Phase I/II trial and pharmacokinetics of intrathecal diaziquone in refractory meningeal malignancies.

Abstract

PURPOSE:

Because there is a compelling need to develop new agents for intrathecal use, we investigated the safety, efficacy, and CSF pharmacokinetics of diaziquone (AZQ) following intrathecal administration in patients with refractory meningeal malignancies.

PATIENTS AND METHODS:

Thirty-nine patients received 45 courses of intrathecal AZQ. Two schedules were studied; twice-weekly administration of a 1- or 2-mg dose and "concentration times time" (C x T) administration of 0.5 mg every 6 hours for three doses, administered once weekly.

RESULTS:

Dose-limiting toxicity consisting of headache, nausea, or vomiting occurred in only three patients and only at the 2-mg, twice weekly dose. The schedules of 1 mg twice-weekly and 0.5 mg every 6 hours for three doses were well tolerated. Thirty-seven courses were assessable for response. The overall response rate was 62%. Complete responses (CRs) occurred in 14 of 37 courses (38%) and partial responses (PRs) occurred in nine of 37 courses (24%). Among patients with meningeal leukemia, CRs were observed in 11 of 26 courses (42%) and PRs in nine of 26 courses (35%). There was no difference in response rate related to dose or schedule. The pharmacokinetic behavior of intrathecally administered AZQ was characterized by biexponential disappearance from ventricular CSF, with mean half-lives of 18.2 and 78.6 minutes. The mean clearance rate was 0.37 mL/min.

CONCLUSION:

Intrathecal AZQ is safe, well tolerated, and highly active against refractory meningeal malignancies.

• Authors: S L Berg, F M Balis, S Zimm, R F Murphy, J Holcenberg, J Sato, G Reaman, P Steinherz, A Gillespie, K Doherty
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 10 Issue 1 Pg. 143-8 (Jan 1992) ISSN: 0732-183X [Print] United States
• PMID: 1727916 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antineoplastic Agents
• Aziridines
• Benzoquinones
• diaziquone

Topics

• Adolescent
• Adult
• Antineoplastic Agents (pharmacokinetics, therapeutic use)
• Aziridines (pharmacokinetics, therapeutic use)
• Benzoquinones (pharmacokinetics, therapeutic use)
• Child
• Child, Preschool
• Drug Administration Schedule
• Drug Evaluation
• Female
• Humans
• Injections, Spinal
• Male
• Meningeal Neoplasms (drug therapy, secondary)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)