EFFECTS OF LINOMIDE ON ADVANCED PROSTATE-SEMINAL VESICLE CANCERS IN LOBUND-WISTAR RATS

BACKGROUND. Angiogenesis and antiangiogenesis, as applied to oncology, are phenomena in which (1) tumors acquire a new blood vascular system from the host that is needed for their growth progression and metasta sis; and (2) factors are produced that interfere with neovascularizati on, thereby inhibiting growth and metastasis of the tumor. Linomide, a chemical antiangiogenesis agent, inhibited the growth of transplanted tumors in mice and rats and inhibited the early development of metast asizing tumors induced in the prostate-seminal vesicle (P-SV) complex of genetically susceptible Lobund-Wistar (L-W) rats. METHODS. L-W rats with small induced P-SV tumors were treated with a recommended dosage of linomide (100 mg/kg BW/day) by the intraperitoneal and oral routes . The rats were monitored for the next 1-2 months, and the primary and metastatic tumors were compared with related data in drug-free tumor- bearing control rats. RESULTS. P-SV tumors in linomide-treated and unt reated control rats continued to grow, except that in the former (1) t he tumors were marginally smaller, (2) the centers of the primary P-SV tumors had failed to grow, (3) the peripheral areas of the tumors con tained actively proliferating tumor cells, and (4) metastatic P-SV tum ors in the lungs were disrupted with focal areas of necrosis, but area s of intact tumor cells survived. Spread of tumor cells into the perit oneal cavity was not inhibited. Rats on orally administered linomide l ived significantly longer than rats inoculated by the intraperitoneal route and untreated control rats. The dosage of Linomide used showed e vidence of toxicity. CONCLUSIONS. Although primary and metastatic P-SV tumors were damaged in L-W rats treated with linomide, this antiangio genic drug was of minimal therapeutic benefit to rats in which a palpa ble P-SV tumor had developed before onset of treatments. (C) 1998 Wile y-Liss, Inc.