Phase I study of high-dose piroxantrone with granulocyte colony-stimulating factor

J Clin Oncol. 1993 Sep;11(9):1795-803. doi: 10.1200/JCO.1993.11.9.1795.

Abstract

Purpose: We performed a phase I trial of piroxantrone with and without granulocyte colony-stimulating factor (G-CSF) to determine whether the use of this cytokine would enable us to increase the dose-intensity of piroxantrone.

Patients and methods: Thirty-eight patients received 121 courses of piroxantrone administered once every 21 days. Initial patient cohorts received piroxantrone alone starting at 150 mg/m2 and the dose was escalated in subsequent patients until dose-limiting toxicity (DLT) was reached. Patient cohorts then received escalating doses of piroxantrone starting at 185 mg/m2 administered with G-CSF beginning day 2.

Results: Dose-limiting neutropenia occurred in three of six patients treated with 185 mg/m2 piroxantrone; the maximum-tolerated dose (MTD) of piroxantrone alone was 150 mg/m2. Three of six patients treated with piroxantrone and G-CSF exhibited dose-limiting thrombocytopenia at 445 mg/m2; the MTD of piroxantrone with G-CSF was thus 355 mg/m2. Seven patients developed symptomatic congestive heart failure (CHF) at cumulative piroxantrone doses ranging from 855 to 2,475 mg/m2 and two have died of cardiotoxicity. Of these patients, six of seven had previously received doxorubicin. Other nonhematologic toxicity was mild.

Conclusion: The use of G-CSF results in a more than twofold increase in the MTD of piroxantrone. However, symptomatic cardiotoxicity is prominent, especially in patients who have received prior treatment with anthracyclines.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Anthraquinones / administration & dosage*
  • Anthraquinones / adverse effects
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Bone Marrow Diseases / chemically induced
  • Bone Marrow Diseases / prevention & control
  • Drug Administration Schedule
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms / drug therapy*
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects

Substances

  • Anthraquinones
  • Antineoplastic Agents
  • Pyrazoles
  • Granulocyte Colony-Stimulating Factor
  • piroxantrone