The epipodophyllotoxin VP16-213 in combination chemotherapy for adults with acute nonlymphoblastic leukaemia.

A total of 232 previously untreated adults with acute nonlymphoblastic leukaemia were consecutively entered into four successive studies. In the first, complete remission rates and survival were inferior to a group treated on the same regimen in London, suggesting population differences, possibly on the basis of late referral and poor nutritional status. In the second study the addition of the epipodophyllotoxin VP16-213 to conventional doses of doxorubicin and cytosine arabinoside improved complete remission rate and median duration of survival. In the third study this induction programme was unchanged and short duration of intensification was compared with an extended period, but no statistically significant difference was demonstrated. In the fourth study, which is currently active, the role of the epipodophyllotoxin VP16-213 (Cape Town Regimen/CTR III) was compared with the same two agents in combination with thioguanine (DAT), but to date no difference in remission rate or survival is evident. Four conclusions are supported by data from these studies. First, the addition of VP16-213 to doxorubicin and cytosine arabinoside improves complete remission rate, prolongs median duration of complete remission and survival, with shortening of the time taken to achieve this status in our population. Second, evidence to date shows no advantage for the DAT programme containing thioguanine over CTR III in which this latter agent is replaced by the epipodophyllotoxin VP16-213. Third, there is no statistically significant difference in survival once patients have achieved complete remission following randomisation to receive 6 months in comparison with 15 months of intensification therapy. Finally, of the previously described prognostic factors, only response to initial chemotherapy has proved significant.(ABSTRACT TRUNCATED AT 250 WORDS)