Survival of Stage 3,4 Non-Small-Cell Lung Cancer

Transcription

Survival of Stage IIIb and IV Non-Small Cell
Lung Cancer Patients on Best Supportive Care in
Manitoba, Canada
Erich Kliewer
Alain Demers
Sri Navaratnam
Coreen Hildebrand
Grace Musto
Report for AstraZeneca Canada Inc.
October, 2002
TABLE OF CONTENTS
1. BACKGROUND.............................................................................................................. 1
2. METHODS....................................................................................................................... 2
2.1 Population.................................................................................................................... 2
2.2 Data ............................................................................................................................. 2
2.3 Analysis ....................................................................................................................... 3
3. RESULTS ......................................................................................................................... 4
3.1 Lung cancer in Manitoba............................................................................................. 4
3.2 Age and stage of BSC NSCLC cases .......................................................................... 5
3.3 Representativeness of BSC NSCLC cases .................................................................. 9
3.4 Chemotherapy ........................................................................................................... 10
3.5 Metastases ................................................................................................................. 17
3.6 Performance status .................................................................................................... 18
3.7 Survival ..................................................................................................................... 19
4. DISCUSSION................................................................................................................. 22
5. REFERENCES .............................................................................................................. 25
i
TABLES
Table 1. Type of incident trachea, bronchus and lung cancer cases by year of
diagnosis and sex, Manitoba 1997-2000..................................................................................4
Table 2. Morphology of the trachea, bronchus and lung cancer cases by year of
diagnosis and sex, Manitoba 1997-2000..................................................................................5
Table 3. Age at diagnosis of NSCLC cases by year of diagnosis and sex, Manitoba
1997-2000 ................................................................................................................................6
Table 4. Age at diagnosis of BSC NSCLC cases by year of diagnosis and sex,
Manitoba January 1997 - June 2000 ........................................................................................7
Table 5. Stage distribution of BSC NSCLC cases by year of diagnosis and sex,
Manitoba 1997 - June, 2000 ....................................................................................................8
Table 6. Stage distribution of BSC NSCLC cases by age at diagnosis and sex,
Manitoba 1997 - June 2000 .....................................................................................................8
Table 7. Characteristics of all Manitoba NSCLC cases and 150 BSC NSCLC cases ....................9
Table 8. Length (days) of chemotherapy lines and time between lines........................................10
Table 9. Patients who had changes in their chemotherapy drugs by number of changes
and line...................................................................................................................................10
Table 10. Reason for changing the chemotherapy drug by line ...................................................11
Table 11. Reason for stopping chemotherapy by line...................................................................11
Table 12. Type of chemotherapy by year of diagnosis and line (intent to treat) ..........................12
Table 13. Type of chemotherapy administered to the BSC NSCLC cases by stage at
diagnosis and line (intent to treat)..........................................................................................13
Table 14. Distribution of chemotherapy by dose (intent to treat) and line for BSC
NSCLC cases .........................................................................................................................14
Table 15. Distribution of chemotherapy by dose (intent to treat) and line for stage IIIb
BSC NSCLC cases.................................................................................................................15
Table 16. Distribution of chemotherapy by dose (intent to treat) and line for stage IV
BSC NSCLC cases.................................................................................................................16
Table 17. Sequence of chemotherapy treatments for the BSC NSCLC cases who
received line 2 and line 3 treatments......................................................................................17
Table 18. Number of metastases in the BSC NSCLC cases by site .............................................17
Table 19. Performance status of BSC NSCLC cases....................................................................18
Table 20. Number of person-weeks accrued by BSC NSCLC cases from diagnosis
date, first and last chemotherapy date and BSC date.............................................................19
Table 21. Survival of BSC NSCLC patients from diagnosis date, by stage at diagnosis
and line...................................................................................................................................21
Table 22. Survival of BSC NSCLC patients from first date of chemotherapy, by stage
