Raltitrexed treatment promotes systemic inflammatory reaction in patients with colorectal carcinoma

We studied longitudinally inflammatory reactions and serum C-reactive protein (S-CRP) levels in 52 colorectal cancer patients treated with a median of six 3-weekly cycles of raltitrexed 1.5-3.0 mg m(-2) combined with oral carmofur (1-hexylcarbomoyl-5-fluorouracil) 300-400 mg m(-2) on cycle days 2-14. Thirty-nine (75%) of these patients had fever on days 2 to 9 after receiving raltitrexed, 49 (94%) had fatigue Gr. > or = 1, and 49 (94%) elevated S-CRP without a documented infection. The systemic inflammatory composite score (consists of body temperature, fatigue, S-CRP, interleukin-6 (S-IL-6), S-IL-8, and tumour necrosis factor-alpha (S-TNF alpha) levels) was calculated in a cross-sectional one-cycle study involving 60 colorectal cancer patients treated with single-agent raltitrexed, raltitrexed and carmofur, or 5-fluorouracil-based chemotherapy (n=20 in each group). The median S-CRP, S-IL-6, and S-TNF alpha levels were higher 7 days after giving raltitrexed (57 vs 23 mg l(-1), 64 vs 10 ng l(-1), and 11 vs 10 ng l(-1), respectively) or raltitrexed+carmofur (142 vs 10 mg l(-1), 64 vs 10 ng l(-1), and 16 vs 9 ng l(-1), respectively) than at baseline (P<0.01 for each comparison), but not when 5-fluorouracil-based regimens were administered. These findings suggest that colorectal cancer patients treated with raltitrexed may develop drug-related systemic inflammation, which may be difficult to discriminate from infection.