Tallysomycin S10b--a phase I trial

Tallysomycin S10b is a new bleomycin analogue. In animal studies it has shown the same degree of antineoplastic activity as bleomycin; however in contrast to that of bleomycin, its dose-limiting effect in animal systems is renal toxicity and its pulmonary toxicity is less pronounced. A total of 16 patients received tallysomycin S10b at three exploratory levels: 3 patients were given a dose of 1.25 mg/m2, 9 received 2.5 mg/m2 and 4 were given 5 mg/m2 as i.v. bolus injections twice weekly. Before treatment and every 3 weeks, plain chest X-rays, pulmonary function tests, renography and 51Cr-EDTA clearance were carried out. No renal toxicity was found in any of the treatment groups. In the first two groups no changes in chest X-rays were observed during treatment, whereas in the third group a decrease in single-breath carbon monoxide diffusion capacity (DLCO) was seen in one patient until the treatment was discontinued. Two of four patients receiving 5 mg/m2 developed interstitial pneumonitis at total doses of 104 and 160 mg, respectively. During the trial no haematologic or hepatic changes occurred due to the drug. The frequency of occurrence of skin changes, stomatitis and fever increased with the cumulative dose of tallysomycin S10b, and these side effects were similar to those seen with bleomycin. No tumor regression was seen during the trial. In contrast to the findings in previous animal studies, we found that the dose-limiting effect was pulmonary and not renal toxicity. The recommended dose for further phase II trials is 2.5 mg/m2 twice weekly, with careful monitoring of the pulmonary function.