A phase II randomized study of Combined Infusional Leucovorin Sodium and 5- FU versus the Leucovorin Calcium followed by 5-FU both in combination with Irinotecan or Oxaliplatin in patients with metastatic colorectal cancer

Background : Leucovorin Sodium (LV/Na) has a high solubility, and is stable when given with continuous infusion of 5-FU. It could maintain significant plasma concentration of 5, 10-meTHF during the whole 5-FU perfusion with the potential of increasing 5-FU cytotoxicity. We conducted a randomized phase II clinical trial on leucovorin calcium (LV/Ca) and LV/Na in metastatic colorectal cancer patients (mCRC). Main objectives were to assess efficacy and safety. Patients and methods : Fifty seven patients with mCRC and no previous chemotherapy for metastatic disease were randomized to receive LV/Na or LV/Ca with irinotecan or oxaliplatine combined with infusional 5-FU. LV/Na was defined as warranting further evaluation in phase III if true overall response rate (ORR) > 35% (a=5%, ss=10% in case of true ORR >55%, 51 evaluable patients planned/arm). Results : Results for LV/Ca and LV/Na arm respectively were : observed ORR, 55% (significantly higher than 35%, p = 0.02) and 61% (p = 0.004). Median overall survival durations were 11.9 months and 22.9 months (p = 0.02) and PFS 8.0 vs. 11.5 months (ns). Grade = 3 events were 64% and 46% (p = 0.28). Conclusion : Both LV/Na and LV/Ca disclosed an ORR > 35% with comparable safety. (Acta gastroenterol. belg., 2012, 75, 14-21).