Rc. French et al., EFFECT OF HUMAN RECOMBINANT INTERFERON-CR ON THE ACTIVITY OF CIS-DIAMMINEDICHLOROPLATINUM(II) IN HUMAN NON-SMALL-CELL LUNG-CANCER XENOGRAFTS, Cancer investigation, 13(6), 1995, pp. 595-603
Interferons (IFNs) augment the effect of some antitumor agents, includ
ing cis-diamminedichloroplatinum(II) (cDDP), in experimental systems.
The effect of human recombinant interferon-alpha(2b) (rIFN alpha) on t
he cDDP-dependent growth delay of a human non-small cell lung cancer e
stablished as a xenograft in nude mice (NX002) has been investigated.
IFN (10(5) IU/mouse, s.c.) as a single agent had no effect on the grow
th of the xenograft. cDDP (4.2 mg/kg, i.p.) caused a specific growth d
elay of 0.42, and this delay was significantly enhanced (to 1.08) by c
oncomitant dosing with the otherwise inactive IFN, Possible mechanisms
for this supra-additive relationship between IFN and cDDP have been i
nvestigated: increased intratumoral accumulation of platinum was seen
at late time points (maximally at 36 hr) during the pharmacokinetic be
ta-phase cDDP elimination from the plasma of the nude mice. Tumor:plas
ma platinum concentration ratios at 36-48 hr indicated significantly i
ncreased accumulation of platinum in tumors from IFN-treated mice comp
ared to controls (p < 0.05). Scheduling experiments suggest that this
IFN-mediated effect can persist for 4 hr. These differences may accoun
t for the enhanced antitumor activity of cDDP when coadministered with
IFN.