A clinical phase I and pharmacokinetic study of BBR 2778, a novel anthracenedione analogue, administered intravenously, 3 weekly

• Published in: European journal of cancer (1990) 2000-12, Vol.36 (18), p.2353-2359
• Main Authors: Dawson, L.K., Jodrell, D.I., Bowman, A., Rye, R., Byrne, B., Bernareggi, A., Camboni, G., Smyth, J.F.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; BBR 2778; Biological and medical sciences; Chemotherapy; Dose-Response Relationship, Drug; Hematologic Diseases - chemically induced; Humans; Infusions, Intravenous; Isoquinolines - adverse effects; Isoquinolines - pharmacokinetics; Medical sciences; Middle Aged; Neoplasms - drug therapy; Neoplasms - metabolism; Pharmacokinetics; Pharmacology. Drug treatments; Phase I; Tomography, X-Ray Computed
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(00)00342-7

The anthracenedione analogue, BBR 2778 is an active antitumour agent preclinically and has reduced potential for cardiotoxicity compared with other similar drugs in preclinical models. BBR 2778 was administered 3 weekly by a 1 h intravenous (i.v.) infusion to 24 patients and the dose escalated rapidly from 20 to 240 mg/m 2. The dose-limiting toxicity (DLT) was neutropenia, common toxicity criteria (CTC) grade 4 in 3/5 patients at 240 mg/m 2. Other toxicities ⩾CTC grade 3 were: vomiting, lymphopenia, thrombocytopenia and lethargy. Blue discoloration of veins and urine was also noted. In 1 patient (120 mg/m 2, four cycles) left ventricular ejection reaction (LVEF) fell (CTC grade 2) but with no clinical sequelae. BBR 2778 plasma pharmacokinetics were biphasic (mean t 1/2β at 180 mg/m 2=14.1 h) and the urinary elimination of the unchanged drug was