A pilot phase I trial of continuous hyperthermic peritoneal perfusion with high-dose carboplatin as primary treatment of patients with small-volume residual ovarian cancer |
| |
| Authors: | Michael A Steller Merrill J Egorin Edward L Trimble David L Bartlett Eleanor G Zuhowski H Richard Alexander Robert L Dedrick |
| |
| Institution: | (1) Section of Gynecologic Oncology, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, US;(2) Office of Research Services, National Inst. of Health, Bethesda, MD 20892, USA, US;(3) Greenebaum Cancer Center and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA, TP;(4) Women and Infants Hospital, Women's Oncology, 1 Blackstone Place, 3rd Floor, Providence, Rhode Island 02905, USA e-mail: msteller@wihri.org, Tel.: +1-401-453-7520, Fax: +1-401-453-7529, IS |
| |
| Abstract: | Purpose: Because intraperitoneal (i.p.) therapy may provide a therapeutic advantage and because hyperthermia enhances carboplatin
(CBDCA) cytotoxicity, we evaluated the feasibility, toxicity, and pharmacokinetics of CBDCA given via continuous hyperthermic
peritoneal perfusion (CHPP) in patients with small-volume residual ovarian cancer. Patients and Methods: Six patients underwent optimal cytoreductive procedures (residual disease ≤5 mm) as initial treatment of stages II and III
epithelial ovarian adenocarcinoma. All patients received a 90-min CHPP at a CBDCA dose of 800–1200 mg/m2, with the perfusate being recirculated rapidly from a reservoir through a heat exchanger, resulting in i.p. temperatures
of 41–43 °C. Plasma, perfusate, and urine samples were collected and platinum was quantified by flameless atomic absorption
spectrophotometry. Results: At no time did any patient's core temperature exceed 40 °C. Peak perfusate platinum concentrations were 8- to 15-fold higher
than peak ultrafilterable plasma concentrations. The permeability-area product was extremely high and variable (14–90 ml/min),
resulting in a regional advantage of 1.9–5.3. The percentage of the dose absorbed ranged widely from 27% to 77%. Dose-limiting
hematologic toxicity was observed at a dose of 1200 mg/m2 and this was associated with a CBDCA AUC in plasma of 11 mg min ml−1. Conclusions: CHPP with CBDCA was safely given to three patients at a dose of 800 mg/m2, and dose-limiting hematologic toxicities observed at 1200 mg/m2, correlated with the plasma CBDCA exposure established when lower doses of CBDCA are given systemically. The pharmacokinetic
data are consistent with the expected effect of vigorous mixing on the exposed peritoneal surface area. Variable drug absorption
and clearance make the prediction of systemic exposure highly uncertain. These findings may have important implications for
novel therapies given i.p.
Received: 9 March 1998 / Accepted: 11 June 1998 |
| |
| Keywords: | Continuous hyperthermic peritoneal perfusion High-dose CBDCA Small-volume residual ovarian cancer Systemic exposure Hepatic toxicity |
| 本文献已被 SpringerLink 等数据库收录！ |
|
