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 metastasis; and (2) factors are produced that interfere with neovascularization, 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 metastasizing 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 untreated control rats continued to grow, except that in the former (1) the tumors were marginally smaller, (2) the centers of the primary P-SV tumors had failed to grow, (3) the peripheral areas of the tumors contained actively proliferating tumor cells, and (4) metastatic P-SV tumors in the lungs were disrupted with focal areas of necrosis, but areas of intact tumor cells survived. Spread of tumor cells into the peritoneal cavity was not inhibited. Rats on orally administered linomide lived significantly longer than rats inoculated by the intraperitoneal route and untreated control rats. The dosage of linomide used showed evidence of toxicity. CONCLUSIONS Although primary and metastatic P-SV tumors were damaged in L-W rats treated with linomide, this antiangiogenic drug was of minimal therapeutic benefit to rats in which a palpable P-SV tumor had developed before onset of treatments. Prostate 35:43–49, 1998. © 1998 Wiley-Liss, Inc.