Tumoral platinum concentrations in patients treated with repeated low-dose cisplatin as a radiosensitizer

The aim of the present study was to check whether platinum (Pt) concentrations achieved in tumors with a daily low-dose schedule were close to those promoting radiosensitization. Fifteen previously untreated patients with histologically proven advanced uterine cervix tumors were studied. They received a daily irradiation 30 min after a short infusion of 5 mg cisplatin for 5 consecutive days every week. A biopsy was taken from the accessible tumor mass, 4 to 6 hr after the daily injection. Blood samples were obtained once a week, just before the daily injection (H0) and 30 min after (H30). Quantificative analysis of Pt concentrations was performed by atomic absorption spectrophotometry. Plasma and tumoral Pt concentrations exhibited a marked intersubject variability. The median tumoral Pt concentration was 1,710 mg/g. Median total and ultrafiltrable Pt concentrations in plasma taken at H0 and H30 were 231 and 360 ng/ml, and 7 and 90 ng/ml respectively. Tumoral and total plasma Pt concentrations significantly increased during the course of treatment. Present data show that tumoral Pt concentrations achieved with this CDDP schedule are in the range of tumoral Pt concentrations previously shown to promote radiosensitization (2,000 ng/g). These results suggest that this CDDP radiosensitization regimen might be started with higher CDDP doses in order to reach earlier radiosensitizing Pt tumoral concentrations.