ABSTRACT
Oxaliplatin is a novel platinum derivative and the first platinum compound to demonstrate significant efficacy in the treatment of advanced colorectal cancer (see also Chapter 50). In vitro and in vivo preclinical studies on colorectal cancer have shown that oxaliplatin is active against colorectal cell lines and is synergistic with 5-fluorouracil (5-FU).1 Furthermore, phase II trials of oxaliplatin monotherapy in previously treated or untreated patients with colorectal cancer have shown response rates of between 10% and 24%, with acceptable toxicity.2-4 Oxaliplatin has also been used in combination with leucovorin (LV; folinic acid) and 5-FU continuous infusion. The first studies concerned a 5-day chronomodulated regimen.5 Irinotecan (CPT-11) is a semisynthetic camptothecin analogue that has activity against advanced colorectal cancer cells6 – see also Chapter 49. Phase II trials have demonstrated that this agent is effective in patients whose disease has progressed on 5-FUbased therapy.7-9 The efficacy and low toxicity of the bimonthly LV/5-FU regimens10-13 allowed combination with the other active antitumour drugs in colorectal cancer therapy. FOLFOX (folinic acid, 5-FU, oxaliplatin) and FOLFIRI (folinic acid, 5-FU, irinotecan) refer to a series of trials combining bimonthly 48-hour LV/5-FU regimens with oxaliplatin or irinotecan at different doses.14
