A phase I trial of dactinomycin intravenous infusion in patients with advanced malignancies

Eighteen patients with advanced malignancies refractory to other forms of treatment were given dactinomycin (Act D) as continuous intravenous infusions. Their median age was 51 years (range, 36-67); their median performance status was 50 (range, 40-90) on the Karnofsky scale. Act D was administered continuously for 5 days, utilizing a central venous line and a perfusion pump. The starting dose was 0.1 mg/m²/24 hours x 5 days (total dose, 0.5 mg/m²) and was escalated according to a modified Fibonacci scale to 0.2, 0.33, and 0.5 mg/m²/24 hours x 5 days, respectively. Three, three, four, and eight patients were entered, respectively, in each dose level. Toxicities observed were: leukopenia in four patients (nadir leukocyte count <1000 cells/mm³ in one patient and 2000-3000 cells/mm³ in 3 patients); thrombocytopenia, with nadir platelet counts between 50,000 and 100,000 platelets/mm³ in 2 patients; stomatitis in four patients; and nausea in three patients. Vomiting was not observed during the infusions. Two patients may have had a radiation recall phenomenon. Blood count depression, nausea, and mucositis were transient, resolving after a few days. One patient at level IV died of sepsis, which was diagnosed on the fourth day of the infusion, before leukopenia intervened. No objective responses were seen. It was concluded that a higher dose of Act D can be given by continuous infusion than by a bolus injection; the authors recommended 0.5 mg/m²/day x 5 days (total dose, 2.5 mg/m²) for further studies.