Pharmacokinetics of intraperitoneal hyperthermic perfusion with mitoxantrone in ovarian cancer

M. O. Nicoletto, R. Padrini, F. Galeotti, E. Ferrazzi, G. Cartei, F. Riddi, M. Palumbo, M. De Paoli, A. Corsini

Research output: Contribution to journalArticle

Abstract

Purpose: Theoretical data and experimental assumptions indicate that intraperitoneal hyperthermic chemotherapy may play a role in the treatment of peritoneal carcinomatosis. The feasibility, tolerability and pharmacokinetics of intraperitoneal hyperthermic perfusion with mitoxantrone were studied in patients with pretreated ovarian cancer. Methods: After cytoreductive surgery, 11 patients underwent intraperitoneal hyperthermic perfusion with mitoxantrone. A heated (4243 °C) solution of the drug (28 mg/m2) was recycled through a perfusion apparatus into the abdominal cavity for 90 min. Treatment was repeated every month for two to four cycles. In six patients blood and peritoneal perfusate samples were collected at 0.5, 1, 1.5, 2, 4, 8, 16 and 24 h after drug administration and mitoxantrone was assayed by an HPLC method. Results: Although treatment was generally well tolerated, all patients developed transient intestinal subocclusion. Maximal mitoxantrone plasma concentrations (C(max)), times to C(max) (T(peak)) and area under the curves (AUC) were highly variable between subjects (C(max) 14-337 ng/ml; T(peak) 0.5-8 h; AUC 222-4130 ng. ml-1 · h). The plasma to peritoneal fluid AUC ratio was significantly higher during the second (0.177) than during the first cycle (0.066), suggesting a cycle-dependent increase in systemic bioavailability. Furthermore, when comparing present data with those reported previously, hyperthermic perfusion may have lowered the mitoxantrone levels in the peritoneal fluid without greatly influencing plasma levels. Conclusions: Intraperitoneal mitoxantrone administered under hyperthermia to advanced ovarian cancer patients is feasible and well tolerated. Mitoxantrone pharmacokinetics may be altered by repeated intraperitoneal administration (increased bioavailability) and by hyperthermic perfusion (possibly, increased peritoneal tissue uptake).

Original languageEnglish
Pages (from-to)457-462
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume45
Issue number6
Publication statusPublished - 2000

Keywords

  • Hyperthermia
  • IPHP
  • Mitoxantrone
  • Ovarian cancer
  • Pharmacokinetics

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

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  • Cite this

    Nicoletto, M. O., Padrini, R., Galeotti, F., Ferrazzi, E., Cartei, G., Riddi, F., Palumbo, M., De Paoli, M., & Corsini, A. (2000). Pharmacokinetics of intraperitoneal hyperthermic perfusion with mitoxantrone in ovarian cancer. Cancer Chemotherapy and Pharmacology, 45(6), 457-462.