THERAPY 15

Individualised methotrexate dose improves outcome in ALL

Adjusting the dose of methotrexate in children with B-lineage acute lymphoblastic leukaemia (ALL) to account for the patient's ability to clear the drug, significantly improves outcome without increasing toxicity, say researchers in the US.

In this study, 182 children (aged 4 months to 18 years) with ALL in complete remission following induction therapy, were randomised to receive continuation therapy with either conventional or individualised doses of methotrexate, teniposide and cytarabine. *

Median doses of therapy in the individualised­treatment group were IV methotrexate 1992 mg/m2, IV teniposide 245 mg/m2 and IV cytarabine375 mg/m2 (n = 91); doses were adjusted according to the systemic drug clearance in each patient. In the conventional­treatment group patients received methotrexate 1502 mg/m2, teniposide 200 mg/m2 and cytarabine 300 mg/m2 (91); these doses were based on the patient's body surface area.

The estimated 5-year overall survival rate was 83% and the event-free survival rate was 67%. The estimates of continuous complete remission at 5 years were 72 and 66% in the individualised­and conventional-treatment groups, respectively.

Individualised-treatment recipients had a significantly lower proportion of treatment courses during which systemic exposures were below the target range, compared with conventional-treatment recipients. * * Better outcome in B-lineage leukaemia

Patients with B-lineage leukaemia in the individualised-treatment group had a significantly better outcome than those who received conventional therapy; at 5 years, the rates of continuous complete remission were 76 and 66%, respectively. In patients with T-lineage leukaemia there was no significant difference in terms of outcome between those who received individualised treatment and those who received conventional treatment.

Among patients with B-lineage leukaemia the risk of relapse was significantly associated with the systemic exposure to methotrexate and the proportion of courses with systemic exposure above the target threshold. The risk of relapse was not related to the systemic exposure to teniposide or cytarabine.

Overall, there was no between-group difference in the number of severe toxic effects apart from a higher rate of grade 3 or 4 infections after tenoposide plus cytarabine courses in the individualised-treatment group, compared with the conventional-treatment group.

* Patients received abemale doses ofhigh-dose methot1T!XOle and teniposide plus cyta:rabine every 6 weeksfor 55 weeks. In addition, they received doily orol merr:aptopurine 75 mglrril and weekly parmteral meJhotrexote 40 mgmr in the 5-week intervals between the abemale meJhotrexote and teniposide plus cyta:rabine dosing. From weeks 60 to 120, therapy comprised only doily orol men:aptopurine and weekly parmteral methotrexaJe. ** The target rangesfor systemic e:xposure in the indMduaIised­treatmenJ group were 5lKJ-950 ~for methotrexaIe, 300-525 ~

1173-832419811126-000151$01.000 Adl. International Limited 1998. All rlghtll reeerved

for teniposide, and 22.5-(j() ~for cytaTabine.

Evans WE. Relling MY, Rodman JH, Crom WR, Boyett 1M, et al. Conventional compared with individualized chemotherapy for cbildhood acute lymphoblastic leukemia New England Journal of Medicine 338: 499-505. 19 Feb 1998 800642380

Inphannae 28 Feb 1998 No. 1126