Biological Activity and Side Effects

Both 5-fluorouracil and cytosine arabinoside remain widely used in combination cancer chemotherapy. 5-Fluorouracil is one of the most effective drugs against colon cancer (311).Cytosine arabinoside is effective in leu-kemias and lymphomas but has a very short half-life (ca. 12 min in man), because of catab-olism by cytidine deaminase (321), and various non-specific prodrug forms are used (322). Gemcitabine was shown in phase I trials to be active in a number of cancers, especially in non-small-cell lung cancer, where it showed >20% responses as a single agent and up to 54% in combination with cisplatin (323). In phase II trials, it has proved active in a wide range of tumors, including non-small-cell lung cancer (>60% responses in combination with cisplatin) (324), urothelial (22-28% responses as monotherapy, 42-66% in combination with cisplatin) (325), advanced breast cancer (25.0%responses as monotherapy) (326), and metastatic bladder cancer 42-66% responses in combination with cisplatin) (327).The main adverse effects were hematological but were generally mild. A number of large phase III trials are in progress.

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