A PILOT SAFETY STUDY OF CAPECITABINE, A NEW ORAL FLUOROPYRIMIDINE, INPATIENTS WITH ADVANCED NEOPLASTIC DISEASE

5-fluorouracil (5-FU) is still one of the most prescribed cytostatic d rugs, but gastrointestinal toxicity limits its use. Capecitabine, an o rally administered prodrug of 5-FU, is activated by a cascade of three enzymes, resulting in the preferential release of 5-FU at the tumor s ite; it was developed in an attempt to avoid the problem of gastrointe stinal toxicity of fluoropyrimidines. The aim of the present study was to the safety profile of capecitabine at the daily oral dose of 502 m g/m(2), given in two divided doses 12 hr apart for at least 10 days of treatment. In conformity with Italian law, 11 patients (8 females and 3 males) with advanced or metastatic pretreated solid tumors (4 colon -rectum, 3 breast, 2 stomach, 1 ovary 1 lung) were enrolled. Treatment duration ranged from 1.5 to 14 days, Ten of the 11 patients received the planned 10 days of treatment. One patient was discontinued on the second treatment day when he presented with symptoms of intracranial h ypertension with multiple brain metastases documented by CT scan. Toxi city consisted of 1 case of mild edema; no adverse events characterist ic of fluoropyrimidines were recorded. No abnormalities in hematologic , renal, hepatic or electrolyte values were seen. In conclusion, capec itabine, given at this dose and for a relatively short period, proved to be well tolerated. Further investigation is recommended to define t he promising antitumor efficacy documented in many human xenograft mod els in mice.