Oxaliplatin (OXA) plus folinic acid (FA) and 5-fluorouracil (FU) i.v. bolus (OXAFAFU) versus irinotecan (IRI) plus FA and FU i.v. bolus (IRIFAFU) in advanced colorectal carcinoma (ACC): Activity and toxicity results of the SICOG 0103 randomized trial

4143 Background: IRIFAFU regimen showed activity and toxicity similar to other IRI+FU based combinations in ACC (Comella et al, Ann Oncol 2002). Primary end-point of SICOG trial 0103 was to compare response rate (RR) of OXAFAFU with that of IRIFAFU in ACC. Methods: ACC patients (pts) with measurable disease randomly received: IRI 200 mg/m2 i.v. (90-min) on day 1, and l-FA 250 mg/m2 i.v. (2-hour) + FU 850 mg/m2 i.v. (bolus) on day 2 (IRIFAFU); or OXA 100 mg/m2 i.v. (2-hour) on day 1, and l-FA 250 mg/m2 i.v. (2-hour) + FU 1,050 mg/m2 i.v. (bolus) on day 2 (OXAFAFU high dose [HD]); both regimens were given every 2 weeks. After a planned interim analysis on the first 145 treated pts, OXA was reduced to 85 mg/m2, and FU to 850 mg/m2 (OXAFAFU low dose[LD]). Results: From January 2001 to June 2003, 274 (135 IRIFAFU, 71 OXAFAFUHD, 68 OXAFAFULD) pts were treated. Pre-treatment characteristics according to arms: PS=1–2: 54/38/26; adjuvant FAFU: 34/19/15; two or more disease sites: 63/40/31; liver mets: 99/56/52. WHO toxicity (% pts) according to arms: febrile neutropenia= 4/10/1.5; Grade 4 neutropenia=14/35/19; Grade 3 or more diarrhea=25/10/10. Sixty-day mortality rate=4.4/4.2/4.3. Lévi Grade 3 neuropathy occurred in 11%/3% of pts treated with OXAFAFUHD/OXAFAFULD. RR according to arms: IRIFAFU=31%, OXAFAFUHD=41%, OXAFAFULD=44%. After a median follow-up of 19 months, 166 (60%) pts showed progression, and 118 (43%) pts died: overall median progression-free and survival times were 7.7 and 17.3 months. Numbers of events are still few for comparative analysis. Conclusions: OXAFAFULD regimen produced a significantly greater RR (Fisher's test, p=0.0478), and a lower toxicity than IRIFAFU. Updated results on progression-free and overall survival according to arm of treatment will be presented at the time of the meeting. No significant financial relationships to disclose.