PRECLINICAL EVALUATION OF LU-79553 - A NOVEL BIS-NAPHTHALIMIDE WITH POTENT ANTITUMOR-ACTIVITY

LU 79553 is a novel bis-naphthalimide which is highly cytotoxic in vit ro with EC(50) (concentration required for 50% inhibition of growth) r anging from 2 x 10(-7) to 5 x 10(-10) hr. A number of studies were con ducted to examine its antitumor activity in human xenograft models. In addition, we wanted to explore the possible schedule dependency of LU 79553 cytotoxicity in these xenograft models. Complete regression of MX-1 (mammary carcinoma) xenografts was observed when LU 79553 was adm inistered i.v. daily for 5 doses at 20 mg/kg (2 cycles starting on Day s 6 and 20) or every 3 days for 2 doses at 55 mg/kg (2 cycles starting on Days 6 and 13) or every 7 days for 4 doses. Complete regression wa s also seen in the MX-1 model when tumors were staged at 1-2 g prior t o the initiation of treatment. Regressions (complete or partial) were observed in the LX-1 (lung), CX-1 (colon), DLD (colon), and LOX (melan oma) xenograft models. A significant increase in the median survival t ime of OVCAR-3- (ovarian carcinoma) bearing mice was noted in LU 79553 -treated animals (treated/control = 195%). The excellent activity of t his compound in such a wide variety of tumor types suggests LU 79553 m erits further investigation in clinical trials.