SP-0452: Towards individualised dose-constraints for dose-limiting toxicity

Redefining dose-limiting toxicity.

Liposomal cisplatin dose escalation for determining the maximum tolerated dose and dose-limiting toxicity: a phase I study.

BACKGROUND The aim of the present trial was to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of liposomal cisplatin (lipoplatin) using nephrotoxicity, gastrointestinal toxicity and myelotoxicity as the main adverse reactions. PATIENTS AND METHODS Lipoplatin, a liposomal formulation of cisplatin was first tested as monotherapy starting at a dose of 125 mg/m(2) and...

Single Dose Acute Toxicity Testing

Consensus Regarding new Drug Applications. " The Agency has revised this guidance based on comments it received on the proposed implementation. This approach, designed to facilitate the early stages of pharmaceutical development, is not and ICH consensus position although it is considered to be in general agreement with the ICH position on acute toxicity testing. This guidance was published in ...

Vincristine toxicity unrelated to dose.

Four children with vincristine toxicity unrelated to dose are described. Fever, haematological toxicity, and abdominal distension occurred 2-7 days after vincristine was given. Convulsions occurred 6-8 days after vincristine in all 4. Inappropriate secretion of antidiuretic hormone was thought to have occurred in 3 patients. 2 patients died during the acute toxicity phase. Necropsy findings did...

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects.

PURPOSE Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradi...