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We determined the chemotherapeutic susceptibility of normal human granulocyte progenitor cells (CFU-C) and acute myelogenous leukemia cells (HL-60) in co-culture. Nucleated bone marrow cells and HL-60 cells were mixed in 0.3% agar containing McCoy's 5A medium, fetal bovine serum, human placenta-conditioned medium, and various concentrations of chemotherapeutic agents. They were incubated in 5% humidified CO2 at 37 degrees C for 8-10 days. CFU-C and HL-60 colonies were differentiated morphologically. The formation of CFU-C was progressively inhibited with the increasing number of HL-60 cells, whereas the presence or absence of bone marrow cells did not influence the number of HL-60 colonies. In separate culture, HL-60 cells were more sensitive to vincristine than were CFU-C cells. In co-culture, however, the CFU-C became more sensitive to vincristine than in the separate culture. Similarly, co-culture CFU-C were more sensitive to daunorubicin than in separate culture. These data indicate that HL-60 leukemic cells exert inhibitory effects on normal bone marrow CFU-C; in such an inhibited state, normal bone marrow is more susceptible to certain chemotherapeutic agents.

The clinical effects of combination chemotherapy with five or six anticancer drugs were investigated on the patients with the advanced cancer which originated mainly from the gastrointestinal tract.The five-drug regimen was found effective in 15 of 21 patients (71%) and the six-drug regimen in 29 of 43 patients (67%). The incidence of the cases which showed favorable clinical responses was higher in the five and six-drug regimens than in the one-, two-and three-drug regimens.Leukopenia, which occurred in almost half of the patients, was observed more frequently in cases of the six-drug regimen than in cases of the five-drug regimen. Gastrointestinal disturbances were found frequently during and after treatment, and seemed to be aggravated mainly by 5-FU and SP-G in these regimens. The main reasons for the discontinuation of these therapies were firstly leukopenia and secondly gastrointestinal upsets.The cases treated with the five or six-drug regimen survived only slightly longer than the non-treated.However, there were few remarkable differences in the survival period between the cases of the five or six-drug regimen and the cases of other regimens.