Oxaliplatin (L-OHP) and irinotecan (CPT-11) with 6s-leucovorin (IFA)-modulated 5-fluorouracil (FU) i.v. bolus every 2 weeks: a dose-finding study in patients (pts) with gastrointestinal malignancies

Purpose: In our previous studies we have established that IRI can be combined with FA-modulated FlJ iv bolus every 2 wks, producing an interesting response rate (RR) in ACC. The aim of this study was to compare the activity and toxicity of this new regimen with doubly-modulated FU.Methods: Pts with measurable ACC were randomly allocated to receive: tR1 200 mgIm2 (1-h iv infusion) on d 1, FA 250 mg/m2.(2-h iv infusion)+ FU 850 mg/m2 (iv bolus) on d 2 q 2 wks (IRIFAFU), or MTX 750 mg/m2 (2-h iv infusion) on d 1, FA 250 mg/m2 (2-h iv. infusion)+ FU 800 mg/m2 (iv. bolus) on d 2 q 2 wks (MTXFAFU). RR and time to progression (TTP) were the main end-points of this study. Results: From June 1998 to December 2000, 234 eligible patients were enrolled: median age 63 (range, 29-79) yrs; M/F= 136/9&’ECGG PS O/l/2= 136/85/11; colon/rectum= 168/66; previous adjuvant FAFU= 65; disease sites 1/2KI= 130/78/26; liver/lung mets= 167/52: As of March 31, 2001, confirmed responses were 41 (9 CRs) with IRIFAFU (RR= 35%), and 23 (4 CRs) with MTXFAFU (RR= 20%)(~~ 0.02); control of tumor growth was obtained in 60% and. 4&3% of pts, respectively,(pt0. 05). Median lTP was 7.3 vs 4.4 mo.(pcO. 03). Wfih 48% of pts censored, survival data are not mature yet. 976 courses of IRIFAFU and 795 of MTXFAFU were analysed for WHO toxicity: grade 3-4 neutropenia was reported in 41% and 10% of pts (p< O. OOl), and diarrhoea in 13% and 4% of pts (pcO. OOl), respectively.Conclusion: Our IRIFAFU regimen is comparable with other weekly or biweekly combinations in terms of both activity and toxicity; however, our IRIFAFU is time-sparing, and it …