[D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P inhibits the growth of human small cell lung cancer xenografts in vivo.
We report the effect of substance P analogue, [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P (D-Phe5SP), on the growth of human small cell lung cancer (SCLC) xenografts HC12 and ICR-SC112. Daily intraperitoneal (ip) administration (500 micrograms/day for 3 weeks) had no effect on HC12 growth rate. When administered by continuous 14-day subcutaneous (sc) infusion by osmotic minipump implanted adjacent to the tumour, D-Phe5SP 2.1 micrograms/day, caused significant inhibition (P < 0.05) of the growth of HC12 and ICR-SC112 on day 7 and day 14 compared with phosphate buffered saline (PBS)-treated controls. HC12 and ICR-SC112 tumour volume remained at 53-67% of control for 14-21 days postinfusion. D-Phe5SP 1 mg/day did not inhibit tumour growth, but dense fibrous capsules developed at the minipump outlet. Animals treated by sc infusion (but not ip) of PBS or D-Phe5SP failed to gain weight, and some groups lost weight. D-Phe5SP-treated animals had lower white blood counts than controls (not significant). These data suggest a potential clinical role for D-Phe5SP in the treatment of SCLC.
Everard
M J
MJ
Section of Medicine, Royal Marsden Hospital, Belmont, Surrey, U.K.
Macaulay
V M
VM
Millar
J L
JL
Smith
I E
IE
D000818:Animals; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D006131:Growth Inhibitors / Q000627:therapeutic use; D006801:Humans; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D014183:Transplantation, Heterologous
D006131:Growth Inhibitors; D011994:Recombinant Proteins; D013373:Substance P; C050702:substance P, Arg(1)-Pro(2)-Trp(7,9)-Leu(11)-