‘FOLFOX Should Be Considered as First-Line Standard of Care Over IFL or IROX’

August 1, 2003

This special supplement to Oncology News International includes 28 reportswith updated information on clinical trials investigating capecitabine and other agents inthe treatment of advanced colorectal and breast cancers, and other solid tumors.The reports summarize selected presentations from the 39th Annual Meeting of theAmerican Society of Clinical Oncology (ASCO) and related educational symposiaheld in conjunction with ASCO.

ROCHESTER, Minnesota-Maturedata from a phase III trial comparingthree multidrug regimens against advancedcolorectal cancer show that FOLFOX(infusional fluorouracil [5-FU], leucovorin,and oxaliplatin [Eloxatin])increased response rates and time to progression.Patients in the other experimentalarm of the trial received irinotecanplus oxaliplatin (IROX). Patients randomizedto the control arm received IFL (irinotecan[CPT-11, Camptosar] with bolus5-FU plus leucovorin).Richard M. Goldberg, MD, of the MayoClinic, Rochester, Minnesota, reportedthe findings (ASCO abstract 1009). "Basedon our results, FOLFOX should be considereda first-line standard of care overIFL or IROX," he said.Study Aims"The primary outcome was mediantime to tumor progression. Secondaryoutcomes were overall survival, responserate, quality of life, and toxicity," Dr. Goldbergexplained. "Treatment with FOLFOXresulted in significantly increasedtime to progression and response rateswhen compared to IFL and IROX. Bothoxaliplatin containing regimens, FOLFOXand IROX, were associated with a significantlyimproved overall survival comparedto IFL. The toxicity profile favoredFOLFOX over IFL with the exception ofparesthesias. Our quality of life tools failedto discern significant overall differencesbetween regimens."Eligibility criteria included: histologicdiagnosis of incurable colorectal cancer,age 18 or over, Eastern Cooperative OncologyGroup (ECOG) performance statusof 0 to 2, adequate organ function, andlife expectancy exceeding 12 weeks. Exclusioncriteria included: a second primarycancer within 5 years, prior chemotherapy for advanced disease, prior adjuvanttherapy completed less than 12months prior to the diagnosis of metastaticdisease, uncontrolled intercurrentillness, brain metastases, pregnancy orlactation, more than three stools daily,symptomatic sensory neuropathy or pulmonaryfibrosis.A total of 795 patients participated,divided almost evenly among the threestudy arms and with a median age of 61years for each arm. Between 92% and 93%of patients had ECOG performance scoresof 0 to 1.Study ResultsPreliminary results at 12 months follow-up were presented at the 2002 AmericanSociety of Clinical Oncology meeting(ASCO 2002 abstract S11). This year theinvestigators reported mature data with afollow-up of 20.4 months (ASCO abstract1009).About 85% of patients had progressivedisease and 65% had died. The 60-daymortality rates were similar: 4.5% for IFL,2.6% for FOLFOX, and 2.7% for IROX.Febrile neutropenia, diarrhea, andnausea and vomiting were significantlymore common with IROX. Paresthesiaswere significantly more common withFOLFOX."There was a statistically significantsurvival advantage to both experimentalregimens over IFL: median survival timeswere 14.8 months with IFL, 19.5 monthswith FOLFOX, and 17.4 months withIROX," Dr. Goldberg noted. "Survivalproportions at 1 year were: 59% for IFL,72% for FOLFOX, and 67% for IROX.Response rates were 31% for IFL, 45 % forFOLFOX, and 34% for IROX."Median time to progression, using theNorth Central Cancer Treatment Group(NCCTG) standard definition, was 6.9months for IFL, 8.7 months for FOLFOX,and 6.5 months for IROX. Because ofcontroversy regarding the NCCTG definitionof time to progression, the studyalso analyzed the data using a definitionemployed by the US Food and Drug Administration(FDA) to isolate the effect ofinitial treatment. Time to progressionfindings were not different using the seconddefinition.At the completion of the study specifiedtherapy, between 67% and 75% ofpatients had second-line treatment.Among patients randomized to IFL, 24%later received oxaliplatin. After FOLFOX,60% of patients received irinotecan. AfterIROX, 50% of patients received 5-FU.