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

Eur J Cancer. 2000 Dec;36(18):2353-9. doi: 10.1016/s0959-8049(00)00342-7.

Abstract

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/m2. The dose-limiting toxicity (DLT) was neutropenia, common toxicity criteria (CTC) grade 4 in 3/5 patients at 240 mg/m2. Other toxicities > or = CTC grade 3 were: vomiting, lymphopenia, thrombocytopenia and lethargy. Blue discoloration of veins and urine was also noted. In 1 patient (120 mg/m2, four cycles) left ventricular ejection reaction (LVEF) fell (CTC grade 2) but with no clinical sequelae. BBR 2778 plasma pharmacokinetics were biphasic (mean t(1/2) at 180 mg/m2 = 14.1 h) and the urinary elimination of the unchanged drug was < 10%. In a patient with previously treated small cell lung carcinoma (SCLC), a 49% reduction in measurable disease was noted with resolution of pericardial and pleural effusions (120 mg/m2 x eight cycles). From the results of this phase I study a dose of 180 mg/m2 as a 1 h infusion every 3 weeks would be recommended for phase II trials.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Hematologic Diseases / chemically induced
  • Humans
  • Infusions, Intravenous
  • Isoquinolines / adverse effects
  • Isoquinolines / pharmacokinetics*
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Tomography, X-Ray Computed

Substances

  • Antineoplastic Agents
  • Isoquinolines
  • pixantrone