CAPOX Demonstrates Equivalent Efficacy and Toxicity to FUFOX in First-Line Setting for Patients With Advanced Colorectal Cancer

BREMEN, GERMANY-CAPOXand FUFOX have comparabletoxicity profiles and efficacy in thefirst-line treatment of metastatic colorectalcancer, according to a phase IIIGerman study. "Offering the convenienceof an oral regimen, CAPOX is apossible alternative to FUFOX," concludedthe study's lead investigator,Hendrik-Tobias Arkenau, MD, ofHospital Bremen East in Bremen, Germany(abstract 3507).The study randomized 476 patientsto receive one of the two followingregimens:

• CAPOX (capecitabine [Xeloda],1,000 mg/m² twice daily on days 1-14;oxaliplatin [Eloxatin], 70 mg/m² ondays 1 and 8) every 3 weeks
• FUFOX (fluorouracil, 2,000 mg/m² as a 24-hour infusion; folinic acid,500 mg/m²; oxaliplatin, 50 mg/m² ondays 1, 8, 15, and 22) every 5 weeks.

All patients had measurable disease,an Eastern Cooperative OncologyGroup (ECOG) performance statusof 0 to 2, and normal renal andhepatic function. Baseline characteristicswere well balanced for the 242patients in the CAPOX arm and the234 patients in the FUFOX arm. Themedian age of patients was 66 years inthe CAPOX arm and 64 years in theFUFOX arm.

Toxicity and Response

The two regimens had comparabletoxicity profiles, although there wasmore hand-foot syndrome, particularlygrade 2/3, in the CAPOX arm.The most common grade 3/4 clinicaladverse event was neurosensorytoxicity.The study was based on a noninferioritydesign, and CAPOX showed noinferiority compared with FUFOXwithin the investigators' statistical assumptions.Study results follow for CAPOX vsFUFOX:

• Overall response rates were 47%for CAPOX (95% CI, 41%-54%) vs49% for FUFOX (95% CI, 43%-56%),with complete response rates of 2% vs5%, partial response of 45% vs 44%,and stable disease in 27% vs 24%.
• Median progression-free survivalwas 7 vs 8 months (P =.11).
• Median overall survival was 16.3vs 17.2 months (P = .72)

"Like the safety analysis, there is nodifference in response rates," Dr.Arkenau reported.

Caution Advised

"Overall, this important study validatescapecitabine as an acceptablealternative to infusional 5-FU in combinationwith oxaliplatin," noted NealJ. Meropol, MD, of Fox Chase CancerCenter in Philadelphia, who served asa discussant for this ASCO presentation."In interpreting these results, oneshould note that studies in Europeand North America have been discordantin terms of doses of capecitabinethat are tolerable in combination withoxaliplatin," Dr. Meropol said. "Althougha mechanism for this discordancehas not been elucidated, it suggeststhat some caution is required inapplying the results of this trial to thecare of patients worldwide."