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 perfu-
sion (C
max
, 180.3 62.3 mol/L versus 37.6 8.9 mol/L), whereas the opposite was true for plasma
concentrations (C
max
, 0.9 0.2 mol/L versus 4.7 0.6 mol/L). STS plasma levels were about 3 times
higher than its tumor concentrations (C
max
tumor, 1685 151 mol/L; C
max
plasma, 5051 381
mol/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 42,966 26,728.
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.
(Clin Pharmacol Ther 2003;73:417-26.)
Irmgard Tegeder, MD, Lutz Bra ¨utigam, BS, Maic Seegel, Ahmed Al-Dam, Bernd
Turowski, MD, Gerd Geisslinger, MD, PhD, and Adorja ´n F. Kova ´cs, MD, DMD
Frankfurt am Main, Germany
Neoadjuvant intra-arterial (IA) chemotherapy with
cisplatin (cis-diamminedichloroplatinum [CDDP]) has
been successfully used as part of a multimodality ther-
apy for all stages of primary squamous cell carcinoma
of the oral cavity.
1-4
The selection of the IA route for
the administration of cisplatin is based on the premise
that this approach should result in greater total drug
exposure for the tumor and a reduction of its toxicity
for the rest of the body. The relative advantage of the
IA administration as opposed to the intravenous route is
a function of the clearance of the drug and tumor blood
From pharmazentrum frankfurt, Klinik und Poliklinik fu ¨r Kiefer und
Plastische Gesichtschirurgie, and Institut fu ¨r Neuroradiologie,
Klinikum der Johann Wolfgang Goethe-Universita ¨t.
Supported in part by the Paul and Willi Weil Stiftung.
Received for publication Oct 1, 2002; accepted Jan 2, 2003.
Reprint requests: Irmgard Tegeder, MD, pharmazentrum frankfurt,
Klinikum der Johann Wolfgang Goethe-Universita ¨t, Theodor Stern
Kai 7, 60590, Frankfurt am Main, Germany.
E-mail: tegeder@em.uni-frankfurt.de
Copyright © 2003 by the American Society for Clinical Pharmacol-
ogy & Therapeutics.
0009-9236/2003/$30.00 + 0
doi:10.1016/S0009-9236(03)00008-0
417