MAG-CPT (camptothecin linked to a water-soluble polymeric backbone methacryloylglycynamide) was administered as a 30-minute infusion once every 4 weeks to patients with advanced solid malignancies. The starting dose was 30 mg/m^2. In total, 23 patients received 47 courses at six dose levels, with a maximum dose of 240 mg/m^2. Dose-limiting toxicities were myelosuppression, neutropenic sepsis, and diarrhea. One patient died after cycle 1 MAG-CPT at the maximum dose. The maximum tolerated dose and dose recommended for further clinical study was 200 mg/m^2.

Human HL-60, MOLT-4, and L-1210 cells were maintained in RPMI-1640 medium supplemented with 10% fetal calf serum, 100 U/mL penicillin, 100 micro-g/mL streptomycin, and 2 mM L-glutamine. All experiments were conducted during the exponential growth phase. To synchronize cells, exponentially growing cultures containing 6 x 10^5 cells per 1 mL were treated with 1 micro-g/mL of aphidicolin for 15 hours; resulting in 80% of the cells in the S-phase. Camptothecin was prepared in dimethyl sulfoxide and diluted in RPMI-1640 to the desired concentrations. Cellular DNA and protein content were measured by flow cytometry and cell viability was assayed by the PI exclusion test. The addition of camptothecin to cultures of myelogenous leukemic cells resulted in rapid (2-6 hours) restructuring of the cell cycle distribution, with a disappearance of S and G2 phase cells and increasing the proportion of G1 cells. Cytotoxic effects of camptothecin were observed at 0.02 micro-g/mL and higher.