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KMID : 0939920030350010025
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대한암학회지
2003 Volume.35 No. 1 p.25 ~ p.29
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Phase Ⅰ and Pharmacokinetic Study of Intraoperative Intraperitoneal Heptaplatin in Patients with Surgically Resected Advanced Gastric Cancer
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Yu Wan-Sik
Chung Ho-Young
Park So-Hyang
Cho Yong-Baik
Lim Yang-Soo
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Abstract
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Purpose: Heptaplatin, a new platinum analog, has favorable toxicity profiles and antitumor activity, comparable to those of cisplatin, in the treatment of gastric cancer. This study was designed to define the maximum tolerated dose (MTD),
dose-limiting toxicity (DLT) and pharmacokinetics of heptaplatin administered by an intraperitoneal route in patients with resected advanced gastric cancer.
Materials and Methods: Seventeen patients with resected advanced gastric cancer were entered onto the study. After completion of a curative resection and anastomosis, heptaplatin was administered intraperitoneally in one liter of 5%
dextrose
solution. The starting heptaplatin dose was 400 ㎎/㎡ of the body surface area, and was escalated in 200 ㎎/㎡ increments, to cohorts of three patients. A pharmacokinetic analysis was carried out to determine the total and ultrafiltratable
platinum
concentrations in the plasma, peritoneal fluid, and urine.
Results: Patients were unable to tolerate a 1,000 ㎎/㎡ dose level, and at 800 ㎎/㎡, reversible Grade Ⅲ toxicities, including elevated creatinine, proteinuria, hyponatremia, abdominal pain, and intraabdominal bleeding were noted. No
significant
toxicity was noted up to a 600 ㎎/㎡ dose level. The ratio of the peak peritoneal to peak plasma drug concentrations were 19.4, 16.6 and 22.8 at doses of 400 ㎎/㎡, 600 ㎎/㎡ and 800 ㎎/㎡, respectively. The pharmacological advantage, expressed as
the
peritoneal to plasma AUC ratio ranged from 4.3 to 7.0.
Conclusion: Heptaplatin can be delivered by an intraperitoneal route, with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure. The MTD of intraperitoneal heptaplatin was 800 ㎎/㎡. The major DLTs
were
nephrotoxicity and intraabdominal bleeding. The recommended starting dose for a subsequent study would be 600 ㎎/㎡.
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KEYWORD
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Intraoperative chemotherapy, Intraperitoneal chemotherapy, Heptaplatin, Pharmacokinetics, Stomach neoplasm
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