Annals of Oncology 11: 603-606. 2000.
© 2000 Khmer Academic Publishers. Printed in the Netherlands.
Original article
Cost-analysis of high-dose chemotherapy and peripheral blood
stem-cell support in patients with solid tumors
M. P. Astier, J. I. Mayordomo, J. M. Abad, L. I. Gomez & A. Tres
Division of Medical Oncology, Hospital Clinico Universitario Loiano Blesa', Zaragoza, Spain
euro) (P < 0.001). The distribution of costs shows that wages
and pharmacy account for 72% of total cost. The distribution
Background: The use of High-dose chemotherapy (HDC) with of pharmacy costs per patient shows that chemotherapy (56%
peripheral blood stem cells (PBSC) rescue in the treatment of of pharmacy costs) and antibiotics (26%) account for most of
solid tumors is controversial, and may be an important deter- the cost of medication.
minant of HDC and PBSC use in the future. Until the use of
Conclusions: Our cost estimates agree with those of most
these procedures is proven through disease-free survival and countries with national health insurance programs, and are
overall survival compared with standard-dose chemotherapy, lower than those from the USA. As wages and pharmacy
the associated cost is also under discussion.
account for more than 70% of the costs, the great different
Patients and methods: We evaluate 27 consecutive patients among the costs estimates compared are due essentialy to
with solid tumors who underwent HDC and PBSC rescue, doctors fees or salary and drugs utilization. Anyway, taking
through an accurate review of medical records and cost estimate HDC with PBSC rescue as a model for a therapy that is more
aggressive than standard, and that is associated to a possible
for each patient.
Results: Median age was 45 years. Fifteen had breast survival improvement in indications such as relapsed highcancer, six non-Hodgkin's lymphoma and six other solid tu- grade non-Hodgkin's lymphoma, an adequate cost analysis is
mors. The mean hospital lenght of stay was 21 days and mean crucial both to measure cost-effectiveness and to establish
cost was 21,445 US dollars (21,232 euro). Mean cost was payment to health care providers.
clearly lower for the 9 patients treated within phase III trials,
17,571 US dollars (17,747 euro) than for the remaining 18 Key words: costs, high-dose chemotherapy, peripheral blood
patients, treated in phase I—II trials, 22,747 US dollars (22,975 stem-cell transplantation, solid tumors
Summary
Introduction
Cancer care is becoming more expensive each year.
High-dose chemotherapy (HDC) with autologous bone
marrow transplantation (ABMT) or peripheral blood
stem-cell infusion (PBSC) rescue has been at the forefront
of the controversy about medical costs. This therapy has
been only used in a small percentage of cancer patients.
However, its contribution to direct cancer cost is relatively high, and the pool of potential recipients is large.
In general, when new treatment modalities become
available, the additional financial burden that these
treatments place on the health care system raises concern. Some insurance companies in the USA currently
limit its use claiming that such therapy is 'experimental'
and 'expensive' [1]. However, as the procedure has become
safer [2-4], many patients have received HDC with
ABMT or PBSC.
High-dose chemotherapy with peripheral blood
stem-cell rescue has demonstrated a more rapid neutrophil and platelet engraftment [5-7] with the possibility
of cost-saving compared with ABMT [8]. Once PBSC
is known to be more cost-effective, we evaluate our
experience in HDC with PBSC. The high-dose chemo-
therapy program at our institution has been active for
six years now.
A full accounting of the direct cost of therapy is often
not available from the analysis of the medical records or
hospital database. Inadequate hospital accounting system, incomplete accounting of pre- and posttransplant
periods, and neglect of costs of outpatient, palliative
or supportive care are frequent problems. Since most
previous studies in thisfieldare hampered by potentially
unaccurate estimate of cost based on fixed prices, the
results of this study are based on a comprehensive
review of the medical records, considering the cost of
each procedure and supportive measures involved with
the aim of quantifing the cost in the framework of an
institution belonging to the Spanish National Health
System sofinancedby the budget and health care workers
being civil servants.
Patients and methods
A cost analysis was performed in a sample of 27 consecutive patients
treated in our institution from November 1995 to September 1996. Our
cost analysis was directly collected from hospital patient charts [9].
604
Table 3. Patients'classification.
Table I. Direct cost estimate: unit costs.
Unit cost
(US dollar)"
Items
Unit cost
(Euro)
Type of tumor and trial
Number
Chemotherapy [reference]
of
patients
Hematology test (Hb, Ht, leucocytes,
thrombocytes...)
Biochemistry test (Na, K, creatinine,
glucose...)
