Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients

J Clin Oncol. 1996 Apr;14(4):1236-44. doi: 10.1200/JCO.1996.14.4.1236.

Abstract

Purpose: To conduct a phase I and pharmacologic study of the new topoisomerase I inhibitor, 9-aminocamptothecin (9-AC).

Patients and materials: A 72-hour infusion of 9-AC was administered every 14 days to 48 solid-tumor patients at doses of 5 to 59 microg/m2/h without granulocyte colony-stimulating factor (G-CSF) and 47 to 74 microg/m2/h with G-CSF.

Results: Without G-CSF, two of eight patients who received 47 microg/m2/h had dose-limiting neutropenia in their initial cycle, as did both patients who received 59 microg/m2/h (with a platelet count < 25,000/microL in one). With G-CSF, zero of seven patients treated with 47 microg/m2/h had dose-limiting neutropenia in their first cycle, while dose-limiting neutropenia occurred in six of 14 patients (with platelet count < 25,000/microL in five) entered at 59 microg/m2/h. Among 39 patients entered at > or = 25 microg/m2/h 9-AC with or without G-CSF, fatigue, diarrhea, and nausea/vomiting of grade 2 severity ultimately occurred in 54%, 30%, and 38%, respectively, while grade 3 toxicities of each type occurred in 8% of patients. Steady-state 9-AC lactone concentration (Css) increased linearly from 0.89 to 10.6 nmol/L, and correlated strongly with leukopenia ( r = .85).

Conclusion: The recommended phase II dose of 9-AC given by 72-hour infusion every 2 weeks is 35 microg/m2/h without G-CSF or 47 microg/m2/h with G-CSF support. Dose escalation in individual patients may be possible according to their tolerance.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacokinetics
  • Camptothecin / pharmacology
  • Drug Administration Schedule
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neutropenia / chemically induced
  • Neutropenia / therapy
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Granulocyte Colony-Stimulating Factor
  • 9-aminocamptothecin
  • Camptothecin