Choice of Starting Dose for Molecularly Targeted Agents Evaluated in First-in-Human Phase I Cancer Clinical Trials

Purpose: One tenth of the lethal dose to 10% of mice is one of the conventional parameters used to derive a safe starting dose in phase I trials of cytotoxic agents. There is no consensus on which preclinical models and parameters should define the starting dose for molecularly targeted agents.

Phase I Oncology Studies: Evidence That in the Era of Targeted Therapies Patients on Lower Doses Do Not Fare Worse — Dr Maurie Markman et al

abstract:

"Purpose: To safely assess new drugs, cancer patients in initial cohorts of phase I oncology studies receive low drug doses. Doses are successively increased until the maximum tolerated dose (MTD) is determined. Because traditional chemotherapy is often more effective near the MTD, ethical concerns have been raised about administration of low drug doses to phase I patients. However, a substantial portion of oncology trials now investigate targeted agents, which may have different dose-response relationships than cytotoxic chemotherapies.......

Finding the Right Dose for Cancer Therapeutics—Can We Do Better? — Clinical Cancer Research

Note: very short abstract as below, but good points (in the absence of the full paper)

Abstract:
"Unlike other diseases, dose-selection for cancer therapeutics is often based on the maximum-tolerated dose in phase 1 studies involving relatively few patients. In this issue of Clinical Cancer Research, Jain and colleagues provide evidence that lower doses may be as effective as maximum-tolerated doses in the treatment of cancer patients."