SEVERE HEPATIC TOXICITY AFTER TREATMENT WITH VINCRISTINE AND DACTINOMYCIN USING SINGLE-DOSE OR DIVIDED-DOSE SCHEDULES - A REPORT FROM THE NATIONAL WILMS-TUMOR STUDY

To evaluate the effect of dactinomycin (AMD) dose and schedule on the frequency of severe hepatic toxicity in unirradiated National Wilms' Tumor Study-4 (NWTS-4) patients, we reviewed the records of 154 children randomized to single-dose AMD and 176 children randomized to divided-dose AMD administration. All the children also received vincristine in identical dose schedules for the first 10 weeks. The frequency of severe hepatic toxiciry encountered in the early weeks of therapy was 14.3% (five of 35) among patients treated with 60 μg/kg of AMD, 3.7% (four of 108) among patients given 45 μ/kg, and 2.8% (five of 176) among patients treated with 15 μ9/kg per dose times five doses (P = .025). The data suggest an increased frequency of severe hepatic toxicity with the higher, single-dose schedule of administration. However, the frequency of severe hepatic toxicity among the patients in the two remaining groups is markedly higher than the 0.4% observed among similar unirradiated patients in NWTS-3. The relationship of this toxicity to factors such as anesthetic agents, blood transfusions, intercurrent viral infection, or other presently unrecognized causes can be further evaluated only with a detailed investigation such as a casecontrol study. © 1990 by American Soci-ety of Clinical Oncology.