An effective combination partner

Xeloda^© is an effective, well-tolerated and convenient alternative to i.v. 5-FU in combination with other highly active treatments in colorectal cancer. Various combination regimens of Xeloda^© with oxaliplatin, irinotecan, biological agents or radiotherapy have been studied in phase I and II studies. Phase III trials are now underway.

Xeloda^© /oxaliplatin (XELOX). The dosing schedule recommended for phase II evaluation of XELOX was i.v. oxaliplatin, 130 mg/m2 on day 1, followed by Xeloda^© , 1000 mg/m2 twice daily on days 1–14, every 21 days.1 Several phase III studies are now under way to compare XELOX with various oxaliplatin/5-FU/LV regimens in the adjuvant setting (Dukes' C colon carcinoma) and as first- and second-line treatment of metastatic colorectal cancer.

• Preliminary safety data from the phase III XELOXA trial showed that XELOX results in less myelosuppression and stomatitis than 5-FU/LV, but more skin and neurosensory toxicities. Cross-study comparisons with the MOSAIC and NSABP C-17 trials,^2,3 show that XELOX has a comparable safety profile to FOLFOX and compares favourably to FLOX, with the added benefit of improved convenience of an oral chemotherapy-based regimen.⁴ XELOX leads to a lower incidence of nausea, vomiting and diarrhoea compared with FLOX.³
• In a phase II study of 96 previously untreated patients with metastatic disease, XELOX achieved an objective response rate of 55%, with an additional 32% of patients having stable disease for at least 3 months.⁵
• The efficacy profile of XELOX compares favourably with 5-FU/LV plus oxaliplatin (FOLFOX-4). The safety profile of XELOX is also similar, but with a lower incidence of grade 3/4 neutropenia than FOLFOX-4.⁶
• Phase III trials comparing Xeloda^© -based regimens with 5-FU-based regimens have since reinforced the phase II data, demonstrating that patients receiving Xeloda^© /oxaliplatin have comparable responses to those receiving 5-FU/LV/oxaliplatin.7,8 The incidence of grade 3 or 4 toxicities are similar in both regimens, though diarrhoea (11.2 vs 17.1 %), neutropenia (3.7 vs 6.7%) and vomiting (5.2 vs 6.0%) occurred less frequently with Xeloda^© /oxaliplatin than 5-FU/LV/oxaliplatin.⁷
• Additionally, in a human xenograft model, XELOX inhibited the in vivo growth of CXF280 human colon cancer cell line more effectively than Xeloda^© or oxaliplatin alone.⁹

Therefore, due to its at least equivalent efficacy and favourable safety profile, XELOX should be considered as a more convenient option to 5-FU-based regimens in both the adjuvant and metastatic settings.