|Benefits of granulocyte-colony-stimulating factor after stem cell transfusion in intensive sequential chemotherapy for breast cancer
|Viens P, Genre D, Protiere C, Gravis G, Bertucci F, Cowen D, Camerlo J, Chabannon C, Novakovitch G, Conte M, Finaud M, Moatti J, Maraninchi D
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.
Granulocyte colony stimulating factor (filgrastim) 5 microgram/kg/day, alone or in combination with peripheral blood stem cells (PBSC), after intensive chemotherapy in patients with poor risk breast cancer.
Economic study type
Women who were at least 18 years of age and with histologically proven breast cancer with more than three involved homolateral axillary lymph nodes, a good Karnofsky performance status and normal haematologic, renal, hepatic and cardiac function.
Secondary care. The economic study was carried out in France.
Dates to which data relate
Effectiveness data were collected between August 1993 and July 1996. 1996 prices were used.
Source of effectiveness data
The evidence for final outcomes was derived from a single study.
Link between effectiveness and cost data
The costing was undertaken prospectively on the same patient sample as that used in the effectiveness study.
47 women were enrolled in the study of whom 46 received four cycles of chemotherapy and were included in the study. One patient decided to stop treatment after two cycles of chemotherapy. 33 patients out of the 46 (72%) received filgrastim after cycle 4 (control group) and 13 (28%) were in the experimental group not receiving filgrastim. Power calculations were not used to determine sample size.
This was a non-randomized controlled trial with historical controls carried out in a single centre. The follow up period appears to have been up to the beginning of the locoregional treatment. Loss to follow was not reported.
Analysis of effectiveness
The analysis of the clinical study was based on intention to treat. The primary health outcomes used in the analysis were: haematological toxicity, non-haematological events and impact on further therapy. There were no significant differences between the two groups of patients in terms of age, hormonal status, TNM stage, or number of involved axillary lymph nodes at diagnosis.
For the control group who received prophylactic filgrastim, the median number of days of filgrastim treatment was 8 (range: 7 - 13). All the patients analysed received stem cell support. The median number of CD34 cells x 106/kg infused for the control group receiving filgrastim was 6.4 (range: 3.2 - 28.5) and 6.9 (range: 3.5 - 12.4) for the group not receiving filgrastim (not significant). The duration of neutropenia of ANC <0.5 x 109/L was significantly shorter in the control group than in the experimental group (1 day versus 6 days), as was the median time to recover an ANC of 0.5 x 109/L, (p<0.05). No difference was found for the median time to recover a platelet count higher than 50 x 109/L. At day 30 after the fourth cycle of chemotherapy there was no difference between the two groups in the values for the ANC. Platelet count values were significantly lower in the control group receiving filgrastim (250 x 109/L versus 337 x 109/L), (p=0.048). Seven patients (21%) in the control group treated with filgrastim received packed red cell transfusions versus five patients (38%) in the group not treated with filgrastim. A high rate of rehospitalisations (61%) was required for toxicity after administration of the fourth treatment in the group not receiving filgrastim compared with 36% in the group treated with filgrastim, but there was no statistically significant difference between the two groups. The median duration of stay in hospital for toxicity was shorter for the patients who received filgrastim than for the other group of patients but the difference was not statistically significant (0 day versus 4 days). The duration of intravenous antibiotics administration was shorter for the control group treated with filgrastim compared with the experimental group not receiving filgrastim. This difference was statistically significant (p=0.02). The delay between beginning another treatment and the last cycle of chemotherapy was not statistically longer in one group than in the other (37 days versus 43 days, for the filgrastim-treated and non-treated groups, respectively).
Filgrastim can decrease the duration of grade IV neutropenia in patients receiving intensive sequential chemotherapy. However, this reduction of neutropenia did not have any impact on further therapy.
Measure of benefits used in the economic analysis
No summary benefit measure was identified in the economic analysis and only separate outcomes were reported.
Quantities and costs were reported separately. The estimation of quantities and of costs was based on actual data. Direct medical costs were estimated by measuring the physical quantities of capital and labour consumed by each patient. Monetary values were assigned to these quantities on the basis of average 1996 prices in French francs. Costs were estimated from day 1 of cycle 4 (included) to the beginning of the locoregional treatment (not included). For pharmacy costs the exact quantities needed by each patient were noted in the patients medical record. For laboratory tests the authors used a national publication of costs. Hospitalisation costs were based on the daily cost of hospitalisation in the medical oncology unit and in the outpatient clinic of the study centre. Costs were not discounted as they were incurred in a short period of time (less than one year).
Statistical analysis of costs
Costs were analysed statistically, although the tests were not explicitly stated.
French francs (Ffr); a conversion to US dollars ($) was performed but the exchange rate used was not quoted.
No sensitivity analysis was carried out.
Estimated benefits used in the economic analysis
The average global cost of the fourth cycle for control patients receiving filgrastim ($3,750 +/- 881) was slightly higher than the cost observed for patients not receiving filgrastim ($3,220 +/- 1,402), but this difference was not statistically significant. Patients not receiving filgrastim incurred higher 'other drug' costs ($180 versus $55) and higher hospitalisation costs ($2,727 versus $2,058). The mean costs of filgrastim was $1,426 (+/- 228).
Synthesis of costs and benefits
The study suggested that the administration of filgrastim (5 microg/kg/day) permitted a faster haematological recovery, with a lower cost to achieve this recovery, particularly in terms of ANC.
CRD COMMENTARY - Selection of comparators
The reason for the choice of comparator is clear:
Validity of estimate of measure of benefit
As no power calculations were used to determine sample size, and this was a small non-randomized study, the effectiveness findings may not be valid.
Validity of estimate of costs
Some resource quantities were reported separately from prices. Adequate details of quantity/cost estimation were given. Cost results may not be generalisable to other settings or countries.
Appropriate comparisons were made with other studies.
Implications of the study
As stated by the authors, a larger randomized trial is needed to assess the cost-effectiveness of filgrastim after PBSC infusion.
Viens P, Genre D, Protiere C, Gravis G, Bertucci F, Cowen D, Camerlo J, Chabannon C, Novakovitch G, Conte M, Finaud M, Moatti J, Maraninchi D. Benefits of granulocyte-colony-stimulating factor after stem cell transfusion in intensive sequential chemotherapy for breast cancer. European Cytokine Network 1998; 9(1): 93-98
Subject indexing assigned by NLM
Adult; Blood Transfusion /economics; Breast Neoplasms /economics /therapy; Combined Modality Therapy; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Filgrastim; Granulocyte Colony-Stimulating Factor /adverse effects /economics /therapeutic use; Health Care Costs; Hematologic Diseases /chemically induced; Hematopoietic Stem Cell Transplantation /economics; Humans; Middle Aged; Patient Readmission /economics; Recombinant Proteins; Treatment Outcome
Date bibliographic record published
Date abstract record published