Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study

The aim of this study was to define the maximum tolerated dose (MTD) of bolus mitomycin C (MMC) in combination with 24 h-continuous infusion of 5-flourouracil (FU) plus folinic acid, and to assess the toxicity and activity in patients with previously treated colorectal and gastric cancer. Escalating doses of MMC starting from 6 mg m(−2) in 2 mg m(−2)-steps to a maximum of 10 mg m(−2) were applied on days 1 and 22, given to fixed doses of 5-FU (2.600 mg m(−2)) as 24 h infusion and folinic acid 500 mg m(−2) prior to 5-FU weekly for 6 weeks. At least three patients were treated at each dose level. A total of 16 patients have been included in the phase I study. At the highest dose level (MMC 10 mg m(−2)), grade III thrombocytopenia, dyspnoea, mucositis and diarrhoea were observed in one patient each (17 %). In the phase II study 45 patients, 33 with colorectal cancer and 12 with gastric cancer, 23 patients after failure of first- and 22 patients after at least second-line or subsequent chemotherapy have been treated. Seven partial responses (PR) were registered (16%), one (3%; CI(95%), 0–16) in colorectal and six (50%; CI(95%), 21–79%) in gastric cancer patients. In all, 17 (38%) achieved disease stabilisation, 15 colorectal (45%, CI(95%), 28–64%) and two gastric cancer patients (17%; CI(95%), 2–48%). The median progression-free survival was 3.1 months (range, 0.9–9.1) in colorectal and 4.6 months (range, 0.7–12.4) in gastric cancer. The median overall survival time was 6.6 months (range, 1.9–15.6) in colorectal and 7.1 months (range, 1.7–20.8) in patients with gastric cancer. This regimen was considered to be safe and well tolerated for pretreated patients with gastrointestinal adenocarcinoma. In gastric cancer,MMC plus infusional 5-FU/folinic acid may be a potential second-line regimen with promising antitumour activity.