Protracted venous infusion 5-fluorouracil (5FU) combined with mitomycin C (MMC) has demonstrated significant activity against metastatic colorectal cancer. Owing to potential synergy based upon upregulation of thymidine phosphorylase by MMC, the combination of capecitabine and MMC may improve outcomes in irinotecan-refractory disease. Eligible patients with progressive disease during or within 6 months of second-line chemotherapy were treated with capecitabine (1250 mg m À2 twice daily) days 1-14 every 3 weeks and MMC (7 mg m À2 IV bolus) once every 6 weeks. A total of 36 patients were recruited, with a median age of 64 years (range 40 -77), and 23 patients (78%) were performance status 0 -1. The objective response rate was 15.2%. In all, 48.5% of patients had stable disease. Median failure-free survival was 5.4 months (95% CI 4.6 -6.2). Median overall survival was 9.3 months (95% CI: 6.9 -11.7). Grade 3 toxicities were palmar-plantar erythema 16.7%, vomiting 8.3%, diarrhoea 2.8%, anaemia 8.3%, and neutropenia 2.8%. No patients developed haemolytic uraemic syndrome. Symptomatic improvement occurred for pain, bowel symptoms, and dyspnoea. Capecitabine in combination with MMC is an effective regimen for metastatic colorectal cancer resistant to 5FU and irinotecan with an acceptable toxicity profile and a convenient administration schedule.

Gastric cancer is one of the commonest cancers worldwide and is associated with a poor prognosis. Surgery remains the only potentially curative treatment, but is associated with a high rate of locoregional recurrence. Hence, there is ongoing debate regarding both the extent of lymph node dissection and the role of perioperative chemotherapy or chemoradiation for localized disease. Untreated metastatic gastric cancer is associated with a median survival of only 3-4 months, but this can be increased to 8-10 months, associated with improved quality of life, with combination chemotherapy. Currently, no standard combination chemotherapy regimen exists, although regimens utilizing both cisplatin and 5-fluorouracil, such as epirubicin/cisplatin/fluorouracil (ECF), are amongst the most active. Newer chemotherapeutic agents, including irinotecan, oxaliplatin and taxanes, show promising activity, and are currently being tested in phase III trials.

GLMLE appears to be a well-tolerated compound in this setting. There appears to be no objective benefit. However, grade 3/4 hepatic toxicity noted in two patients is of concern and should be considered while evaluating patients taking GLMLE or while designing studies with this agent.

For most patients, the decision to continue on irinotecan beyond 24 weeks is influenced by disease progression or treatment-related toxicity. However, for 17% of patients in whom this decision is clinically relevant, there seems to be little benefit from continuing irinotecan, though the drug was well tolerated without any deterioration in quality of life.