Overcoming resistance to chronomodulated 5-fluorouracil and folinic acid by the addition of chronomodulated oxaliplatin in advanced colorectal cancerpatients

The addition of oxaliplatin (L-OHP) to a 5-fluorouracil (5-FU)/leucovorin ( FA) regimen was retrospectively evaluated in 35 consecutive advanced colore ctal cancer patients after progression of disease. L-OHP, 25 mg/m(2)/day, w as infused from 10.00-22.00 with a peak flow at 16.00 while 5-FU, 700 mg/m( 2)/day and FA, 150 mg/m(2)/day of the l-form or 300 mg/m(2)/day of the race mic form, from 22.00 to 10.00 with a nocturnal peak at 4.00, for 5 days eve ry 3 weeks in 24 patients and for 4 days every 2 weeks in the other 11. Dia rrhea and sensitive neuropathy were the most relevant types of toxicity (17 % of patients). An objective response was achieved in 8/35 patients (23%) [ 95% CL 9-37], stabilization in 15 patients (43%) which included five minor responses, and progression in 12. There was no relevant difference in quali ty of life assessed with the EORTC QLQ C30+3 questionnaire before and after treatment. Median duration of response and median progression-free surviva l were 6 months; median overall survival was 11 months. This retrospective study showed that it is possible to reverse resistance to chronomodulated 5 -FU by adding chronomodulated L-OHP to the previous regimen; comparison wit h different schedules of this combination should be performed in order to i dentify the best tolerated and active regimen as second-line treatment of a dvanced colorectal cancer. [(C) 2000 Lippincott Williams & Wilkins].