Adjuvant treatment of operable stomach cancer with polyadenylic.polyuridylic acid in addition to chemotherapeutic agents: a preliminary report.

A randomized trial of polyadenylic.polyuridylic acid [poly(A).poly(U)] in addition to chemotherapy was undertaken in patients with stomach cancer following curative gastrectomy. They were randomized into a group of 108 patients receiving chemotherapy plus poly(A).poly(U) and a control group of 116 patients receiving chemotherapy alone. Chemotherapy consisted of injections of 5-fluorouracil, 12 mg/kg once weekly and adriamycin, 40 mg/m2 once every 3 weeks, continuously after operation. Poly(A).poly(U) was infused in a 100 mg dose, once a week six times from 5 days after the first injection of chemotherapeutic agents and 6 months later in a half dose similarly. At 55 months after initiation of the trial, the mean follow-up periods were 24 months for both groups. It has been revealed that patients who received the combined treatment postoperatively showed a lesser mortality and lower rate of recurrence, both reflecting significant increases in overall (P less than 0.05) and relapse-free (P less than 0.02) survivals as compared to those who received chemotherapy alone. This effect is more pronounced in patients having moderately advanced lymphnode involvement (N1) than in patients without (N0) or more advanced (N2) involvement. Thus, poly(A).poly(U) appears to be an effective agent when used postoperatively with chemotherapy in stomach cancers.

Adjuvant treatment of operable stomach cancer with polyadenylic.polyuridylic acid in addition to chemotherapeutic agents. Differential effect on natural killer cell and antibody-dependent cellular cytotoxicity.

Peripheral blood lymphocytes of operable stomach cancer patients were evaluated sequentially for their natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities before and after chemotherapy in association with polyadenylic.polyuridylic acid [poly(A).poly(U)]. Their cytotoxicity was measured by 4 h-chromium release assays, using human K562 and sensitized murine L1210 cells as targets for assays of NK and ADCC respectively. The mean NK cytotoxicity of 89 patients before treatment was significantly lower than that of the 18 sex- and age-matched healthy controls, whereas assays of ADCC showed similar levels of cytotoxicity in both groups. Patients who had received postoperative chemotherapy (5 fluorouracil, 12 mg/kg and adriamycin, 40 mg/M2) once, had, 5 days after injection, NK cytotoxicity levels similar to those before treatment. For these patients, an additional administration of poly(A).poly(U) (100 mg) resulted, 2 days later, in a significant increase in the levels of NK cytotoxicity without affecting the levels of ADCC. Repeated injections of poly(A).poly(U) alternated with chemotherapy induced, consistently, exclusive enhancement of NK activity after each injection. These results suggest that the effector cells for NK and ADCC activities are of functionally different cell populations.