Cisplatin Concentrations in Long and Short Duration Infusion: Implications for the Optimal Time of Radiation Delivery

Abstract

Introduction: Cisplatin has radiosensitizing properties and the best sensitization to radiotherapy occurs with a higher plasma concentration of cisplatin. To our knowledge the optimal time sequence between chemotherapy and administration of radiation therapy, to obtain maximum effect from concurrent chemoradiation is unclear.

Aim: The aim of this study was to measure the two cisplatin infusion regimens in order to determine the total and free cisplatin post infusion concentration changes over time. These changes may have clinical implications on the optimum time of administration of post infusion radiation therapy.

Materials and methods: Two cohorts of patients were recruited and both, total and free plasma concentration of cisplatin following long and short durations of intravenous infusion was determined. Blood samples were collected at 0.5, 1, 1.5, 2, 3 and 5 hours from the start of the infusion in the 1hour infusion group and at 2, 3, 3.5, 4, 6 and 24 hours from the start of the infusion, in the 3 hour infusion group. Total and free cisplatin concentrations were measured using a validated HPLC-UV method.

Results: The highest concentration of total and free cisplatin was achieved at the end of the infusion in both regimens. Total cisplatin concentration declined 30 minutes after the end of infusion in both the groups. After 1hour of discontinuing cisplatin, the free cisplatin concentration also declined significantly.

Conclusion: We conclude that radiation should be administered within 30 minutes of completion of the infusion irrespective of the duration of infusion.

Keywords: Chemotherapy; Radiation therapy; Radiosensitizing.

[Table/Fig-1]:

Algorithm for the study.

[Table/Fig-3]:

Mean concentration time profiles of 1 hr and 3hr infusion regimens for cisplatin.