Phase I clinical trial of mitoxantrone: A new anthracenedione anticancer drug

Abstract

Mitoxantrone, 1,4-dihydroxy-5,8-bis(((2-[(2-hydroxyethyl)amino]ethyl) amino))-9,10-anthracenedione dihydrochloride, a new antitumor agent was evaluated in nine cancer patients as part of a phase I trial. In general, the drug was well tolerated. Leukopenia was the dose-limiting toxic effect. Mild to moderate leukopenia (but not neutropenia or thrombocytopenia) occurred in four of six patients given 4 mg/m2/week after a mean of 2.75 doses (range, 2-4 doses) and in all three patients given 5 mg/m2/week after three doses. Only one patient had mild nausea and vomiting. No patient experienced alopecia or mucositis, and none showed evidence of any cardiac, renal, hepatic, or pulmonary abnormality. Mitoxantrone treatment induced two partial remissions (patients with metastatic squamous cell carcinomas of the hypopharynx and rectum) and one mixed response (patient with gastric carcinoma). For phase II studies the starting dose, when used on a weekly schedule, should be 5 mg/m2 in patients who are known to have adequate bone marrow reserve.

Different mechanisms of decreased drug accumulation in doxorubicin and mitoxantrone resistant variants of the MCF7 human breast cancer cell line

“…In addition, DOX is an integral component of many combination chemotherapy regimens for breast cancer. Mitoxantrone (Mitox) belongs to a new class of synthetic chemotherapeutic agents, the anthracenediones (Alberts et al, 1980). Numerous comparisons have been made between DOX and Mitox in that both compounds possess dihydroxyquinones and are believed to intercalate DNA (Shenkenberg & Von Hoff, 1986).…”

Surgical Resection and Intraperitoneal Chemotherapy for Recurrent Abdominal Sarcomas

“…In addition, it has little vesicant effects and minimal systemic absorption when given intraperitoneally, thus enabling maximum in vivo drug concentration at the location of disease. 22,23 Mitoxantrone possesses a distinctive blue color, which was of additional benefit. All peritoneal surfaces in contact with mitoxantrone were stained blue and remained blue for up to 2 years after the last treatment.…”

“…21 It binds DNA and induces both protein-and non-protein-associated DNA strand scissions. 22,23 Mitoxantrone was selected for this study for several reasons. It is an anthracycline derivative and thus a member of a family of drugs with proven effectiveness against sarcomas.…”

Quantitative Online Detection of Low‐Concentrated Drugs via a SERS Microfluidic System

“…[31][32][33] The molecular structure of this drug is shown in Figure 1 B. Due to resonance effects Raman spectroscopy is a powerful tool for the investigation of mitoxantrone.…”