Pharmacokinetics of Cisplatin in the Systemic versus Hyperthermic Intrathoracic or Intraperitoneal Chemotherapy

Objective: To compare the pharmacokinetics of cisplatin in the systemic chemotherapy (SC) versus in the hyperthermic intrathoracic chemotherapy (HITHOC) or hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: Total 60 patients were enrolled into this study. After administering same dose of cisplatin via intravenous infusion (SC group), HITHOC or HIPEC procedure, concentration of cisplatin in the plasma and in the hyperthermic perfusion solution at various time points was quantified by HPLC analysis. The area under the plasma or perfusion solution concentration-time curve over the last 24h dosing interval (AUC0-24 h) were calculated and compared. Results: In the perfusion solution, HITHOC group AUC0-24 h of cisplatin was significantly higher than that of HIPEC group (72.36 µg/mL·h vs 36.03 µg/mL·h, p < 0.01). In contrast, in the plasma, HITHOC group AUC0-24 h of cisplatin (2.57 µg/mL·h) was significantly lower than that of HIPEC group (3.02 µg/mL·h, p < 0.01) or SC group (3.15 µg/mL·h, p < 0.01). Absolute bioavailability of cisplatin in the thoracic and abdominal cavities was 23 and 11 times higher than that in the blood (SC group), respectively. Conclusion: This study demonstrated that administration of cisplatin via HITHOC or HIPEC results in significantly higher AUC0-24 h in the thoracic or abdominal cavities, but similar level of AUC0-24 h in the blood circulation compared to the group administered via intravenous infusion. This study provided pharmacokinetic evidence to further support the concept that topical application of cisplatin during HITHOC or HIPEC is superior to systemic chemotherapy for the malignant pleural effusion or ascites treatment.