Lk. Webster et al., A pharmacokinetic and phase II study of gallium nitrate in patients with non-small cell lung cancer, CANC CHEMOT, 45(1), 2000, pp. 55-58
This study investigated the pharmacokinetics and activity of gallium nitrat
e in non-small cell lung cancer when 700 mg/m(2) was given as a 30-min infu
sion with prehydration every 2 weeks. Gallium was measured in plasma and ur
ine using flameless atomic absorption spectrophotometry, and pharmacokineti
cs of total and ultrafilterable gallium were calculated. Twenty-five patien
ts with non-small cell lung cancer received 1-12 (median 2) courses of gall
ium nitrate every 2 weeks. Of 21 patients evaluable for response, 1 partial
response was recorded, 4 patients had stable disease, and 16 had progresse
d. The most serious toxicities were renal impairment and optic neuritis. Hy
pocalcaemia was recorded in 3 patients. The mean C-max was 15.2 +/- 3.1 mu
g/ml (range 9.5-21.2). Most gallium remained ultrafilterable for the first
10 h, after which plasma protein binding increased, and at 48 h only 11% wa
s present as ultrafilterable gallium. The elimination profiles of both tota
l and ultrafilterable gallium were biphasic, and the distribution phase con
sisted of ultrafilterable gallium, with a distribution half-life of 1.4 h.
Total gallium plateaued at 1.9 mu g/ml at between 8 and 12 h, and the estim
ated elimination half-life was 63 h. The elimination half-life of ultrafilt
erable gallium was 16.5 h. Inter- and intra-patient variability in pharmaco
kinetics was minimal. A mean of 50 +/- 14% of the gallium dose was excreted
in the urine within 48 h. A short infusion of gallium nitrate achieving hi
gh peak plasma concentrations results in little efficacy in non-small cell
lung cancer.