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discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/7129994

Cost-minimization analysis for Portugal of five

doublet chemotherapy regimens from two
phase III trials in the treatment of advanced
non-small cell lung cancer
Article in Lung Cancer July 2006
DOI: 10.1016/j.lungcan.2006.03.005 Source: PubMed

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Lung Cancer (2006) 52, 365371

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journal homepage: www.elsevier.com/locate/lungcan

Cost-minimization analysis for Portugal of ve

doublet chemotherapy regimens from two
phase III trials in the treatment of advanced
non-small cell lung cancer
F.L. Pimentel a,,1, S. Bhalla b, L. Laranjeira c, M. Guerreiro c
a

Hospital S
ao Sebasti
ao, Oncology Department, R. Dr. C
andido Pinho, 4520-211
Santa Maria da Feira, Portugal
b
Eli Lilly and Company, Lilly House, Priestly Road, Baskingstoke, Hampshire, RG24 9NL, UK
c
Lilly Portugal Produtos Farmac
euticos, Portugal, R. Dr. Ant
onio Loureiro Borges, Edifcio 1-Piso 1, Arquiparque-Miraores,
1499-016 Alg
es, Portugal
Received 23 January 2006 ; received in revised form 8 March 2006; accepted 10 March 2006

KEYWORDS
Cisplatin;
Cost-minimization;
Gemcitabine;
Non-small cell lung
cancer

Summary
Objectives: Economic evaluations of chemotherapy regimens for stage IIIB or IV non-small cell
lung cancer (NSCLC) have been conducted for many European countries, but not for Portugal.
This study evaluates the total health care costs of ve commonly used doublet regimens with
similar efcacy results.
Methods: Using the methodology reported by Schiller [Schiller JH, Tilden D, Aristides M, Lees
M, Kielhorn A, Maniadakis N, et al. Restropective cost analysis of gemcitabine in combination with cisplatin in non-small cell lung cancer compared to other combination therapies in
Europe. Lung Cancer 2004;43:10112], we conducted a cost-minimization analysis to compare vinorelbine-cisplatin (Vin/Cis), gemcitabine-cisplatin (Gem/Cis), paclitaxel-carboplatin
(Pac/Carb), docetaxel-cisplatin (Doc/Cis), and paclitaxel-cisplatin (Pac/Cis). The perspective
was that of the Portuguese National Health Service and included only direct medical costs
(reimbursed costs plus co-payments): chemotherapy acquisition, chemotherapy administration,
hospitalizations due to adverse events, and other medical resources. Unit costs were drawn
from ofcial sources (Diagnosis Related Groups and retail/hospital costs) (2003 value [Diagnosis
Related Groups (DRG) published at Di
ario da Rep
ublica; 2003]). Resource use was estimated
from two multicenter randomized phase III trials [Comella P, Frasci G, Panza N, Manzione L, De
Cataldis G, Ciof R, et al. Randomized trial comparing cisplatin, gemcitabine, and vinorelbine
with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell

Corresponding author. Tel.: +351 256 379700; fax: +351 256 373867.
E-mail address: fpimentel@cs.ua.pt (F.L. Pimentel).
Associated Professor in SACS Aveiro University, Head of Oncology Department of Hospital S
ao Sebasti
ao.

0169-5002/$ see front matter 2006 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.lungcan.2006.03.005

366

F.L. Pimentel et al.

lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group.
J Clin Oncol 2000;18:14517; Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook
J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.
N Engl J Med 2002;346:928]. A time horizon of a full course of therapy was adopted. One-way
sensitivity analyses were performed.
Results: The least and the most costly chemotherapy regimens were Gem/Cis and Pac/Carb,
respectively. Total mean cost per patient was estimated at D 7083 for Gem/Cis and D 10,008 for
Pac/Carb, a mean cost savings of D 2925 per patient for Gem/Cis. The differences were mainly
due to the higher chemotherapy acquisition costs of Pac/Carb than for Gem/Cis. Gem/Cis was
less costly in all sensitivity analyses except when 100% inpatient chemotherapy administration
was assumed.
Conclusion: Gem/Cis should be considered as a cost-saving alternative to the other four regimens
in treating NSCLC patients in Portugal.
2006 Elsevier Ireland Ltd. All rights reserved.