at diagnosis and line...............................................................................................................21
Table 23. Survival of BSC NSCLC patients from last day of chemotherapy, by stage
at diagnosis and line...............................................................................................................21
Table 24. Survival of BSC NSCLC patients from BSC date, by stage at diagnosis and
line .........................................................................................................................................22
ii
FIGURES
Figure 1. Age (at diagnosis) distribution of BSC NSCLC cases by sex......................................... 7
Figure 2. Survival distribution of BSC NSCLC cases by diagnosis date, dates of first and
last chemotherapy and BSC date. ......................................................................................... 20
APPENDICES
Appendix 1. Classification of lung cancer according to morphology ..........................................29
Appendix 2. Morphology of the trachea, bronchus and lung cancer cases diagnosed in
Manitoba, 1997-2000.............................................................................................................30
Appendix 3.1 Distribution of chemotherapy according to schedule (line and cycle) for
BSC NSCLC cases.................................................................................................................31
stage IIIb BSC NSCLC cases ................................................................................................32
stage IV BSC NSCLC cases ..................................................................................................33
Appendix 3.4 First line chemotherapy for the 17 stage IIIb and IV BSC NSCLC cases who
received second line chemotherapy .......................................................................................34
Appendix 3.5 First and second line chemotherapy for the stage IV BSC NSCLC cases
who received second line chemotherapy ...............................................................................35
iii
iv
1. BACKGROUND
Lung cancer is the second most common form of cancer in Canadian men and women and
the leading cause of cancer death.1 It has been estimated that 21,200 Canadians were diagnosed
with lung cancer cases in 2001.1 The two predominant types encountered are non-small cell lung
cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is a heterogeneous aggregate of
distinct histological types of lung cancer, including squamous cell carcinoma, adenocarcinoma,
large cell carcinoma and some rare subtypes such as adenosquamous cell carcinoma,
mucoepidermoid carcinoma and adenoid cystic carcinoma. NSCLC tends to be extremely lethal
and respond poorly to chemotherapy. SCLC includes pure small and large cell cancer, mixed
small cell carcinoma and combined (small cell and squamous) carcinoma.2 These cancers are
more responsive to chemotherapy than NSCLC.3,4
Approximately 75 to 80% of lung cancers are NSCLC
50% to 65% are of stage IIIb and IV,
7-10
2,5-7
and of these, approximately
depending on the study population. Most people
diagnosed with lung cancer die of the disease. It was reported that only 14% of Canadian men
and 17% of Canadian women diagnosed with lung cancer in 1992 survived five years or more.11
Survival, however, varies considerably according to the stage at which tumors are diagnosed.
While 38% to 61% of stage I lung cancer patients are expected to survive five years, only 1% of
stage IV cancer patients are expected to live that long.3, 5
As noted by Dranitsaris et al.12, “The role of chemotherapy in advanced NSCLC became
more clearly defined with the publication of four meta-analyses that showed a prolongation of
survival after chemotherapy compared with best supportive care”.13-16 Clinical guidelines from
several countries have recommended chemotherapy for stage IIIB and IV NSCLC patients who
have a relatively good performance status (ECOG 0,1 and select 2).17-21 The meta-analysis by the
Non-Small Cell Lung Cancer Collaborative Group indicated that late stage NSCLC patients
receiving BSC plus chemotherapy had a 10% increase in one-year survival or an increased
median survival of 1.5 months relative to patients on BSC only.16 According to Giaccone, the
use of chemotherapy for patients with stage III NSCLC and malignant pleural effusion, or with
stage IV disease, can result in a 1-year survival of about 35-40% and a median survival of
approximately 9 months.22 However, once a patient has progressed on or relapsed after
chemotherapy, s/he is treated with best supportive care (BSC) which usually consists of
symptomatic therapy and palliative radiation in some cases.
1
This report focuses on patients diagnosed with late stage (stages IIIb and IV) NSCLC in
Manitoba during the period 1997 to June, 2000 and who were receiving BSC. The objective of
the report is to define the characteristics of the BSC patients and their tumors, their
chemotherapy treatment prior to being placed on BSC, and their survival. A second report will
examine the treatment received during BSC and will estimate the costs associated with treatment
patients receive during BSC.
2. METHODS
2.1 Population
Manitoba residents diagnosed with trachea, bronchus and lung cancer (ICD-9 162)
between 1997 and June, 2000 were identified from the Manitoba Cancer Registry. It was
possible to identify which of these cases were NSCLC from the morphology information
recorded in the registry. The morphology codes used to define NSCLC cases are shown in
Appendix 1. The charts of patients with NSCLC were reviewed in order to determine those who
had been diagnosed at stage IIIb and had pleural effusions or supraclavicular involvement, or
those who had been diagnosed at stage IV.
Of these patients, those who had been on
chemotherapy and who survived 28 or more days after their last chemotherapy were considered
to be in the BSC phase of their disease. Four weeks was chosen in order to ensure the patient was
no longer on chemotherapy.
2.2 Data
The information for this report was derived from a variety of sources including the
Manitoba Cancer Registry (MCR), the OpTx system and chart review. The MCR is legally
mandated to collect information on people diagnosed with cancer in Manitoba, as well as
information on their tumor and treatment. Although the MCR does include some treatment
information, it is incomplete. Vital status is recorded in the registry based on death records
provided by the provincial Department of Vital Statistics. The MCR has been population-based
since 1956.
OpTx is a software package that has been specifically developed for cancer treatment
centers for the purposes of tracking patients' appointments, treatment and other health care use.
2
Patient demographic and diagnostic information is also contained in OpTx. Not all Manitoba
cancer cases are included in OpTx as it is primarily used for patients seen at CancerCare
Manitoba or at one of the regional sites associated with the Manitoba Community Cancer
Network.
In order to identify cases of NSCLC that met our BSC definition we first obtained a listing
of 300 records from the Manitoba Cancer Registry that included only the NSCLC cases
diagnosed in Manitoba between January 1, 1997 and December 31, 1999 and who received
chemotherapy. The electronic registry abstract, progress notes, and progression screens of these
300 cases were reviewed to determine eligibility according to the study proposal (stage IIIb with
either pleural effusion or supraclavicular lymph node metastasis) or stage IV (distant metastatic
disease). Ninety cases did not meet these criteria. The OpTx and paper records of the resulting
210 cases were reviewed to assess BSC and to confirm staging. Cases where the staging or
progression could not be confirmed by electronic record review were also included in the paper
chart review. Approximately 120 cases were eligible for the study. Since we required a minimum
of 150 cases, this process was repeated for lung cases diagnosed between January 1, 2000 and
June 20, 2000 (approximately 100 electronic records, 40 paper records).
A detailed chart review was done in four Winnipeg hospitals for 50 cases (diagnosis years
1997 through 2000) for whom insufficient data could be obtained from the CancerCare Manitoba
records in order to determine BSC status.
The procedure, ancillary drug, hospital/clinic admission, radiotherapy treatment, and
chemotherapy dates and dosage data were abstracted from the paper and electronic records and
recorded on an access database.
2.3 Analysis
Survival time was measured from the initial cancer diagnosis date, from the dates of first
and last chemotherapy, as well as from the time at which a patient entered into the BSC phase
(i.e. had been diagnosed at stage IIIb with pleural effusions or supraclavicular involvement, or
had been diagnosed at stage IV and had been on chemotherapy and had survived at least 28 days
from date of last chemotherapy). The end date was either the death date, emigration date (derived
form the Manitoba Health Population Registry) or the study end date of March 31, 2002.
Survival was calculated by the Kaplan-Meier method using SAS v8.223.
3
3. RESULTS
3.1 Lung cancer in Manitoba
In the four-year period 1997-2000 there were 3,091 new cases of trachea, bronchus and
lung cancer diagnosed in Manitoba. Of these, 35 were second primaries. The cases consisted
predominantly of cancers of the upper lobe (46.6%), followed by the lower lobe (23.4%). These
percentages were similar for males and females (Table 1). The majority (79.7%) of these cancers
were NSCLC (Table 2). The proportion of cancers that were NSCLC was similar in males
(80.3%) and females (78.8%). The distribution of first primary cases by detailed morphology is
provided in Appendix 2.
Table 1. Type of incident trachea, bronchus and lung cancer cases by year of diagnosis and sex,
Manitoba 1997-2000
1997
ICD-9
1620
1622
1623
1624
1625
1628
1629
Site
Trachea
Main bronchus
Upper lobe
Middle lobe
Lower lobe
Other parts
Unspecified
Total
1620
1622
1623
1624
1625
1628
1629
Trachea
Main bronchus
Upper lobe
Middle lobe
Lower lobe
Other parts
Unspecified
Total
1620
1622
1623
1624
1625
1628
1629
Trachea
Main bronchus
Upper lobe
Middle lobe
Lower lobe
Other parts
Unspecified
Total
N
1
24
194
13
102
24
71
429
2
19
154
20
72
16
48
331
3
43
348
33
174
40
119
760
1998
%
0.2
5.6
45.2
3.0
23.8
5.6
16.6
100.0
0.6
5.7
46.5
6.0
21.8
4.8
14.5
100.0
0.4
5.7
45.8
4.3
22.9
5.3
15.7
100.0
N
-42
204
13
110
31
60
460
1
17
159
17
82
16
40
332
1
59
363
30
192
47
100
792
1999
%
N
Total1
2000
%
N
%
N
%
-9.1
44.3
2.8
23.9
6.7
13.0
100.0
Males
2
0.4
49
11.0
201
45.1
16
3.6
84
18.8
15
3.4
79
17.7
446 100.0
-27
212
14
114
9
70
446
-6.1
47.5
3.1
25.6
2.0
15.7
100.0
3
142
811
56
410
79
280
1781
0.2
8.0
45.5
3.1
23.0
4.4
15.7
100.0
0.3
5.1
47.9
5.1
24.7
4.8
12.0
100.0
Females
1
0.3
23
7.2
152
47.6
17
5.3
79
24.8
10
3.1
37
11.6
319 100.0
1
17
163
14
80
8
45
328
0.3
5.2
49.7
4.3
24.4
2.4
13.7
100.0
5
76
628
68
313
50
170
1310
0.4
5.8
47.9
5.2
23.9
3.8
13.0
100.0
0.1
7.4
45.8
3.8
24.2
5.9
12.6
100.0
Total
3
0.4
72
9.4
353
46.1
33
4.3
163
21.3
25
3.3
116
15.2
765 100.0
1
44
375
28
194
17
115
774
0.1
5.7
48.4
3.6
25.1
2.2
14.9
100.0
8
218
1439
124
723
129
450
3091
0.3
7.1
46.6
4.0
23.4
4.2
14.6
100.0
1. 3056 individuals were diagnosed with a total of 3091 primary cancers
4
Table 2. Morphology of the trachea, bronchus and lung cancer cases by year of diagnosis and
sex, Manitoba 1997-2000
1997
Type1
N
NSCLC
SCLC
Other
Total
NSCLC
SCLC
Other
Total
NSCLC
SCLC
Other
Total
353
40
36
429
1998
%
82.3
9.3
8.4
100.0
N
373
51
36
460
1999
%
N
Total2
2000
%
N
%
N
%
81.1
11.1
7.8
100.0
Males
342
76.7
58
13.0
46
10.3
446
100.0
363
46
37
446
81.4
10.3
8.3
100.0
1431
195
155
1781
80.3
10.9
8.7
100.0
Females
253
79.6
41
12.9
24
7.5
258
43
27
78.7
13.1
8.2
1032
171
106
78.8
13.1
8.1
253
46
32
76.4
13.9
9.7
268
41
23
80.7
12.3
6.9
331
100.0
332
100.0
318
100.0
328
100.0
1309
100.0
80.9
11.6
7.4
100.0
Total
595
77.9
99
13.0
70
9.2
764
100.0
621
89
64
774
80.2
11.5
8.3
100.0
2463
366
261
3090
79.7
11.8
8.4
100.0
606
86
68
760
79.7
11.3
8.9
100.0
641
92
59
792
1. There was one case who had an unknown tumor type
The majority of Manitoba NSCLC cases were males (58.1%). The age distribution of the
NSCLC cases are shown in Table 3. NSCLC is concentrated in individuals over the age of 54.
Compared to females (64.4%), a somewhat greater proportion of men (69.7%) were 65 years of
age and over.
3.2 Age and stage of BSC NSCLC cases
For the period 1997-June, 2000 we identified 150 NSCLC cases that met the criteria for the
BSC case definition. The age (at diagnosis) distribution of these cases is shown in Table 4 by
year of diagnosis and sex. Fifty-six percent of the BSC cases were males. The male cases tended
to be older than the female cases. The majority of male BSC cases were 65-74 years of age at the
time of diagnosis, whereas the majority of female cases were 55-64 years old (Figure 1).
Overall, a slightly greater percentage of males (79.8%) than females (75.8%) were
diagnosed at stage IV NSCLC (Table 5). However, the percentage of females diagnosed with
stage IV disease has been increasing since 1997, although this is based on a relatively small
number of cases.
5
Table 3. Age at diagnosis of NSCLC cases by year of diagnosis and sex, Manitoba 1997-2000
1997
1998
%
N
1999
%
N
Total2
2000
Age
N
%
N
%
N
%
<35
35-44
45-54
55-64
65-74
≥75
Total
1
3
21
75
126
127
353
0.3
0.8
5.9
21.2
35.7
36.0
100.0
2
4
23
85
132
127
373
0.5
1.1
6.2
22.8
35.4
34.0
100.0
-1
25
74
122
120
342
-0.3
7.3
21.6
35.7
35.1
100.0
1
4
27
87
111
133
363
0.3
1.1
7.4
24.0
30.6
36.6
100.0
4
12
96
321
491
507
1431
0.3
0.8
6.7
22.4
34.3
35.4
100.0
<35
35-44
45-54
55-64
65-74
≥75
Total
-3
36
53
87
74
253
-1.2
14.2
20.9
34.4
29.2
100.0
-2
20
66
83
97
268
-0.7
7.5
24.6
31.0
36.2
100.0
Females
1
0.4
7
2.8
27
10.7
60
23.7
93
36.8
65
25.7
253
100.0
1
7
26
59
74
91
258
0.4
2.7
10.1
22.9
28.7
35.3
100.0
2
19
109
238
337
327
1032
0.2
1.8
10.6
23.1
32.7
31.7
100.0
2
11
53
146
185
224
621
0.3
1.8
8.5
23.5
29.8
36.1
100.0
6
31
205
559
828
834
2463
0.2
1.3
8.3
22.7
33.6
33.9
100.0
Males
Total
<35
35-44
45-54
55-64
65-74
75-00
Total
1
6
57
128
213
201
606
0.2
1.0
9.4
21.1
35.1
33.1
100.0
2
6
43
151
215
224
641
0.3
0.9
6.7
20.0
33.5
34.9
100.0
1
8
52
134
215
185
595
0.2
1.3
8.7
22.5
36.1
31.1
100.0
1. There was one case who had an unknown tumor type
There was a greater proportion of people under the age of 55 among those diagnosed at
Stage IV (27.4%) than among those diagnosed at Stage IIIb (12.1%) (Table 6). This was evident
for both males and females. As noted above, women tended to be diagnosed at an earlier age
than men, and this pattern occurred among both stage IIIb and stage IV cases.
6
Table 4. Age at diagnosis of BSC NSCLC cases by year of diagnosis and sex, Manitoba January
1997 - June 2000
1997
Age
1998
N
%
N
1999
%
2000
N
%
N
Total
%
N
%
Males
< 35
35-44
45-54
55-64
65-74
≥75
--4
4
8
1
--23.5
23.5
47.1
5.9
-2
4
7
7
2
-9.1
18.2
31.8
31.8
9.1
--3
11
10
1
--12.0
44.0
40.0
4.0
-1
1
7
6
5
-5.0
5.0
35.0
30.0
25.0
-3
12
29
31
9
-3.6
14.3
34.5
36.9
10.7
Total
17
100.0
22
100.0
25
100.0
20
100.0
84
100.0
Females
1
2.9
2
5.7
7
20.0
12
34.3
10
28.6
3
8.6
--4
2
4
--
--40.0
20.0
40.0
--
1
2
18
22
19
4
1.5
3.0
27.3
33.3
28.8
6.1
10
100.0
66
100.0
< 35
35-44
45-54
55-64
65-74
≥75
--3
3
3
--
--33.3
33.3
33.3
--
--4
5
2
1
--33.3
41.7
16.7
8.3
Total
9
100.0
12
100.0
35
100.0
Total
< 35
35-44
45-54
55-64
65-74
≥75
--7
7
11
1
--26.9
26.9
42.3
3.8
-2
8
12
9
3
-5.9
23.5
35.3
26.5
8.8
1
2
10
23
20
4
1.7
3.3
16.7
38.3
33.3
6.7
-1
5
9
10
5
-3.3
16.7
30.0
33.3
16.7
1
5
30
51
50
13
0.7
3.3
20.0
34.0
33.3
8.7
Total
26
100.0
34
100.0
60
100.0
30
100.0
150
100.0
Figure 1. Age (at diagnosis) distribution of BSC NSCLC cases by sex
40
Female
35
Male
30
Percent
25
20
15
10
5
0
< 35
35-44
45-54
55-64
Age
7
65-74
> 74
Table 5. Stage distribution of BSC NSCLC cases by year of diagnosis and sex, Manitoba 1997 June, 2000
1997
Stage
N
1998
%
N
1999
%
2000
N
Total
%
N
%
N
%
Males
IIIb
IV
5
12
29.4
70.6
-22
-100.0
8
17
32.0
68.0
4
16
20.0
80.0
17
67
20.2
79.8
Total
17
100.0
22
100.0
25
100.0
20
100.0
84
100.0
Females
8
22.9
27
77.1
2
8
20.0
80.0
16
50
24.2
75.8
10
100.0
66
100.0
IIIb
IV
3
6
33.3
66.7
3
9
25.0
75.0
Total
9
100.0
12
100.0
35
100.0
Total
IIIb
IV
8
18
30.8
69.2
3
31
8.8
91.2
16
44
26.7
73.3
6
24
20.0
80.0
33
117
22.0
78.0
Total
26
100.0
34
100.0
60
100.0
30
100.0
150
100.0
Table 6. Stage distribution of BSC NSCLC cases by age at diagnosis and sex, Manitoba 1997 June 2000
