XELOX Shows Favorable Safety Profile vs FOLFOX6 in Metastatic Colorectal Cancer

August 1, 2005

VILLEJUIF, FRANCE-In thefirst randomized comparison of aschedule of FOLFOX6 (fluorouracil[5-FU], leucovorin, oxaliplatin [Eloxatin])vs standard XELOX (capecitab

VILLEJUIF, FRANCE-In thefirst randomized comparison of aschedule of FOLFOX6 (fluorouracil[5-FU], leucovorin, oxaliplatin [Eloxatin])vs standard XELOX (capecitabine[Xeloda]/oxaliplatin) in metatstaticcolorectal cancer, XELOX was shownto have a favorable safety profile (abstract3596).Preliminary Analysis ofXELOX FavorableLead investigator Michel Ducreux,MD, PhD, of Institut Gustave Roussyin Villejuif, France, revealed that theFOLFOX6 regimen is relatively commonin France."If final results of this study confirmthe preliminary analyses," the investigatorsconcluded, "XELOX offersbenefits to the patient in terms of clinicalsafety:

  • similar rates of diarrhea, nausea,vomiting, fever, and asthenia, butmore hand-foot syndrome;
  • less paresthesia, neuropathy, andneutropenia."

In this phase III multicenter Frenchtrial, the most common clinical adverseevents for both regimens wereparesthesia, diarrhea, nausea, vomiting,and asthenia (see Table 1). Grade3/4 clinical adverse events occurred inless than 15% of patients. XELOX ledto fewer cases of grade 3/4 paresthesiaand neuropathy but more cases of diarrhea,asthenia, and vomiting. Onepatient in each arm experienced grade3/4 chest pain, and one toxic deathoccurred in each arm.

Overall, patients in the arm receivingXELOX experienced fewer hematologicadverse events, including neutropenia,thrombocytopenia, anemia,and febrile neutropenia (see Table 2).Among grade 3/4 hematologic adverseevents, XELOX was associated withless neutropenia but more thrombocytopenia.

Treatment Cycles Vary

Of the 177 patients in the study, 91were randomized to receive XELOXand 86, FOLFOX6. The XELOX regi-men consisted of oral capecitabine(1,000 mg/m

2

twice daily on days 1 to14) and oxaliplatin (130 mg/m

2

via 2-hour infusion on day 1). The FOLFOX6regimen consisted of 5-FU (400mg/m

2

IV bolus on day 1), followed by2,400 to 3,000 mg/m

2

as a 46-hourinfusion, in addition to leucovorin(400 mg/m

2

) and oxaliplatin (100 mg/m

2

via 2-hour infusion on day 1).The XELOX cycle was 3 weeks longand the FOLFOX6 cycle was 2 weekslong. The median number of cyclescompleted was 6 (range 1-8) for XELOXand 11 (range 1-12) for FOLFOX6.More than 90% of patients in thestudy had an Eastern Cooperative OncologyGroup (ECOG) performancestatus of 0 to 1. Patient characteristicswere generally well matched. Eligiblepatients could have undergone no priortreatment for metastatic disease,although 20% of FOLFOX6 patientsand 28% of XELOX patients had undergoneprevious adjuvant chemotherapy,mostly 5-FU-based therapy.Trial enrollment was expected to becompleted in summer 2005.