1. Introduction
Cancer is an important cause of morbidity and the second
leading cause of death in Portugal [1]. Worldwide, nonsmall cell lung cancer (NSCLC) is a leading cause of cancerrelated mortality. Over the past years, there has been slow
but steady progress in the treatment options of NSCLC.
Chemotherapy has achieved modest improvements in survival and quality of life. New diagnostic tools and the use
of novel drugs such as gemcitabine, vinorelbine, and the
taxanes have markedly changed the treatment options for
NSCLC over recent years.
Because of increases in health care costs, however, the
economic value of the various treatments has been under
considerable scrutiny. Rising health care costs, expensive
new health care technologies, and increasing patient expectations are placing huge pressures on health care systems.
As a result, decision makers need more information on the
relative cost of new therapies and treatments in addition to
their clinical benets. Portugal lacks robust data regarding
the economics of lung cancer. Pharmacoeconomics assumes
an ever increasing importance as changes in health care systems occur in response to market forces for improved cost
control, regulatory initiatives on cost and quality, and consumer demands for quality care and greater exibility in
provider choice.
Chemotherapy is supported by the national health care
service in Portugal for the treatment of cancer, so it is
important to evaluate the impact of different regimens with
respect to health care expenditures. Such information could
better equip health care decision makers not only to choose
the most cost-efcient regimen, but also to improve health
care policies and decisions.
Two recent multicenter randomized phase III trials
(Comella et al. [2]; Schiller et al. [3]) demonstrated
that ve platinum-based doublets with novel agents were
comparable in terms of efcacy in the treatment of
advanced NSCLC. A retrospective cost analysis of these
two studies provided an economic rationale for the use of
gemcitabine-cisplatin (Gem/Cis) as a rst-line treatment
option in ve European countries for patients with NSCLC,
as compared to vinorelbine-cisplatin (Vin/Cis), paclitaxelcarboplatin (Pac/Carb), docetaxel-cisplatin (Doc/Cis), and
paclitaxel-cisplatin (Pac/Cis) [4].
Economic evaluations of chemotherapy regimens for
advanced NSCLC have been conducted for many European

countries, but not for Portugal. The objective of this study

was to compare total cost of treatment associated with ve
novel chemotherapy regimens to determine which would be
the most cost-efcient for stage IIIB or IV NSCLC in Portugal
and to compare our ndings with the previously published
results for France, Germany, Italy, Spain, and the United
Kingdom (UK).

2. Methods
2.1. Economic evaluation
Our economic analysis was conducted from the perspective
of the Portuguese National Health Service and performed
using the time frame of a complete course of chemotherapy. A cost-minimization approach was chosen based on the
clinical data extracted from two comparative randomized
phase III trials [2,3]. These two studies present an economic evaluation in European countries, using the therapeutic regimens more frequently used in Portugal for the
treatment of NSCLC. In these two studies, patients were
randomized to receive one of ve doublet treatments for
stage IIIB or IV NSCLC (Table 1). Regimens used in the
Comella study included Gem/Cis and Vin/Cis. Regimens used
in the Schiller study were Pac/Cis, Gem/Cis, Doc/Cis, and
Pac/Carb. Except for the longer time to progressive disease observed for Gem/Cis compared with that of Pac/Cis
(4.2 months versus 3.4 months) in the Schiller study, there
were no signicant differences found among the efcacy
outcomes in either study.
On the basis of these clinical results, we performed a
cost-minimization analysis to identify which of the abovementioned treatments is the most cost-efcient (i.e., offers
the lowest cost and thus the greatest monetary value) in
Portugal.

2.2. Health resources

Resource-use data obtained (using methodology described
by Schiller et al.) from the two randomized phase III trials
[2,3] provided averages by regimen for chemotherapy doses;
number of doses per cycle; number of cycles per patient;
number of drug administrations; percentage of hospitalized
patients due to adverse events (febrile neutropenia, thrombocytopenia, nausea and vomiting, neuropathy, anemia, and

Cost analysis for Portugal in advanced NSCLC

Table 1

367

Resources utilized
Comella et al. [2]

Schiller et al. [3]

Gem/Cis
(n = 70)

Vin/Cis
(n = 68)

Gem/Cis
(n = 288)

Pac/Carb
(n = 290)

Doc/Cis
(n = 290)

Pac/Cis
(n = 288)

Dose (mg/m2 )
No. of doses by cycle
Cycle length (weeks)
No. of cycles per patient
Outpatients (%)
No. of drug administrations

1000/100
3/1
4
2.6
100
7.8

30/120
5/1
5
2.5
100
12.5

1000/100
3/1
4
3.4
100
10.3

225/AUC 6
1/1
3
3.6
100
3.6

75/75
1/1
3
3.5
100
3.5

135/75
1/1
3
4.0
0
4.0

Hospitalizations due to (%)

