Timing of indomethacin in the control of prostaglandins, osteoclasts and bone destruction produced by VX2 carcinoma in rabbits.

Rabbits were injected with VX2 cancer cells into the left thigh or tibia, and given indomethacin 1-16 mg/kg daily starting on the day before tumour implantation or 7, 14 or 21 days after implantation. Indomethacin at 2 mg/kg and above from before tumour implantation reduced osteoclast proliferation and the amount of prostaglandin-like material extracted from homogenates of excised tumours, but the inhibition of bone destruction in vivo was significant only with indomethacin at 4 mg/kg and above. Indomethacin at 8 mg/kg reduced osteoclast proliferation and bone destruction, but the effect was statistically significant only when given within 7 days of inoculation with the tumour. The place of indomethacin and other inhibitors of prostaglandin synthesis has not yet been established in the management of patients with skeletal metastases. Drug administration might need to be started at the time of diagnosis and removal of the primary tumour, rather than when skeletal metastases are evident.