Disposition of mitoxantrone in cancer patients

David S Alberts, Y. M. Peng, S. Leigh, Thomas P Davis, D. L. Woodward

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

We have used a highly sensitive high-performance liquid chromatographic assay to evaluate the pharmacokinetics and tissue disposition of mitoxantrone, an investigational anthracene derivative which has shown significant activity during Phase II clinical trials in the treatment of metastatic breast cancer, unfavorable histology non-Hodgkin's lymphoma, and acute leukemia. Mitoxantrone (12 mg/sq m over 30 to 35 min in 250 ml of dextrose 5% in water) and 14C-labeled mitoxantrone (specific activity, 8.85 μCi/mg) were administered to eight patients who had advanced soft tissue cancers. The plasma disappearance of mitoxantrone concentrations measured by high-performance liquid chromatography was best described by a three-compartment model with a mean t(α) of 0.1 h, a t(β) of 1.1 h, and a t(γ) of 42.6 h. The mean apparent V(c) was 12.2 liters/sq m, while the mean V(d) was 1875 liters/sq m. The mean plasma clearance was 0.57 liters/min/sq m, and the mean renal clearance was 45 ml/min/sq m. Only 6.5% of the total mitoxantrone dose was excreted in the urine as unchanged drug over 5 days. The mean recovery of 14C-labeled material in feces over 5 days was 18.3% of the administered dose. Thirty-five days after mitoxantrone administration to a patient who died of progressive kidney cancer, approximately 15% of the 14C dose could be accounted for in seven major organs. We conclude that mitoxantrone appears to distribute into a deep tissue compartment from which it is slowly released. These data provide a pharmacological rationale for use of mitoxantrone on an intermittent dosing schedule.

Original languageEnglish (US)
Pages (from-to)1879-1884
Number of pages6
JournalCancer Research
Volume45
Issue number4
StatePublished - 1985

Fingerprint

Mitoxantrone
Neoplasms
Phase II Clinical Trials
Kidney Neoplasms
Feces
Non-Hodgkin's Lymphoma
Histology
Appointments and Schedules
Leukemia
Pharmacokinetics
High Pressure Liquid Chromatography
Urine
Pharmacology
Breast Neoplasms
Kidney
Glucose
Water

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Alberts, D. S., Peng, Y. M., Leigh, S., Davis, T. P., & Woodward, D. L. (1985). Disposition of mitoxantrone in cancer patients. Cancer Research, 45(4), 1879-1884.

Disposition of mitoxantrone in cancer patients. / Alberts, David S; Peng, Y. M.; Leigh, S.; Davis, Thomas P; Woodward, D. L.

In: Cancer Research, Vol. 45, No. 4, 1985, p. 1879-1884.

Research output: Contribution to journalArticle

Alberts, DS, Peng, YM, Leigh, S, Davis, TP & Woodward, DL 1985, 'Disposition of mitoxantrone in cancer patients', Cancer Research, vol. 45, no. 4, pp. 1879-1884.
Alberts DS, Peng YM, Leigh S, Davis TP, Woodward DL. Disposition of mitoxantrone in cancer patients. Cancer Research. 1985;45(4):1879-1884.
Alberts, David S ; Peng, Y. M. ; Leigh, S. ; Davis, Thomas P ; Woodward, D. L. / Disposition of mitoxantrone in cancer patients. In: Cancer Research. 1985 ; Vol. 45, No. 4. pp. 1879-1884.
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