Febrile neutropenia
Thrombocy topenia
Nausea and vomiting
Neuropathy
Anemia
IV antibiotics

10.7
30.0
30.0
3.0
1.7
25.0

27.8
20.0
50.0
20.0
3.4
26.5

10.7
30.0
33.0
8.6
1.7
25.0

7.7
2.0
9.0
24.8
1.0
18.3

17.8
1.0
21.0
5.0
2.0
29.0

24.7
2.0
24.0
5.0
1.0
33.8

Other medical resources

Radiotherapy (%)
RBC transfusions (%)
Platelets transfusions (%)
Mean no. hospital visits per patient

23.3
16.0
8.0
11.7

23.3
21.0
8.0
12.2

22.2
16.0
8.0
12.0

23.4
6.0
2.0
13.1

23.4
14.3
6.0
11.1

23.4
14.3
6.0
12.2

intravenous antibiotics); percentage of patients receiving

radiotherapy; percentage of patients receiving red blood
cell and platelet transfusions; mean number of hospital visits per patient (Table 1); and percentage of patients with
need for concomitant medications (includes only medication
administered prior to and after chemotherapy).
In Portugal, patients receiving chemotherapy do not routinely visit the general practitioner. Alternatively, treatment
is generally provided and evaluated by hospital specialists. All regimens are administered in an outpatient setting
except Pac/Cis, for which administration usually requires
24-h hospitalization. Therefore, it was appropriate that the
administration of Pac/Cis be considered entirely on an inpatient basis, while the other four regimens be considered
entirely on an outpatient basis (Table 1).

2.3. Cost estimation

Costs were grouped into the following components: (1)
chemotherapy acquisition (includes cost of novel and platinum agent); (2) chemotherapy administration (includes cost
of inpatient and outpatient chemotherapy administration);
(3) hospitalizations due to adverse events (febrile neutropenia, thrombocytopenia, anemia, nausea and vomiting, neuropathy, events requiring intravenous antibiotics); and (4)
other medical resources (includes costs related to hospital
visits, radiotherapy, transfusions, and concomitant medications).
Total costs included only direct medical costs (reimbursed costs plus co-payments) for each regimen. Neither
indirect costs, such as work absence, nor intangible costs
related to quality of life, such as pain and suffering, were
considered. Unit costs were drawn from ofcial sources
(Diagnosis Related Groups (DRG) [5] and retail/hospital costs

[6,7]), and discounting rates were not applied since the time
horizon did not exceed 1 year. Costs (at year 2003) are presented in euros (D ), and related only to branded drugs. Labs,
diagnostic, or monitoring tests were assumed to be equal
across the doublets, and were not included in the cost comparison.
Chemotherapy acquisition cost was estimated as the drug
cost per cycle multiplied by the average number of cycles
received per patient based on trial data. Total chemotherapy dose and cost were based on an average body surface
area of 1.8 m2 per patient and used the following formula:
sum of all cost components = cost of chemotherapy acquisition + cost of chemotherapy administration + cost of hospitalization + cost of other medical resources. The cost of
chemotherapy administration was calculated by multiplying the number of doses used per cycle by the unit cost
of inpatient or outpatient administration, depending on the
regimen. DRG data was used to estimate the cost of administering platelet transfusions. Cost of hospitalization per
patient was calculated by summing the products obtained
from the percentage of patients hospitalized times the cost
per hospital episode for each type of adverse event. The
costs for other medical resources were estimated by multiplying the expected cost per patient by the number of
patients requiring the intervention. The hospital visit cost
was computed as the average cost of one central hospital
visit and one oncology hospital visit.

2.4. Sensitivity analyses

Sensitivity analyses were conducted by varying the input values of components considered to be cost drivers in Portugal:
chemotherapy acquisition cost, unit cost of hospitalization,
and unit cost of administration. The chemotherapy acquisi-

368

F.L. Pimentel et al.

tion cost of Gem/Cis, as the least costly regimen, was varied

by 10% and by 20% of the number of cycles. The unit costs
for hospitalizations and administration were varied across all
regimens by 20%. These rates were chosen based on the economic evaluation done by Schiller et al. Also conducted was
a sensitivity analysis related to the site of administration
assuming the extreme scenarios of having 100% inpatients
versus 100% outpatients for all ve regimens. Due to the
patterns of chemotherapy administration in Portugal, the
100% inpatients assumption should only affect the results in
the Pac/Cis arm.

