Cisplatin tumor concentrations after intra-arterial cisplatin infusion or embolization in patients with oral cancer.

Background: One neoadjuvant course of intra-arterial high-dose cisplatin (cis-diamminedichloroplatinum [CDDP]) tumor perfusion combined with intravenous sodium thiosulfate (STS) (cisplatin neutralizer) infusion is part of a multimodality concept for treatment of oral cancer. Recently, crystalline cisplatin embolization has been described as a novel treatment variant with increased tumor response rates.
Methods: We have compared tumor and plasma concentrations of cisplatin and STS by means of microdialysis in 10 patients with oral cancer treated with intra-arterial cisplatin perfusion (150 mg/m(2) in 500 mL of 0.9% sodium chloride) and 6 patients with oral cancer treated with crystalline cisplatin embolization (150 mg/m(2) in 45-60 mL of 0.9% sodium chloride), respectively. The microdialysis catheter was placed into the tumor, and the intra-arterial catheter into the tumor-feeding artery. Cisplatin was rapidly administered through the intra-arterial catheter and STS (9 g/m(2)) was infused intravenously to reduce the systemic toxicity of cisplatin. STS infusion was started 10 seconds after the cisplatin infusion was started.
Results: After embolization, cisplatin tumor maximum concentration (C(max)) and tumor area under the concentration-time curves (AUCs) were about 5 times higher than those achieved after intra-arterial perfusion (C(max), 180.3 +/- 62.3 micromol/L versus 37.6 +/- 8.9 micromol/L), whereas the opposite was true for plasma concentrations (C(max), 0.9 +/- 0.2 micromol/L versus 4.7 +/- 0.6 micromol/L). STS plasma levels were about 3 times higher than its tumor concentrations (C(max) tumor, 1685 +/- 151 micromol/L; C(max) plasma, 5051 +/- 381 micromol/L). After the standard intra-arterial perfusion, the average STS/CDDP AUC ratios for tumor and plasma were 211 +/- 75 and 984 +/- 139, respectively. After cisplatin embolization, the respective ratios were 48.5 +/- 29.5 and 42966 +/- 26728.
Conclusion: Molar STS/CDDP ratios of greater than 500 are required outside the tumor to neutralize cisplatin, whereas tumor ratios should be lower than 100 to avoid a loss of tumor cell killing. The first goal is achieved with both treatment modalities and the second only with cisplatin embolization, suggesting that crystalline cisplatin embolization is superior to intra-arterial cisplatin perfusion in terms of tumor cisplatin concentrations. Whether this translates into higher tumor response rates needs to be investigated further.