A comparison of hetastarch and peritoneal dialysis solution for intraperitoneal chemotherapy delivery.
OBJECTIVE
Intraperitoneal chemotherapy administration results in high drug concentration locally with low systemic toxicity. We compared the pharmacokinetics of paclitaxel infused intraperitoneally in two isotonic carrier solutions, 1.5% dextrose peritoneal dialysis solution (peritoneal dialysis solution) and hetastarch (6% hydroxyethyl starch), a high molecular weight solution.


METHODS
Twenty patients with peritoneal carcinomatosis were randomized into one of two groups to receive early postoperative intraperitoneal chemotherapy with paclitaxel for 5 consecutive days following cytoreductive surgery. One group (8 patients) received paclitaxel in one litre of peritoneal dialysis solution; the other group (12 patients) received paclitaxel in one litre of hetastarch. Samples of peritoneal fluid and venous blood were taken during the 23 h dwell time. Volumes of chemotherapy solution were recorded and concentrations of paclitaxel determined by high performance liquid chromatography.


RESULTS
Hetastarch clearance from the peritoneal cavity was reduced when compared to peritoneal dialysis solution. The mean volume of fluid remaining in the peritoneal cavity at 23 h was 900 ml +/-373.7 (SD) with hetastarch, and 285 ml (+/-157.5) with peritoneal dialysis solution (P=0.0022). The mean total amount of paclitaxel in the peritoneal cavity at 23 h was 2.597 mg (+/-1.57) with hetastarch and 0.772 mg (+/-0.667) with peritoneal dialysis solution (P=0.0152).


CONCLUSIONS
These data show that hetastarch increased the exposure of peritoneal surfaces to paclitaxel by increasing the volume of solution with no decrease in drug concentration. Residual tumour cells within the peritoneal cavity may show an increased response to paclitaxel with hetastarch as a carrier solution.
Mohamed
F
F
The Washington Cancer Institute, Washington Hospital Center, 110 Irving Street, NW, Washington, DC 20010, USA.
Marchettini
P
P
Stuart
O A
OA
Yoo
D
D
Sugarbaker
P H
PH
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017024:Chemotherapy, Adjuvant; D002851:Chromatography, High Pressure Liquid; D015314:Dialysis Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D018709:Statistics, Nonparametric
D000972:Antineoplastic Agents, Phytogenic; D015314:Dialysis Solutions; D006895:Hydroxyethyl Starch Derivatives; D017239:Paclitaxel