4,6-Benzylidene-d1-D-glucose,
P-1013, a deuterated
benzaldehyde derivative which acts as a reversible
protein synthesis inhibitor in vitro, was evaluated for antitumor effects in two human
tumor xenografts implanced s.c. in nude mice. The
drug, dissolved in isotonic saline, was given p.o. daily for several weeks. For evaluation of
drug efficacy, mean
tumor volume growth curves were generated and
tumor volume doubling time (TD) as well as per cent change in
tumor size for the treated
tumors compared to control (T/C) were calculated.
P-1013 at 90 mg/kg for 49 days was effective against SK-OV-3 human ovarian
carcinoma (T/C 47% at day 40 and 50% increase in TD).
P-1013 at 90 mg/kg also suppressed growth of PANC-1 human
pancreatic carcinoma in two experiments (T/C 44 and 50%, 20 and 40% increase in TD, respectively). There was no indication of systemic toxicity in mice receiving
P-1013. Histological examinations of each
tumor showed that
P-1013 treatment of pancreatic xenografts reduced
tumor volume without inducing greater
necrosis than that comparable to respective control
tumors. For the ovarian xenograft, the histological examination indicated a higher fraction of
tumors with more than 50% necrotic tissue in two of the P-1013-treated groups compared with the control group (Fisher exact test, p = 0.12). It is possible that
P-1013, in addition to inhibiting the rate of
tumor volume growth, also induces
tumor necrotization in the ovarian xenograft.