Summary
Tumor-tissue platinum levels and major pharmacokinetic parameters were determined in 11 patients with head and neck squamous cancer (HNSC) who were given cisplatin (50 mg/m2 daily x 2 days) and 5-fluorouracil (5-FU; 1000 mg/m2, continuous infusion x 5 days) either i.a. or i.v. The plasma peak platinum concentrations (c max) and the areas under the curve for total platinum concentration versus time (AUC) during i.a. infusions were lower than the i.v.c max (mean, 1.92±0.28 and 4.08±2.80 mg/l, for i.a. and i.v. infusions, respectively) and AUC values (mean, 22.55±4.96 and 40.66±10.71 mg h−1 l−1 for i.a. and i.v. treatment, respectively), suggesting a first-passage extraction of the drug by the tumor mass during i.a. infusion. However, no statistically significant difference was found in platinum tumor concentrations after i.a. administration versus i.v. infusion. The lack of a difference in tumor platinum concentrations between the i.a. and the i.v. administration routes might be explained either by a relatively high blood supply to the tumor area, enabling efflux of the surplus free platinum from the tissue, or by the delay between drug infusion and biopsy. After three cycles of i.a. treatment good tumor remission was obtained with minimal local toxicity. Larger clinical studies testing the advantages of the i.a. administration route over i.v. infusion appear to be necessary.
Abbreviations
- HNSC:
-
head and neck squamous cancer
- AUC:
-
area under the total platinum concentration versus time curve
- OS:
-
overall survival
- 5-FU:
-
5-fluorouracil
- DFS:
-
disease-free survival
- CR:
-
complete response
- PR:
-
partial response
- SD:
-
stable disease
- PRO:
-
progression
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This study was supported by grants from the AIRC (Italian Association for Cancer Research) and by grant from the Regione Veneto. One of the Authors (P.A.) is the recipient of an MPI 40% grant
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Sileni, V.C., Fosser, V., Maggian, P. et al. Pharmacokinetics and tumor concentration of intraarterial and intravenous cisplatin in patients with head and neck squamous cancer. Cancer Chemother. Pharmacol. 30, 221–225 (1992). https://doi.org/10.1007/BF00686317
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DOI: https://doi.org/10.1007/BF00686317