Linomide (N-phenylmethyl-1,2-dihydro-4-hydroxyl-1-methyl-2-oxo-quinoline-3- carboxamide) is a
quinoline 3-carboxamide which previously has been demonstrated to produce
immunomodulator and antitumor effects when given in vivo. To test the possible antitumor effects of
linomide against
prostatic cancers, rats bearing five distinct Dunning R-3327 rat
prostatic cancer sublines were treated daily with i.p.
injections of
linomide. These studies demonstrated that
linomide has a reproducible antitumor effect against all of the
prostatic cancers tested regardless of their growth rate, degree of morphologic differentiation, metastatic ability, or
androgen responsiveness. This antitumor effect is observed only in vivo, not in vitro, and involves a cytotoxic response of the
prostatic cancer cells. This cytotoxic response results in the retardation of the growth rate (i.e., increased
tumor volume doubling time) of primary
prostatic cancers and in metastatic lesions.
Linomide's growth retardation is reversible, and thus continuous daily treatment with
linomide is required for maximal antitumor response. Pretreatment of rats with
linomide before
tumor inoculation has no effect in addition to that produced by initiating
linomide treatment at the time of
tumor inoculation. No enhancement of either natural killer cell number or natural killer cell cytotoxic activity is induced by
linomide treatment in the
tumor-bearing rats. In addition, depletion of natural killer cell activity via
injections of asialo-GM1 antiserum does not prevent the antitumor effects of
linomide in vivo. Likewise, the antitumor effects of
linomide are also produced in
prostatic cancer-bearing athymic nude rats. These results suggest that the requirement for host involvement in the antitumor effects of
linomide against rat
prostatic cancers may involve both immune and nonimmune host mechanism(s) (e.g., antiangiogenesis).