Chronobiological concepts underlying the chronotherapy of human lung cancer

This article reviews the experimental and clinical data that form the basis for the chronotherapy of lung carcinoma, specifically, nonsmall cell lung cancer (NSCLC). Circadian rhythms in cell kinetics, immunological and endocrinological endpoints, and tumor markers are reviewed. Chronopharmacology and chronotolerance studies on laboratory animals and clinical observations on cancer patients involving the main drugs active in lung carcinoma have prompted prospective Phase I-III studies to evaluate the application of chronobiologic concepts in the treatment of NSCLC. Circadian rhythmicity in host tolerance (chronotolerance) to medications has been confirmed in two prospective randomized lung cancer trials; a large phase II study has established the value of chronobiologic concepts to improve the therapeutic index of advanced NSCLC.