Low Dose Ara-C Versus Hydroxyurea with or without Retinoid in Older Patients Not Considered Fit for Intensive Chemotherapy: The UK NCRI AML14 Trial.

There is no adequate treatment for older patients with AML who are not considered fit for intensive chemotherapy who comprise a significant proportion of the AML population. As part of the ongoing NCRI (formerly MRC) AML14 Trial in patients over 60 years patients were randomised to Low Dose Ara-C (20mg bd for 10 days every 4–6 weeks) versus Hydroxycarbamide (Hydroxyurea). Because of preclinical studies showing sensitization to Ara-C, patients were in addition randomised to receive All-transretinoic acid or not (45mgs/m² for 60 days).

Two hundred and four patients entered; 129 had a WHO score of <2; 155 patients were >65 yrs; 108 had do novo, 53 secondary disease and 28 had high risk MDS (blasts >10%). One hundred and ninety-nine patients entered the HU vs LD-Ara-C randomisation and 204 entered the ATRA randomisation. The arms were balanced with respect to age; sex; disease type; WBC and performance score.

Complete remission was seen in 1 of 92 (1%) patients in the HU arm and 15 of 94 (17%) in the LD Ara-C arm (P=0003). Overall survival was considerably improved (hazard ratio 0.61, 95% Cl 0.45 to 0.82, p=0.001). This improvement in outcome was not obtained at the expense of less well tolerated treatment: toxicity and supportive care requirements were similar between the two groups. However, there were no significant differences in outcome between patients given ATRA or not overall or within the treatment arms, although numbers were too small to rule out moderate benefits or disbenefits of treatment (hazard ratio for OS 0.97, 95% Cl 0.73 to 1.28, p=0.8).

We conclude that LD-Ara-C in the schedule chosen could be adopted as a standard of care for older patients not fit for intensive chemotherapy but the outcome remains poor. Future strategies could combine Low Dose Ara-C with novel agents. This trial received a research grant from the UK Leukaemia Research Fund.