3. Results
Fig. 1

3.1. Cost-minimization results

In Portugal, Gem/Cis was associated with the lowest total
mean cost per patient among the ve regimens (Table 2).
The total mean cost of Gem/Cis per patient for Portugal
was estimated to be D 6046 per the Comella data and D 7083
per the Schiller data; the difference was attributable to the
average number of cycles administered. The Pac/Carb regimen was the most costly (Table 2).
Gem/Cis produced a mean cost saving per patient of
D 326 versus Doc/Cis; D 1201 versus Vin/Cis; D 1717 versus
Pac/Cis; and D 2925 versus Pac/Carb. The latter cost saving
occurred mainly due to the higher costs of chemotherapy
associated with Pac/Carb. Indeed, 42% of the total mean
cost for Gem/Cis was associated with chemotherapy acquisition cost versus 70% for Pac/Carb (Fig. 1). Gem/Cis had the
highest proportion of cost associated with hospitalizations
compared with that of the other regimens (except Vin/Cis)
mainly due to a higher incidence of thrombocytopenia and
nausea/vomiting. Despite this, hospitalization costs were
offset by the lower chemotherapy acquisition cost (Fig. 1).
The chemotherapy acquisition cost was the biggest cost
driver for all ve regimens except for Vin/Cis, where hospitalizations were the major driver (Fig. 1). Chemotherapy
administration was the smallest cost driver in the total mean
cost and was similar across all regimens.

Table 2

Cost distribution by component for Portugal.

3.2. Sensitivity analyses

Sensitivity analyses were conducted relative to Gem/Cis
because it was the least costly regimen. Table 3 shows that
Gem/Cis was less costly compared to the other regimens
in all sensitivity analyses scenarios except for Doc/Cis and
Pac/Cis.
When the unit cost of hospitalizations was decreased
by 20%, the incremental cost savings associated with
Gem/Cis ranged from D 462 (versus Doc/Cis) to D 3073 (versus Pac/Carb) (Table 3). When costs associated with hospitalizations was increased by 20%, the incremental cost savings
were less pronounced, ranging from D 190 (versus Doc/Cis)
to D 2777 (versus Pac/Carb).

3.3. Portugal versus other countries

In the Schiller cost-analysis study [4], the Gem/Cis regimen
represented the lowest direct medical costs for patients in
all ve European countries (UK, France, Germany, Italy, and
Spain). This held true for our cost analysis for Portugal, and,
in Portugal as in the other countries, the Pac/Carb combination was associated with the highest total treatment cost

Average total cost per patient for Portugal (D )

Component

Comella et al. [2]

Gem/Cis
(n = 70)

Vin/Cis
(n = 68)

Schiller et al. [3]

Gem/Cis
(n = 288)

Pac/Carb
(n = 290)

Doc/Cis
(n = 290)

Pac/Cis
(n = 288)

Chemotherapy drug acquisition

Chemotherapy administration
Hospitalizationsa

2330
362
2004

2155
580
3071

3065
476
2219

6919
166
1478

4288
163
1541

4642
882
1830

Other medical resources

Hospital visits
Radiotherapy
Blood transfusion
Concomitant medications

1351
295
695
19
342

1442
308
695
22
417

1323
303
660
18
342

1444
330
697
6
412

1418
280
696
16
426

1445
307
697
16
426

Total cost
Incremental cost vs. Gem/Cis

6046

7247
+1201

7083

10008
+2925

7409
+326

8800
+1717

a Hospitalization costs separated by adverse event was not available. GREAT software only provides the aggregated cost for
hospitalizations.

Cost analysis for Portugal in advanced NSCLC

Table 3

369

Sensitivity analysis for Portugal

Change from baseline

Incremental cost, D (Gem/Cis vs. other)

Vin/Cisa (n = 68)

Pac/Carbb (n = 290)

Doc/Cisb (n = 290)

Pac/Cisb (n = 288)

Cost of GEM/CIS
10%
+10%

1425
976

3231
2618

625
26

2015
1418

No. of cycles
20%
+20%

1172
1231

2325
3646

171
497

1336
2085

Unit cost of hospitalization

20%
+20%

988
1414

3073
2777

462
190

1795
1639

Unit cost of administration

20%
+20%

1157
1245

2987
2863

389
263

1636
1798

Administration of chemotherapy
100% inpatient
2014
100% outpatient
1201

1769
2925

+842
326

+59
1021

a
b

Data for Gem/Cis and Vin/Cis from Comella et al.

