This study was designed to compare the impact of uracil/tegafur (in a molar ratio of 4:1 [UFT]) plus oral calcium folinate (Orzel) vs 5-fluorouracil (5-FU) plus oral calcium folinate(Drug information on calcium folinate) on the utilization of selected inpatient and outpatient services, as well the indirect impact of illness (as measured by extra care and work-loss due to illness) in patients with metastatic colorectal cancer. Data on resource utilization and indirect impacts of illness were collected in conjunction with a multinational phase III clinical trial of UFT plus oral calcium folinate vs 5-FU plus oral calcium folinate in metastatic colorectal cancer (Protocol CA146-012).
Inpatient measures of interest included hospitalizations for febrile neutropenia, documented infection, tumor progression, study drug toxicity, transfusion, and other or unknown reasons. Corresponding numbers of days in hospital also were tracked. Hospitalizations for chemotherapy administration were excluded from all analyses as this information was not systematically collected. Admissions to intensive care units and nursing homes also were documented for each study subject. Outpatient services included hospital, family doctor, private nurse, physiotherapist, and home-help visits. Measures of the indirect impact of illness included the number of hours per day that subjects required extra physical care from family and/or friends, as well as days of work missed due to illness.
Study measures were tallied for all treated subjects in Protocol CA146-012 and contrasted between those who received UFT plus oral calcium folinate vs 5-FU plus oral calcium folinate. Formal hypothesis testing was not undertaken, as the study was not adequately powered to detect potentially important differences between treatment groups in the measures of interest.
A total of 373 subjects (188 patients receiving UFT plus oral calcium folinate and 185 patients receiving 5-FU plus oral calcium folinate) were included in this evaluation. Approximately one-third of the subjects were hospitalized between randomization and the end of the treatment phase. The total number of hospitalizations was higher among patients receiving 5-FU plus oral calcium folinate (86 patients vs 70 patients receiving UFT plus oral calcium folinate), as was the number of days in hospital (726 days vs 595 days for patients receiving UFT plus oral calcium folinate). Although only four patients were admitted to the intensive care unit, all of these admissions were among patients in the 5-FU/oral calcium folinate group, accounting for 18 days in intensive care. The frequency of nursing home admissions was low in both groups. No discernible differences in the use of outpatient services were observed between treatment groups.
Among patients who were employed at baseline (~ 25% of the study cohort), a higher percentage of those receiving 5-FU plus oral calcium folinate missed work because of illness (90% vs 80% of patients receiving UFT plus oral calcium folinate). The mean number of days of work loss due to illness was also higher among these patients (58 days vs 45 days in the UFT plus oral calcium folinate group).
Our findings suggest that UFT plus oral calcium folinate therapy may be associated with reductions in the use of inpatient services among patients with metastatic colorectal cancer. These results should be considered conservative, as we did not include hospitalizations for chemotherapy administration, which would likely be more frequent among patients receiving 5-FU. Use of UFT plus oral calcium folinate also appears to be associated with substantially less work loss due to illness.