IIIb
Age
N
IV
%
N
Total
%
N
%
Males
< 35
35-44
45-54
55-64
65-74
≥75
--1
6
8
2
--5.9
35.3
47.1
11.8
-3
11
23
23
7
-4.5
16.4
34.3
34.3
10.4
-3
12
29
31
9
-3.6
14.3
34.5
36.9
10.7
Total
17
100.0
67
100.0
84
100.0
< 35
35-44
45-54
55-64
65-74
≥75
-1
2
9
4
--
-6.3
12.5
56.3
25.0
--
1
1
16
13
15
4
2.0
2.0
32.0
26.0
30.0
8.0
1
2
18
22
19
4
1.5
3.0
27.3
33.3
28.8
6.1
Total
16
100.0
50
100.0
66
100.0
Females
Total
< 35
35-44
45-54
55-64
65-74
≥75
-1
3
15
12
2
-3.0
9.1
45.5
36.4
6.1
1
4
27
36
38
11
0.9
3.4
23.1
30.8
32.5
9.4
1
5
30
51
50
13
0.7
3.3
20.0
34.0
33.3
8.7
Total
33
100.0
117
100.0
150
100.0
8
3.3 Representativeness of BSC NSCLC cases
From the data available for this report, it is not possible to determine how representative
the sample of 150 BSC NSCLC (as defined for this report) cases are of all Manitoba BSC
NSCLC cases. In order to do so, we would require information on other Manitoba BSC cases. As
noted, meta-analyses have shown the benefit of receiving chemotherapy in the BSC phase and
clinical guidelines have called for chemotherapy for certain late stage NSCLC cases. As the case
definition used for this report excludes any cases who had chemotherapy while on BSC and
those who survived less than 28 days after last receiving chemotherapy, the sample may well not
be representative of all Manitoba BSC cases.
Table 7 provides a limited comparison of the characteristics of the 150 BSC cases relative
to all NSCLC cases in Manitoba. A similar proportion of NSCLC cases was diagnosed in each of
the years in the period 1997-2000. In contrast, the majority of BSC were diagnosed in 1999.
Fewer cases were diagnosed in 2000, as in deriving our sample we only examined cases up to
June, 2000. The sex distribution of the two groups was similar, with males predominating in
both. The BSC cases were substantially younger than all NSCLC cases, with there being
approximately 20-30% fewer people over the age of 64 in the BSC sample than in the NSCLC
cases. In both groups, there was a greater proportion of males than females who were aged 65
years and over. Since it was part of the case definition, all BSC cases had had chemotherapy, but
only 16.8% of NSCLC cases had had chemotherapy (1997 14.2%, 1998 14.7%, 1999 19.3%,
2000 19.0%). It should be noted that the chemotherapy information for all NSCLC cases was
derived from the Manitoba Cancer Registry, which may not be complete.
Table 7. Characteristics of all Manitoba NSCLC cases and 150 BSC NSCLC cases
NSCLC (%) n=2463
BSC (%) n=150
Diagnosis year
1997
1998
1999
2000
24.6
26.1
24.2
25.2
17.3
22.7
40.0
20.0
Sex
Males
Females
58.1
41.9
56.0
44.0
Over 64 years of age
Males
Females
69.7
64.3
47.6
34.8
Received chemotherapy
16.8
100.0
Characteristic
9
3.4 Chemotherapy
As part of the case definition for BSC, all patients had to have received at least one line of
chemotherapy. Seventeen (11.3%) of the 150 BSC patients received a second line of
chemotherapy, while only one patient had a third line. The mean length of time people spent on
line 1 chemotherapy was 82.3 days (Table 8). The mean length of time on chemotherapy was
slightly shorter for those on their second line (75.2 days). For people receiving a second line of
chemotherapy, it started on average 112.6 days after ending their first line of chemotherapy.
Table 8. Length (days) of chemotherapy lines and time between lines
Time length
N
Line 1
Time between line 1 and 2
Line 2
Time between line 2 and 3
Line 3
Mean
150
17
17
1
1
Median
Minimum
Maximum
78
65
86
17
1
1
5
1
17
1
337
355
179
17
1
82.3
112.6
75.2
17.0
1.0
A total of 20 patients had changes in their chemotherapy drugs during line 1 (Table 9). Of
these, three had two changes and one had three changes. During line 2, three patients (17.6%)
changed their drugs once, while the only patient on line 3 had no changes. It should be noted that
these changes are considered by oncologists to be a continuation of first line chemotherapy and
not a move to second line chemotherapy. The reason for changing the chemotherapy drug was
only recorded in the medical charts for 10 of the 25 occurrences (Table 10). Of these, 60% were
due to the toxicity of the first drug tried. Similarly, toxicity was the principal reason for patients
stopping chemotherapy during line 1 (Table 11). Of the five patients on line 2 chemotherapy for
whom the reason for stopping was recorded, three stopped because of disease progression and
two stopped because of toxicity.
Table 9. Patients who had changes in their chemotherapy drugs by number of changes and line
Number of
changes
Line 1
Line 2
Line 3
N
%
N
%
N
0
1
2
3
130
16
3
1
86.7
10.7
2.0
0.7
14
3
---
82.4
17.6
---
1
----
100.0
----
Total
150
100.0
17
1
100.0
100.0
10
%
Table 10. Reason for changing the chemotherapy drug by line
Reason for
changing
Line 1
Line 2
N
%
N
%
Adverse reaction
Intolerance
Lack of effect
Toxicity
NS1
2
1
1
6
15
8.0
4.0
4.0
24.0
58.3
----3
----100.0
Total
25
100.0
3
100.0
1. NS: not stated
Table 11. Reason for stopping chemotherapy by line
Reason for
stopping
Line 1
Line 2
Line 3
Total
N
%
N
%
N
%
N
%
Adverse reaction
Disease progression
Patient refused
Side effects
Toxicity
NS1
1
6
2
4
11
126
0.7
4.0
1.3
2.7
7.3
84.0
-3
--2
12
-17.6
--11.8
70.6
-----1
-----100.0
1
9
2
4
13
140
0.6
5.7
1.3
2.5
8.2
88.1
Total
150
100.0
17
100.0
1
100.0
159
100.0
1. NS: treatment was completed as scheduled or that the reason for stopping was not stated
Overall, cisplatin (51.3%) and carboplatin (42.0%) based chemotherapy were the most
common forms of first line treatment for the patients prior to their entering the BSC phase of
their disease (Table 12). Carboplatin based chemotherapy only started to be used extensively in
1998. Cisplatin was most commonly administered in combination with vinorelbine or etoposide,
although the use of etoposide decreased markedly since 1997. Carboplatin was most commonly
administered in combination with paclitaxel or vinorelbine. The use of vinorelbine in
conjunction with carboplatin has been steadily increasing.
Of the BSC patients who received a second line of chemotherapy, the most common
treatment was cisplatin based (35.3%). Only one patient had a third line of chemotherapy, and
that was docetaxel. The detailed distribution of chemotherapy according to line, cycle and stage
are shown in Appendix 3.