Data for Gem/Cis and comparator from Schiller et al.

(Table 4). The incremental cost saving per Gem/Cis versus

Pac/Carb varied between D 2668 (Italy) and D 5342 (France).
The cost saving in Portugal (D 2925) was closest to that of
Italy.
In absolute values (D ), Portugal was found to have the
third highest total cost associated with Gem/Cis treatment
after Germany and the UK (Fig. 2). With regard to Pac/Carb,
Portugal was found to have the fourth highest cost after Germany, France, and the UK. Italy and Spain had lower total
costs associated with the treatment of NSCLC independently
of the doublet regimen compared with that found for Portugal.
Analyzing the total cost distribution by each cost component, drug administration in Spain contributed the most
to the total cost associated with Gem/Cis, while hospitalization contributed little (Fig. 3); the reverse situation was found for Portugal. Regarding Pac/Carb, the cost
distribution in Portugal was found to be similar to that

Table 4
Country

Fig. 2 Highest and lowest cost regimen by country (Gem/Cis

from Schiller et al.) [3,4].

Total treatment cost per patient by country (D )

Comella et al. [2]

Schiller et al. [3]

Gem/Cis (n = 70)

Vin/Cis (n = 68)

Gem/Cis (n = 288)

Pac/Carb (n = 290)

Doc/Cis (n = 290)

Pac/Cis (n = 288)

France
Germany
Italy
Spain

5640
6999
5310
4072

7472
8143
6500
4899

6551
8250
5972
5082

11893
12265
8640
9750

7135
8329
8121
6512

8694
11052
8082
6746

UKa

7904
[4968]

9959
[6260]

9642
[6061]

13504
[8488]

10053
[6319]

11259
[7077]

Portugal

6046

7247

7083

10008

7409

8800

1 Sterling = D 1.5909 per annual average Bank of England exchange rate for 2002.

370

F.L. Pimentel et al.

Fig. 3

Cost distribution for each regimen by country (data from Schiller et al.) [3,4].

of Italy, and similar to that of Pac/Cis and Doc/Cis in

Germany.

4. Discussion
Our study, conducted from the perspective of the National
Health Service of Portugal, identied Gem/Cis as a costsaving alternative when compared with other currently used
combination regimens in Portugal, like Vin/Cis, Pac/Carb,
Pac/Cis, and Doc/Cis, with Pac/Carb being the least costefcient regimen.
According to our results, per patient savings due to adopting the Gem/Cis regimen as a rst-line treatment for NSCLC
would range from D 326 (compared to Doc/Cis) to D 2925
(compared to Pac/Carb). These results were submitted to
sensitivity analyses, which conrmed that Gem/Cis offers
the greatest value for money under almost all of the
hypothesized scenarios.
Despite the similarity in efcacy results for the platinumbased doublet regimens in the Comella and Schiller studies,
we hypothesized that variable toxicity proles may lead to
possible differences among the regimens in hospitalization
costs. Our evaluation showed that Gem/Cis was associated

with a higher number of hospitalizations due to toxicity. This

higher level of toxicity was somewhat expected as it was
probably caused by the length of the cycle (28 days) in the
clinical trials that support this paper. It is known that the
higher rate of hospitalization in cycles with cisplatin is due
mainly to a higher incidence of adverse reactions, which can
increase hydroelectrolytic disorders (nausea and vomiting)
and/or renal toxicity [8].
In one of the two base study trials [3], Schiller et al.
showed that Gem/Cis is associated with a longer time to disease progression compared with that of Pac/Cis [4]. Thus,
the approach in the current study can be considered conservative for Gem/Cis in the comparison with Pac/Cis.
Overall, the results and trends in Portugal are consistent with those reported in previous studies performed in
other European countries. The Schiller cost-analysis study
[4] demonstrated that treatment with Gem/Cis was associated with the lowest direct medical costs for patients in all
ve European countries under study (UK, France, Germany,
Italy, and Spain).
Generally, a regimen of chemotherapy is chosen mainly
on the basis of the patients health status in combination
with the clinical evidence reported in the literature, with
the hope of improving the patients survival and/or quality

