SYNERGISTIC ACTIVITY OF OXALIPLATIN AND 5-FLUOROURACIL IN PATIENTS WITH METASTATIC COLORECTAL-CANCER WITH PROGRESSIVE DISEASE WHILE ON OR AFTER 5-FLUOROURACIL

From February 1995 through October 1996, 25 patients with metastatic c olorectal cancer showing a clinical resistance to 5-fluorouracil (5-FU ) entered this study. Thirteen received oxaliplatin alone and 12 recei ved it in combination with 5-FU. Oxaliplatin was administered at 130 m g/m(2) over a 2-hour infusion every 3 weeks, alone or added either to 5-FU as a continuous infusion at 200 mg/m(2) to 300 mg/m(2) (six patie nts) or to a 5-FU bolus, 375 mg/m(2), plus leucovorin, 100 mg/m(2) dai ly for 5 days every 3 weeks (6 patients). Eighty-six of 98 administere d cycles were evaluable for toxicity (47 for oxaliplatin plus 5-FU and 39 for oxaliplatin alone). Hematologic toxicity was mild, occurring a s grade 2 leukopenia in 23% of the cycles of 5-FU and oxaliplatin and in 5% of the cycles of oxaliplatin alone. The most common toxicity was neurologic (grade 1 to 2 in 60%-6% of the cycles of the combination, respectively, and 68%-10% of oxaliplatin given alone) as hand-foot par esthesia or hypersensitivity to cold. No grade 4 toxicity was reported and only three patients in the 5-FU group developed grade 3 diarrhea. Grade 2 nausea and vomiting occurred in 33% of the cycles when both d rugs were given and in 15% when oxaliplatin was administered alone. Th e combination of oxaliplatin and 5-FU induced four partial remissions (33%; 95% confidence interval, 6%-60%), whereas eight patients of the whole group had stable disease. No response occurred when oxaliplatin was administered as a single agent. The results of this study confirm the antitumor activity of oxaliplatin when added to 5-FU in patients w ho have metastatic colorectal cancer previously refractory to 5-FU. Th e possible therapeutic synergy with 5-FU was not accompanied by increa sed toxicity.