Capecitabine: fixed daily dose and continuous (noncyclic) dosing schedule.
BACKGROUND
Oral fluoropyrimidines are presumed to emulate a parenteral continuous low-dose infusion delivery of the drug and the commonly used schedule is a 14 day on, 7 day off cycle at a total daily dose of 2500 mg/m2 dose. There is a substantial incidence of diarrhea and hand/foot syndrome with this dose schedule.


OBJECTIVE
To retrospectively analyze a clinical experience with a fixed-unit daily dose of capecitabine employed continuously (open ended without cycling) as a single agent, in combination with other agents, or combined with radiation to determine the drug tolerability with regard to stomatitis, diarrhea, and hand/foot syndrome, compared with the "standard" dose schedule.


METHODS
Fifty patients received 58 courses of continuous fixed daily dose capecitabine as a single agent (19 courses), combination with weekly irinotecan (15 courses); combined with 24-hour 5-fluorouracil (5-FU) infusion weekly (5 courses), combined with radiation (3 courses), or with other chemotherapy (16 courses). A fixed divided daily dose of 1500 or 2000 mg was administered for an open-ended period of time designed to deliver 10 weeks of continuous administration. Incidence and time to adverse event (toxicity) was determined for each course.


RESULTS
Capecitabine was administered continuously for 4 weeks to 8 months with a median of 3 months. Seven of 50 patients (14%) experienced grade 2 or 3 toxicity; hand/foot syndrome, 4 (8%); stomatitis plus diarrhea (grade 2), 1%; and diarrhea alone, 3 (6%). Four of the 7 patients developing toxicity received concomitant weekly 24-hour 5-FU and 3 patients received concomitant CPT 11 (1), doxil (1), or taxane (1). None of the patients on single-agent capecitabine (19) developed toxicity of any grade. The total daily dose of capecitabine was 830 to 1250 mg/m2. The maximum dose intensity of the continuous fixed-dose schedule is 8750 mg/m2/week compared with 11,666 mg/m2/week for the standard dose and schedule (2500 mg/m2/day for 14 days every 21 days).


CONCLUSIONS
Capecitabine administered as a continuous daily fixed dose has a low toxicity profile and can be administered in conjunction with other therapies relatively easily. This schedule provides for convenience and simplicity, and therapeutic effects are demonstrated even at low doses. The dose intensity of the noncycling continuous regimen is approximately 20% less than the standard cycling 2 weeks on every 21-day schedule.
Lokich
Jacob
J
The Cancer Center of Boston, Boston, Massachusetts, USA. jlokich@cancercenterofboston.com
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D012189:Retrospective Studies
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil