Platinum dose-intensity.

Abstract

The rationale for platinum dose-intensity is based on pharmacologic principles, laboratory observations, and retrospective analysis of clinical studies. However, prospective studies have indicated that dose-intensity studies have been limited by toxicities, restricting the dose increase for cisplatin to approximately twice the conventional dose and for carboplatin two- to three-fold the standard AUC. Phase I and II studies indicated that the response rates for high-dose carboplatin with hematopoietic cell support improved significantly but were short lasting, lacking a significant effect on survival. Recently, a new IA dose-intensity approach employing extremely high and locally administered cisplatin doses with systemic neutralization, demonstrated a very high response rate in advanced head and neck cancer. Overall, high-dose intensity of platinums may potentially increase treatment efficacy in tumors sensitive to platinum containing drugs. Successful examples are the high dose carboplatin with hematopoietic support and the IA high-dose cisplatin approach with systemic neutralization. However, the key to future success will depend on the selection of patients with drug sensitive tumors.