Twelve patients with neoplasia undergoing therapy with 5-Buorouracil (5-FU) were immunized with Escherichiu coli Vi antigen a n d tetanus toxoid to test the primary and secondary humoral immune responses. Skin sensitization was attempted with 2,4-dinitrochlorobenzene, and a battery of common microbial skin tests were applied during and after therapy. Eight of 10 patients failed t o demonstrate a primary response. The responders made only mercaptoethanol-sensitive, presumably IgRI, antibody. The secondary response was completely inhibited in 4 of 9 patients a n d delayed until 10 days after cessation of drug in the others. Five of 6 patients tested failed to achieve hypersensitivity to DNCB. T h r e e of 6 patients showed reversion t o positive of one or more skin tests after therapy. This last somewhat unexpected finding may have reflected weakened skin reactivity in these patients with very limited life expectancy. In contrast to its variable effectiveness in rodents, 5-FU was confirmed to be a potent immunosuppressive agent in man.
MONG T H E CANCER CHEMOTHERAPEUTIC
A agents in current use, the pyrimidine analogs are perhaps the most variable in their immunosuppressive properties. While bromodeoxyuridine (BUdR) and cytosine arabinoside (ara-C) are potent immunosuppressive agents in several animal specie& 5 + 1 0 * 16 and in man,l6 iododeoxyuridine (IUdR) is ineffective in all species thus far tested.5. 10 5-fluorouracil (5-FU) is ineffective in the rabbit,24 weakly active in the mouse,1* but probably effective in man.20 Since the results of Santos et aL20 indicated that 5-FU and 5-fluoro-2'deoxyuridine (5-FUdR) suppressed antibody synthesis, we decided to investigate systematically the immunosuppressive properties of 5-FU in the nontoxic dosage schedules currently used by our group in treating solid tumors. These studies indicate that 5-FU in these schedules is a strong suppressant of pri-From the Departments of Medicine and Phannacol-