Oxaliplatin (L-OHP) in combination with 5-fluorouracil (5-FU)/l-leucovorin (l-LV) on modified Roswell Park regimen as first-line treatment of advanced colorectal cancer (ACRC): A phase I/II study

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Abstract
3705 Background: L-OHP has been established as a key drug for ACRC, and FOLFOX 4 is commonly used in Europe and the US. We conducted this trial to determine the recommended dose (RD) and evaluate safety and efficacy of L-OHP + weekly bolus 5-FU/l-LV as first-line treatment of ACRC. Methods: Inclusion criteria were unresectable ACRC, no prior chemotherapy, PS (ECOG) 0–2, age 20 - 75 years, measurable lesions, and adequate organ functions. L-OHP was administered over 2 hours (hrs) IV on days 1, and 15 with l-LV over 2 hrs IV and 5-FU IV bolus on days 1, 8, and 15 every 28 days. Doses of L-OHP and l-LV were fixed at 85 mg/m2 and 250 mg/m2 respectively, and that of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2). RD was determined in a formal phase I dose escalation manner, and safety and efficacy were evaluated according to NCI-CTC v2.0 and RECIST guidelines. Results: No dose-limiting toxicity (DLT) was observed at level 1 (n = 3), but at level 2 (n = 4), 3 patients (pts) experienced DLTs in the first cycles; grade (G) 3 thrombocytopenia, G4 neutropenia, and G2 neutropenia required treatment delay over 7 days. Level 1 was therefore determined as the RD, and 11 pts more were accrued at this dose. A total of 18 pts (14 at RD) were enrolled. Male /female = 11/7, PS 0/1/2 = 15/3/0, median age 63 years (range 37 - 73), colon/rectum = 14/4. Median number of cycles treated was 5.5. Peripheral neuropathy was observed in all 18 pts, but with no functional impairment. G3 toxicities at RD were as follows: neutropenia in 2 pts, hemoglobin decreased, lymphopenia in 1 pt each. Overall response rate was 61% (CR/PR/SD/PD=0/11/7/0). Median progression-free survival was 170 days. Conclusions: L-OHP + weekly bolus 5-FU/l-LV regimen was well tolerated. Efficacy and safety appear to be comparable to those of FOLFOX 4. (Supported by Yakult Honsha Co., Ltd.) No significant financial relationships to disclose.

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