Phase I and clinical pharmacological evaluation of 4'-deoxydoxorubicin in patients with advanced cancer Journal Article
| Authors: | Stanton, G. F.; Raymond, V.; Wittes, R. E.; Schulman, P.; Budman, D.; Baratz, R.; Williams, L.; Petroni, G. R.; Geller, N. L.; Hancock, C.; Kreis, W.; Young, C. W. |
| Article Title: | Phase I and clinical pharmacological evaluation of 4'-deoxydoxorubicin in patients with advanced cancer |
| Abstract: | We have conducted a Phase I and initial clinical pharmacological evaluation of 4'-deoxydoxorubicin (4'-DXDX), administering the drug i.v. on an every 21-day schedule to 60 patients with advanced cancer. Patients were treated at six dosage levels ranging from 10 to 35 mg/sq m. 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 closes less than 35 mg/sq m, mild nausea and vomiting occurred in one-third of patients at myelosuppressive doses; 12 patients had a transient local urticarial reaction. In the 30 patients with measurable disease, two partial remissions were seen, lasting 5 months in a patient with a nasopharyngeal adenocarcinoma, and 7 months in a patient with endometrial adenocarcinoma. The recommended dose of 4'-DXDX for Phase II studies is 30 mg/sq m in good-risk patients and 25 mg/sq m in moderate-risk or heavily pretreated patients. Pharmacokinetic studies were carried out in ten patients, four of whom received 4'-DXDX at a dose of 10 mg/sq m and six at 30 mg/sq m. Disappearance of 4'-DXDX from plasma was triphasic with a rapid initial phase clearance showing a f%« of 1 to 2 min and a prolonged terminal phase with a median f in excess of 90 h in patients receiving 30 mg/sq m. © 1985, American Association for Cancer Research. All rights reserved. |
| Keywords: | adult; cancer chemotherapy; aged; middle aged; unclassified drug; major clinical study; doxorubicin; skin toxicity; antineoplastic agents; endometrium carcinoma; endometrium cancer; neoplasms; leukopenia; nausea; vomiting; drug hypersensitivity; gastrointestinal toxicity; kinetics; drug distribution; drug clearance; nasopharynx carcinoma; drug blood level; phase 1 clinical trial; idarubicin; drug half life; drug therapy; alopecia; heart; adverse drug reaction; therapy; urticaria; intravenous drug administration; pharmacokinetics; pharynx cancer; diphenhydramine; pharynx; female genital system; nose cancer; drug evaluation; intoxication; cancer; humans; human; male; female; priority journal; article; esorubicin; blood and hemopoietic system; 13 hydroxyesorubicin; adriamycinone; doxorubicinol aglycone |
| Journal Title: | Cancer Research |
| Volume: | 45 |
| Issue: | 4 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1985-04-01 |
| Start Page: | 1862 |
| End Page: | 1868 |
| Language: | English |
| PUBMED: | 3978646 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 26 October 2021 -- Source: Scopus |
