cells in S
phase.
