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

Abstract

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.

Prediction of treatment outcome by cisplatin‐DNA adduct formation in patients with stage III/IV head and neck squamous cell carcinoma, treated by concurrent cisplatin‐radiation (RADPLAT)

“…Most studies measured intratumoral platinum content instead of cisplatin-DNA adducts in HNSCC patients [24][25][26][27] or cervical cancer patients. [28][29][30] Gouyette et al reported on intratumoral platinum content in HNSCC patients after cisplatin administration IV or IA. 24 Platinum concentrations in biopsies taken after IA infusion were slightly increased relative to IV treatment, but not statistically different.…”

Combining iodine-131 Lipiodol therapy with low-dose cisplatin as a radiosensitiser: preliminary results in hepatocellular carcinoma

“…The precise biochemical mechanisms of the interaction with radiation remain a matter of debate [8], but most arguments point to an inhibition of repair of sublethal damage by cisplatin through DNA cross-linkage. Experimental data indicate a non-saturable dose-dependency and time-dependency, with a tumour half-life of 94.4 h [9].…”

“…platin dose of 5-6 mg/m 2 [10] and these lower daily doses have been associated with sub-radiosensitising tumour concentrations [9]. 3.…”

Synergistic Anticancer Activity of 5-Aminolevulinic Acid Photodynamic Therapy in Combination with Low-dose Cisplatin on Hela Cells

“…The cisplatin is an effective DNA crosslinking agent and it has been suggested that low-dose cisplatin could make the tumor cell radiosensitive and inhibit DNA repair processes (Fu et al, 1988;Lagrange et al, 1996). The accumulation of p53 is a key event in cisplatin-associated chemotherapy .…”