PHASE-I AND CLINICAL PHARMACOLOGICAL EVALUATION OF 4'-DEOXYDOXORUBICIN IN PATIENTS WITH ADVANCED CANCER

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (4) , 1862-1868
Abstract
A Phase I and initial clinical pharmacological evaluation of 4''-deoxydoxorubicin (4''-DXDX) was conducted, administering the drug i.v. on an every 21-day schedule to 60 patients with advanced cancer. Patients were treated at 6 dosage levels ranging from 10 to 35 mg/m2. Leukopenia was the dose-limiting toxic effect, and no cardiac, renal or hepatic toxicity was observed; stomatitis was not seen; and there were no drug-related deaths. Significant alopecia was rare at doses less than 35 mg/m2, mild nausea and vomiting occurred in 1/3 of patients at myelosuppressive doses; 12 patients had a transient local urticarial reaction. In the 30 patients with measurable disease, 2 partial remissions were seen, lasting 5 mo. in a patient with a nasopharyngeal adenocarcinoma, and 7 mo. in a patient with endometrial adenocarcinoma. The recommended dose of 4''-DXDX for Phase II studies is 30 mg/m2 in good-risk patients and 25 mg/m2 in moderate-risk or heavily pretreated patients. Pharmacokinetic studies were carried out in 10 patients, 4 of whom received 4''-DXDX at a dose of 10 mg/m2 and 6 at 30 mg/m2. Disappearance of 4''-DXDX from plasma was triphasic with a rapid initial phase clearance showing a t1/2.alpha. of 1-2 min and a prolonged terminal phase with a median t1/2.gamma. in excess of 90 h in patients receiving 30 mg/m2.