Circadian optimisation of irinotecan and oxaliplatin efficacy in mice with Glasgow osteosarcoma

The relevance of circadian rhythms in irinotecan and oxaliplatin tolerability was investigated with regard to antitumour activity. Mice bearing Glasgow osteosarcoma (GOS) received single agent irinotecan (50 or 60 mg kg −1 per day) or oxaliplatin (4 or 5.25 mg kg −1 per day) at one of six dosing times expressed in hours after light onset (3, 7, 11, 15, 19 or 23 hours after light onset). Irinotecan (50 mg kg −1 per day) and oxaliplatin (4 or 5.25 mg kg −1 per day) were given 1 min apart at 7 or 15 hours after light onset, or at their respective times of best tolerability (7 hours after light onset for irinotecan and 15 hours after light onset for oxaliplatin) or worst tolerability (15 hours after light onset for irinotecan and 7 hours after light onset for oxaliplatin). Tumour growth rate was nearly halved and per cent increase in estimated life span (% ILS) was – doubled in the mice receiving irinotecan at 7 hours after light onset as compared to 15 hours after light onset ( P