Cultures (blood, urine, sputum)
X-ray chest
Computed tomography scan
Ultrasonography
Bone gammagraphy
Subclavian catheter
Platelet transfusion
Red blood cell transfusion
Citotoxic drugs, antibiotics and other
medication
Paclitaxel 30 mg
Carboplatin 50 mg
G-CSF 30
Fluconazole 200 mgs. v.o.
a
0.5
0.5
0.6
17
34
115
26
147
579
188
102
0.6
17
34
116
27
148
585
190
103
153
27
73
8
155
28
73
8
HDC within phase III
Breast cancer, stage II-111
Non-Hodking lymphoma
HDC within phase I—11
SCLC, sarcoma, NPHC,
germ-cell
Breast cancer, stage IV and
ovarian
3
6
CTCb (Antman et al. [10])
CBV (Reece et al. [12])
5
ICE (Fields etal. [13])
CTCb - PTx
(Mayordomo et al. [11])
13
Abbreviations: HDC - high-dose chemotherapy, SCLC - small-cell
lung cancer; NPHC - nasopharingeal cancer.
hospital administrative'databases. Total cost estimates was calculated
for each patient (currency conversion rate, 26 November 1999, 1 US
dollar =1.01 euro).
Currency conversion rate, 26 November 1999: 1 USdollar= 1.01 euro.
Results
Table 2. Indirect treatment costs.
Patient characteristics
Item
Hospital stay (one day)
Intensice care unit stay (one day)
11
Unit cost
(US dollar)"
Unit cost
(Euro)
61
609
62
615
Currency conversion rate, 26 November 1999: I US dollar = 1.01 euro.
Description of the procedures considered under study
Every patient who entered our HDC and PBSC support program in
the target period has been included. This program includes outpatient
medical visits, stem cell mobilization with colony-stimulating factors,
stem cell apheresis and cryopreservation, and admission for high-dose
chemotherapy, and reinfusion.
Estimate of costs
Direct costs
Drugs delivered, diagnostic tests performed, blood products, stem cell
mobilisation, apheresis and reinfusion are the direct costs considered
(Table 1). Unit costs were calculated considering the real use of
resources in each patient. As health care workers received a fixed
salary per month, distribution of wages costs is done considering the
amount of time spent by health care professionals and administrative
staff in the care of these kind of patients. The time has been estimated
by questionnaire to health care workers. In order to reduce variability
in medical practice strict institutional protocols govern the choice and
schedule of administration of drugs and care of support in the HDC
and PBSC programme.
Indirect treatment costs
Overhead hospital costs per day (electricity, meals, cleaning...) and
overhead ICU (Intensive Care Unit) costs per day have been considered
as indirect costs (Table 2). Indirect costs are distributed as percentage
on total hospital overhead costs considering different criteria as square
meters for laboratories, admissions in ICU >earl\ and so on.
The main source of information were patients' medical records and
Three-quarters of patients were women (74%, n = 20)
and one quarter were men (26%, n — 7). Median age was
46 years. Fifteen had breast cancer, six non-Hodgkin's
lymphoma and six other solid tumors. Treatment regimens included cyclophosphamide, thiotepa and carboplatin (CTCb) [10] in 3 patients, CTCb + paclitaxel [11]
in 13 patients, escalated ciclophosphamide, BCNU and
VP16 (CBV) [12] in 6 patients and ifosfamide, ciclophosphamide and VP16 (ICE) in 5 patients (Table 3).
Main outcomes
The median hospital lenght of stay was 21 days (range
14-46). As expected mortality was higher for patients
treated within phase I—II trials: Five patients required
admission in the ICU and three died during aplasia.
Only 1 patient in a phase III trial had a secondary graft
failured and died 60 days post-PBSC infusion. Currently,
20 patients are alive for 25-35 months from HDC and
PBSC rescue.
Cost analysis
Mean cost was 21,445 US dollars (21,232 euro). Mean
cost was clearly lower for the 9 patients treated within
phase III trials, 17,571 US dollars (17,747 euro) than for
the remaining 18 patients, treated in phase I—II trials,
22,747 US dollars (22,975 euro) (P < 0.001) (Table 4).
The distribution of costs per categories (Table 5) shows
that wages and pharmacy account for 72% of the total
cost.
The distribution of pharmacy cost per patient shows
that chemotherapy (56%) and antibiotics (26%) comprised 82% of the cost (Table 6).
605
Table 4. Therapy cost per type of trial.
Mean cost
Standard deviation
Minimum
Maximun
Table 7. Ten most expensive drugs.
