Doxorubicin-DNA complex: a phase I clinical trial.
Thirty-five patients with advanced malignancies were treated with doxorubicin-DNA complex in a phase I clinical trial. The patients ranged in age from 30 to 77 years (median, 51) and received doxorubicin-DNA in doses that ranged from 20 to 135 mg/m2. Of the doses administered, 73% were 60-90 mg/m2 (median, 60). Nonhematologic toxic effects included nausea and vomiting in 32% of the patients, fever and chills in 24% mucositis in 18%, and decreases in ECG QRS voltage of greater than 30% in 18%. Fever of unknown origin was seen in 26% of the patients, with documented infection in 9%; 6% had drug-related deaths. All patients experienced alopecia. Hematologic toxic effects (median day, Day 14) included median granulocyte count nadirs of 0.8 X 10(3)/microliter at a 60-mg/m2 dose and 0.3 X 10(3)/microliter at 75 mg/m2. Thrombocytopenia was less severe, with median nadir counts of 131,000 cells/microliter at a 60-mg/m2 dose on median day. Day 13. Treatment courses could be repeated every 3 weeks. Clinical responses (complete plus partial) were seen in 12% of the patients, with an additional 48% showing stable disease. No patients entered in the study were known to be doxorubicin-resistant. Based on these data, we recommend a starting dose of 60 mg/m2 in patients with adequate bone marrow reserve and 50 mg/m2 in those with compromised bone marrows. Doxorubicin-DNA exhibits major clinical toxic effects on the gastrointestinal and hematopoietic systems, with dose-limiting granulocytopenia.
D000328:Adult; D000368:Aged; D004247:DNA / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005069:Evaluation Studies as Topic; D005260:Female; D006413:Hematopoietic System / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
D004317:Doxorubicin; D004247:DNA