Effect of human recombinant interferon-alpha on the activity of cis-diamminedichloroplatinum(II) in human non-small cell lung cancer xenografts.
Interferons (IFNs) augment the effect of some antitumor agents, including cis-diamminedichloroplatinum(II) (cDDP), in experimental systems. The effect of human recombinant interferon-alpha 2b (rIFN alpha) on the cDDP-dependent growth delay of a human non-small cell lung cancer established 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 growth of the xenograft. cDDP (4.2 mg/kg, i.p.) caused a specific growth delay of 0.42, and this delay was significantly enhanced (to 1.08) by concomitant dosing with the otherwise inactive IFN. Possible mechanisms for this supra-additive relationship between IFN and cDDP have been investigated: increased intratumoral accumulation of platinum was seen at late time points (maximally at 36 hr) during the pharmacokinetic beta-phase of cDDP elimination from the plasma of the nude mice. Tumor:plasma platinum concentration ratios at 36-48 hr indicated significantly increased accumulation of platinum in tumors from IFN-treated mice compared to controls (p < 0.05). Scheduling experiments suggest that this IFN-mediated effect can persist for 4 hr. These differences may account for the enhanced antitumor activity of cDDP when coadministered with IFN.
French
R C
RC
Medical Oncology Unit Western General Hospital, Edinburgh, Scotland.
Bowman
A
A
MacLeod
K G
KG
Ritchie
A A
AA
Cummings
J
J
Smyth
J F
JF
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins; D014183:Transplantation, Heterologous
D007370:Interferon Type I; D011994:Recombinant Proteins; D002945:Cisplatin