XELOX With Bevacizumab Is Highly Active in Metastatic Colorectal Ca, Preliminary Data Show

August 1, 2005

DURHAM, North Carolina-The addition of bevacizumab(Avastin) to XELOX (capecitabine[Xeloda] and oxaliplatin [Eloxatin])results in a new, highly active regimen

DURHAM, North Carolina-The addition of bevacizumab(Avastin) to XELOX (capecitabine[Xeloda] and oxaliplatin [Eloxatin])results in a new, highly active regimenfor treating metastatic colorectal cancer(XELOXA), according to preliminaryevidence from a phase II trial(abstract 3556). "The reported mediantime to progression is among thehighest yet obtained in the first-linetreatment of metastatic colorectal cancer,"concluded Nishan Fernando,MD, and colleagues at Duke Universityin Durham, North Carolina.Convenient AlternativeXELOXA was investigated as a moreconvenient alternative to FOLFOX(fluorouracil [5-FU], leucovorin, oxaliplatin).The investigators noted thatFOLFOX "is superior to bolus IFL"(irinotecan [Camptosar], 5-FU, leucovorin)but "requires the inconvenienceof an ambulatory infusionpump."Patients with untreated metastaticcolorectal cancer initially receivedcapecitabine (1,000 mg/m2) twice dailyon days 1 to 5 and 8 to 12, in additionto oxaliplatin (85 mg/m2) on day1 and bevacizumab (10 mg/kg) on day1. The capecitabine starting dose wasreduced to 850 mg/m2 twice daily dueto toxicity in the first 27 patients. Thisreduced dose "appears to be bettertolerated," according to the investigators.The median age of the patientstreated was 55.5 years (range, 24-76years).Response and ToxicityAmong the first 30 patients receivingtherapy, 1 had a complete responseand 16 had partial responses (responserate, 57%; 95% confidence interval[CI]: 37%-75%). Eleven patients(37%) had stable disease. The mediantime to disease progression was 11.9months.During treatment, 20 of the first 30patients (66%) receiving therapy requiredat least one dose reduction ofcapecitabine, and 12 patients (40%)required two or more dose reductions,typically for diarrhea or hand-foot syndrome.Diarrhea occurred in 22 of 30patients (73%); 9 patients (30%) experiencedgrade 3 diarrhea, but therewere no cases of grade 4 diarrhea. Ofthe three patients who started at thereduced dose of capecitabine (850 mg/m2 twice daily), none experienced >grade 1 diarrhea. Hand-foot syndromewas observed in 63% of patients: 6patients (20%) with grade 1, 12 (40%)with grade 2, 9 (30%) with grade 3,and 0 with grade 4. Other toxicitiesincluded grade 3 peripheral neuropathy(10%), neutropenia (7%), andnausea and vomiting (7%).