HDC phase III
trial (S)
HDC phase I- II
trial (S)
(-test
Drugs
Mean cost per patient
treated
Percentage pharmacy
cost
17,571
6,291
12.870
33,184
22.747
7,600
12,013
37.917
P< 0.001
Pachtaxel
Carboplatin
MESNA
Imipenen cilastatina
5,067
1,163
721
766
28
11
9
Abbreviation: HDC -- high-dose chemotherapy.
Conversion rate. 26 November 1999: 1 S(l US dollar) = 1.01 euro.
TabieS. Distribution of costs.
Variable
Mean
(US dollar)
Wages
Pharmacy
Mobilization
Blood bank
Overhead hospital costs
Diagnostic Test
Hickman catheter
Consultations
8,806
8,417
1,711
1,673
1,316
732
548
66
Total
24,999
Percentage of
total cost
37
35
7
7
6
3
2
0.2
100
Conversion rate. 26 November 1999: 1 S(l US dollar) = 1.01 euro.
Table 6. Distribution of pharmacy cost.
Variable
Chemotherapy
Antibiotics
Colony-stimulating factors
Parenteral nutrition
Others
Total
riuiondzoie
Teicoplanine
Parenteral nutrition
G-CSF
Granisetron
GM-CSF
1
501
533
393
343
338
6
5
4
4
3
Total
85
Table 8. Comparing ; cost estimates.
Author, year
No.
of
pts
Stem-cell
source
Methods
Cost estimate
(S)
Brice Petal.. 1994
16
PBSC
DCE medical
records
24,648
KnechtliCJCetal.,
1994
7
PBSC
DCE medical
records
18,310
Uyl de Groot CA et
al., 1994
26
PBSC
DCE medical
records
17.606
Julia A etal., 1994
10
PBSC
DCE medical
records
10,330
MeisenbergBRet
al., 1998
20" PBSC
DCE medical
records
39,703
Astier Petal., 1996
27
DCE medical
records
21,445
Percentage of total cost
56
26
7
5
5
100
The 10 most expensive drugs (percentage of total
pharmacy cost) were paclitaxel (28%), carboplatin (11%),
esna (9%), imipenem (8%), fluoconazole (7%), teicoplanin (6%), total parenteral nutrition (5%), G-CSF (5%),
granisetron (4%) and GM-CSF (3%) (Table 7).
Even though the three most expensive drugs were
cytotoxic drugs (48%), three antibiotics also represented
a sizable cost (20%) and colony-stimulating factors only
represent 7% of the total pharmacy cost.
8
JJU
PBSC
Abbreviation: DCE - direct cost estimate through medical records
review.
Conversion rate, 26 November 1999: 1 S(l US dollar) = 1.01 euro.
a
Only patients receiving intensive therapy as inpatients are accounted.
in each study to be able to compare results. In this
respect, it is remarkable the variability among previous
reports measuring cost. Some studies mix data from
multiple institutions, thus introducing a high and confounding variability in medical practice. That is why our
study is based on a simple institution to reduce variability.
This study aims to directly estimate the cost of HDC
per patient taking into account the detailed costs of all
procedures performed and drugs delivered to a patient
since admission in a HDC program, including outDiscussion
patient and inpatient care as stem-cell mobilization,
When comparing our study with others, our results are apheresis, HDC, PBSC reinfusion and aplasia-related
very similar to those obtained in France [14], Great costs (including ICU, and readmission to hospital due to
Britain [4], The Netherlands [15], and Spain [16] but comorbidities related with the studied procedure) taking
lower than American data [17] (Table 8). Wages and into consideration the conclusions of recent task forces
pharmacy are the most important costs in this study but from Canada [20] and European Union [21]. We conclude
it is consistent with other studies [14, 18, 19]. We feel that an accurate direct estimate of cost of high-dose
there is a need to standardize which costs are to be chemotherapy is feasible and useful. Nevertheless, it
measured, and consider the different financing systems takes too much effort.
606
The superiority of high-dose chemotherapy over
standard chemotherapy are under discusion for most
solid tumors except for relapsed high-grade non-Hodgkin's lymphoma (NHL). The intensive controversy about
the role of HDC + PBSC in breast cancer is a good
example. Anyway, taking HDC as a model of a therapy,
that is more aggressive than standard, associated to a
possible survival improvement, an adequate analysis of
the costs of therapy in these patients is very important,
both to accurately measure cost-effectiveness and to
establish payments to health care providers.
11.
12.
13.
14.
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Received 13 December 1999; accepted 9 March 2000.
Correspondence to:
M. P. Astier, MD
San Juan Bosco 11, 2B
31007 Pamplona
Spain
E-mail: pilar.astier.pena(a cfnavarra.es