[D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P inhibits the growth of human small cell lung cancer xenografts in vivo.

ABSTRACT

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.