The antitumor activity of
doxorubicin and three new derivatives modified on the position 4' of the
amino sugar was tested against five human colon
tumors and two human
rectal tumors (originating from different patients) and xenografted into nude mice. The drugs tested were:
4'-epidoxorubicin; 4'-deoxydoxorubicin; and
4'-O-methyldoxorubicin. Mice were treated i.v. on a weekly basis for 3 to 4 weeks, starting when the
tumors were well established (advanced stage of
tumor treatment). No statistically significant effect was observed against the
tumors tested with the drugs
doxorubicin and
4'-epidoxorubicin.
4'-Deoxydoxorubicin was active against all the colon
tumors tested (4 of 5 statistically significant), and 4'-O-methuldoxorubicin was active against 4 of 5 colon
tumors tested (statistically significant). Overall, the activity of 5'-O-methyldoxorubicin was less than that of
4'-deoxydoxorubicin against the colon
carcinomas tested. Neither analog was active against the two rectal
carcinomas tested. The results of these studies indicate that: (a) the modifications in the chemical structure of
doxorubicin can alter the
biological properties and thus create new drugs varying in activity against different human
tumors; (b) the two antracycline derivatives,
4'-deoxydoxorubicin and
4'-O-methyldoxorubicin, appear to be good candidates for clinical trial against colon
carcinoma; and (c) the nude mice system can offer a great potential for identification of new
anthracycline analogs and, in general, new
anticancer agents of clinical interest.