Cost analysis for Portugal in advanced NSCLC

of life. Platinum-based combination chemotherapy is currently recommended as the standard treatment for patients
with NSCLC, but its benet seems limited to patients with
a performance status of 0 or 1. Indeed, it has been seen
that in advanced-stage disease, chemotherapy offers modest improvements in median survival, with overall survival
being poor [9,10].
Of the novel nonplatinum agents of the last decade,
gemcitabine is widely used for the treatment of NSCLC
[11,12]. Randomized clinical trials support the use of gemcitabine in combination with other cytotoxic agents due
to its unique mechanism of action, lack of overlapping
toxicity, and favorable toxicity prole. Although there
are no standard platinum-based regimens for advanced
NSCLC, gemcitabine in combination with cisplatin has
shown good activity and an acceptable toxicity prole for
the treatment of patients with stage IIIB or IV NSCLC
[13,14].
One factor to consider in interpreting our results is that
prices for Portugal were estimated for 2003, while the
results already published for other European countries used
prices for 2000. This may underestimate the costs in the
other European countries in comparison with Portugal. It
should also be noted that treatment patterns followed under
the Schiller and Comella trials might have evolved in the
time period between the conduct of these clinical trials and
their publications (changes in cycle length, doses, etc.).
Another limitation of this study is that no indirect costs
were included. In non-urban areas, where access to treatment centers is difcult, one should consider the number
of visits a patient must make to complete one cycle. Some
NSCLC treatment regimens require more than one administration per cycle. In addition to costs associated with the
transport of patients, there are the indirect costs associated
with work absence and loss of productivity of the patients
and the relatives who typically accompany these patients to
treatment.
It should also be noted that since this is a costminimization analysis, the economic evidence here presented can be considered less powerful than the evidence
that would be retained from a cost-effectiveness or costutility analysis.
In conclusion, our study represents an important contribution to Portugal regarding the economic value of current chemotherapies in the treatment of NSCLC, and suggests that Gem/Cis can be utilized as a cost-saving treatment over other chemotherapy options in the treatment
of patients with this disease in Portugal. Future studies of quality of life and cost may enable patients and
their clinicians to make better treatment choices for these
patients.

371

Acknowledgement
The study and this publication were funded by Lilly Portugal
Produtos Farmac
euticos, Portugal.

References
[1] World Health Organization. European health for all database
(HFA-DB); 2001.
[2] Comella P, Frasci G, Panza N, Manzione L, De Cataldis G, Ciof
R, et al. Randomized trial comparing cisplatin, gemcitabine,
and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer:
interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group. J Clin Oncol 2000;18:14517.
[3] Schiller JH, Harrington D, Belani CP, Langer C, Sandler
A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med
2002;346:928.
[4] Schiller J, Tilden D, Aristides M, Lees M, Kielhorn A, Maniadakis N, et al. Retrospective cost analysis of gemcitabine in
combination with cisplatin in non-small cell lung cancer compared to other combination therapies in Europe. Lung Cancer
2004;43:10112.
[5] Diagnosis Related Groups (DRG) published at Di
ario da
Rep
ublica; February 2003.
[6] Cat@logo de Aprovisionamento P
ublico da Sa
ude; 2003. Available from: http://www.catalogo.min-saude.pt/CAPS/publico/
default.asp.
[7] National Therapeutic Index, Portugal; 2003.
[8] Chu E, De Vita V. Cancer Chemotherapy Drug Manual. Sudbury,
Massachussetts: Jones and Bartlett publishers; 2005.
[9] Souquet PJ, Chauvin F, Boissel JP, Cellerino R, Cormier Y, Ganz
PA, et al. Polychemotherapy in advanced non small cell lung
cancer: a meta-analysis. Lancet 1993;342:1921.
[10] Non-Small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using
updated data on individual patients from 52 randomised clinical trials. BMJ 1995;311:899909.
[11] Manegold C. Gemcitabine (Gemzar) in non-small cell lung cancer. Expert Rev Anticancer Ther 2004;4:34560.
[12] Manegold C, Zatloukal P, Krejcy K, Blatter J. Gemcitabine
in non-small cell lung cancer (NSCLC). Invest New Drugs
2000;18:2942.
[13] Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier
Y, Gatzemeier U, et al. Phase III trial of gemcitabine
plus cisplatin versus cisplatin alone in patients with locally
advanced or metastatic non-small-cell lung cancer. J Clin Oncol
2000;18:12230.
[14] Le Chevalier T, Scagliotti G, Natale R, Danson S, Rosell R, Stahel
R, et al. Efcacy of gemcitabine plus platinum chemotherapy compared with other platinum containing regimens in
advanced non-small cell lung cancer: a meta-analysis of survival outcomes. Lung Cancer 2005;47:6980.