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Advanced colorectal carcinoma: redefining the role of oral ftorafur |
Ron I G, Lotan A, Inbar M J, Chaitchik S |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Oral ftorafur, an in-vivo pro-drug (tetrahydro-2-furanyl derivative of 5-fluorouracil) and a known antineoplastic agent in colorectal cancer.
Economic study type Cost-effectiveness and cost-utility analyses.
Study population The study population comprised elderly patients who had undergone resection of histologically confirmed adenocarcinoma of the large bowel and rectum, who had not yet given chemotherapy but who had an observed extension of the disease (staging at Dukes B2-D).
Setting Home care and hospital. The economic study was carried out in Tel Aviv, Israel.
Dates to which data relate Effectiveness and resource use data were collected during the period February 1991 to November 1992. The price year was not stated
Source of effectiveness data Effectiveness data were derived from a single study.
Link between effectiveness and cost data The costing was undertaken retrospectively on the same patient sample as that used in the effectiveness study.
Study sample 61 patients were enrolled, 35 in the ftorafur and leucovorin orally at home group and 26 in the 5-FU and leucovorin intravenously (IV) in clinic group. Sample size was not determined by power calculations.
Study design This study was a nonrandomized trial with concurrent controls in a single centre. Consecutively presenting patients were non-randomly divided into two groups on the basis of Karnofsky performance status (KPS) as assigned by the treating physician and symptomatically. Patients underwent routine blood tests at 6 week intervals and radiological assessment every three months. The mean duration of treatment in the ftorafur and leucovorin group was 6.4 months (range 2-18 months) and for the 5-FU and leucovorin group was 7.2 months (range 2-18 months). No patients were lost to follow-up.
Analysis of effectiveness The analysis of the clinical study was based on intention to treat. The primary health outcomes used in the analysis were objective response (using standard WHO criteria), clinical response (KPS improved) and length of survival. The ftorafur and leucovorin group consisted of patients who were symptomatic, had low KPS scores and more advanced disease. Group B consisted of patients with a higher KPS score and less advanced disease.
Effectiveness results The oral ftorafur and leucovorin group had a better, albeit not statistically significant, objective response rate than the iv 5-FU with leucovorin group (30% versus 20.8%). Subjective assessment of response (improved KPS) was seen in 57.1% of the home-treated ftorafur group and 50.3% of the clinic based 5-FU and leucovorin group. The differences in terms of mean change of KPS between groups favoured the ftorafur and leucovorin combination. The mean survival time of the ftorafur group was 10.61 months with a median time of 8 months; for the 5-FU group the mean survival was 14.87 months with a median of 9 months. Survival analysis did not show "significant differences" between groups. During 24 months of treatment, 16 patients (45.7%) from the ftorafur group and 7 patients (26.9%) from the 5-FU group had no side effects. Nine patients (34.6%) on 5-FU suffered grade 3 and 4 side effects as compared to 3 patients (8.6%) on oral ftorafur.
Clinical conclusions The study results suggest some survival advantage conferred either by the oral treatment or the home setting, given that the home-treated group was generally at a later stage of disease and with lower KPS, and therefore, might have been expected to manifest a significantly shortened survival time.
Modelling Survival was estimated using the Kaplan-Meier life table method.
Measure of benefits used in the economic analysis Improvement in quality of life, major side effects avoided, additional toxin free patients.
Direct costs Some quantities of resource use were reported separately. The costs of one month's treatment for in-patient and out-patient schedules were calculated using figures from one hospital and one pharmaceutical supplier. The costs of home nurse's time were estimated as were the hospital-day and drug costs. The price year was not clearly reported.
Currency US dollars ($) (conversion from shekels: US$1.00=3.00 shekels).
Sensitivity analysis No sensitivity analysis was performed.
Estimated benefits used in the economic analysis The mean changes in the KPS for the ftorafur option were +14.53 at 3 months and +20.00 at 6 months. The corresponding figures for the 5-FU option were -6.87 (3 months, p=0.01) and -14.41 (6 months, p<0.001). During 24 months of treatment, 16 patients (45.7%) from the ftorafur group and 7 patients (26.9%) from the 5-FU group had no side effects. Nine patients (34.6%) on 5-FU suffered grade 3 and 4 side effects as compared to 3 patients (8.6%) on oral ftorafur.
Cost results For one month of treatment the home care protocol cost $606 ($56 for ftorafur, $116 for leucovorin and $433 for the home nurse service) and the clinical care protocol cost $2,203 ($15 for 5-FU, $21 for leucovorin and $2166 for clinic services). Estimates of savings to patients and their families were not attempted. The ratio of costs of home to hospital care were 1:3.6, or a difference of 70% favouring home care.
Synthesis of costs and benefits Since the home-care ftorafur option (the intervention) turned out to be dominant, the costs and benefits were not combined.
Authors' conclusions This study suggests that home-based care for patients with advanced colorectal carcinoma using orally administered ftorafur and leucovorin is at least as effective as, and much less costly than, the current standard IV therapy (5-FU and leucovorin) in terms of providing significant anti-tumour effect, palliation, ease of administration and relatively few side effects. A home treatment programme based on oral ftorafur may be the most desirable option for all patients with advanced colorectal carcinoma.
CRD COMMENTARY - Selection of comparators The reason for the choice of comparators is clear.
Validity of estimate of measure of benefit The estimate of the measure of benefit used in the economic analysis was based on a nonrandomized trial using concurrent controls, with small patient numbers in a single centre. As the authors suggested, confirmation of their findings by other studies is required in order to determine whether their results are valid.
Validity of estimate of costs Most resource use quantities were not reported separately from prices and inadequate details of quantity and cost estimation were given. Important cost elements such as productivity losses and travel costs were omitted from the analysis.
Other issues The authors' general conclusions were justified, given the uncertainties in the data. The issue of generalisability to other countries was not addressed.
Bibliographic details Ron I G, Lotan A, Inbar M J, Chaitchik S. Advanced colorectal carcinoma: redefining the role of oral ftorafur. Anti-Cancer Drugs 1996; 7(6): 649-654 Indexing Status Subject indexing assigned by NLM MeSH Adenocarcinoma /drug therapy /economics; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic /administration & Antineoplastic Combined Chemotherapy Protocols /adverse effects /economics /therapeutic use; Colorectal Neoplasms /drug therapy /economics; Female; Fluorouracil /administration & Home Nursing /economics; Humans; Karnofsky Performance Status; Leucovorin /administration & Male; Middle Aged; Quality of Life; Tegafur /administration & dosage; dosage /economics; dosage /economics; dosage /economics AccessionNumber 21997006533 Date bibliographic record published 31/10/1998 Date abstract record published 31/10/1998 |
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