11
Table 12. Type of chemotherapy by year of diagnosis and line (intent to treat1)
1997
Drug(s)
1
N
1998
%
N
1999
%
2000
N
Total
%
N
%
N
%
Line 1
Cisplatin
CIS + VIN
CIS + ETO
CIS + GEM
CIS + PAC
23
10
13
---
88.5
38.5
50.0
---
11
5
5
-1
32.4
14.7
14.7
-2.9
30
21
8
1
--
50.0
35.0
13.3
1.7
--
13
12
1
---
43.3
40.0
3.3
---
77
48
27
1
1
51.3
32.0
18.0
0.7
0.7
Carboplatin
CAR + PAC
CAR + VIN
CAR + ETO
2
-2
--
7.7
-7.7
--
22
9
6
7
64.7
26.5
17.6
20.6
26
15
11
--
43.3
25.0
18.3
--
13
5
8
--
43.3
16.7
26.7
--
63
29
27
7
42.0
19.3
18.0
4.7
Vinorelbine
Other
-1
-3.8
1
--
2.9
--
3
1
5.0
1.7
3
1
10.0
3.3
7
3
4.7
2.0
26
100.0
34
100.0
60
100.0
30
100.0
150
100.0
Line 2
4
36.4
1
9.1
3
27.3
---
1
--1
20.0
--20.0
6
1
3
2
35.3
5.9
17.6
11.8
Total
Cisplatin
CIS + VIN
CIS + ETO
CIS + GEM
-----
-----
1
--1
100.0
--100.0
Carboplatin
CAR + PAC
CAR + VIN
CAR + ETO + ADR + BLE
-----
-----
-----
-----
3
-2
1
27.3
-18.2
9.1
1
1
---
20.0
20.0
---
4
1
2
1
23.5
5.9
11.8
5.9
Vinorelbine
Docetaxel
Total
----
---
--1
--100.0
2
2
11
18.2
18.2
100.0
1
2
5
20.0
40.0
100.0
3
4
17
17.6
23.5
100.0
--
--
1
100.0
Line 3
Docetaxel
--
--
1
100.0
--
--
1. Dose given on first cycle
2. ADR: adriamycin, BLE: bleomycin, CAR: carboplatin, CIS: cisplatin, ETO: etoposide, GEM: gemcitabine, PAC: paclitaxel,
VIN: vinorelbine
There were some variations in the chemotherapy treatment of patients depending on the
stage of their disease at the time of diagnosis (Table 13). For their first line treatment, stage IIIb
patients primarily received cisplatin (63.6%) based chemotherapy. For stage IV patients, first
line chemotherapy was equally divided between cisplatin (42.9%) and carboplatin (42.9%).
Unlike stage IIIb patients, some stage IV patients received vinorelbine or other types of first line
chemotherapy. Although second and third line chemotherapy have been included in Table 13,
there are too few patients to make any reliable observations.
12
Table 13. Type of chemotherapy administered to the BSC NSCLC cases by stage at diagnosis
and line (intent to treat1)
IIIb
Drug(s)
1
N
IV
%
N
Total
%
N
%
Line 1
Cisplatin
CIS + VIN
CIS + ETO
CIS + GEM
CIS + PAC
21
12
9
---
63.6
36.4
27.3
---
56
36
18
1
1
47.9
30.8
15.4
0.9
0.9
77
48
27
1
1
51.3
32.0
18.0
0.7
0.7
Carboplatin
CAR + PAC
CAR + VIN
CAR + ETO
12
6
6
--
36.4
18.2
18.2
--
51
23
21
7
43.6
19.7
17.9
6.0
63
29
27
7
42.0
19.3
18.0
4.7
Vinorelbine
Other
---
---
7
3
6.0
2.6
7
3
4.7
2.0
33
100.0
117
100.0
150
100.0
Cisplatin
CIS + VIN
CIS + ETO
CIS + GEM
3
1
1
1
42.9
----
3
-2
1
30.0
-20.0
10.0
6
1
3
2
35.3
5.9
17.6
11.8
Carboplatin
CAR + PAC
CAR + VIN
3
-2
1
42.9
----
1
1
---
10.0
10.0
---
4
1
2
1
23.5
5.9
11.8
5.9
Vinorelbine
Docetaxel
Total
1
-7
14.3
-100.0
2
4
10
20.0
40.0
100.0
3
4
17
17.6
23.5
100.0
100.0
--
--
1
100.0
Total
Line 2
Line 3
Docetaxel
1
1. Dose given on first cycle
2. ADR: adriamycin, BLE: bleomycin, CAR: carboplatin, CIS: cisplatin, ETO: etoposide, GEM: gemcitabine, PAC: paclitaxel,
VIN: vinorelbine
There was often a wide range in the dose of a particular drug or combination of drugs that
was administered. Table 14 provides the dose distribution for each drug or combination of drugs
for each line. Overall and for Stage IV patients (Table 16), the single most frequently
administered chemotherapy on the first cycle of the first line was 6 mg/ml.min of carboplatin and
25 mg/m2 of vinorelbine, while 6 mg/ml.min of carboplatin and 200 mg/m2 of paclitaxel was the
second most common form of chemotherapy. For stage IIIb patients, 6 mg/ml.min of carboplatin
and 25 mg/m2 of vinorelbine or 75 mg/m2 of cisplatin and 25 mg/m2 of vinorelbine were equally
common treatments (Table 15).
13
Table 14. Distribution of chemotherapy by dose (intent to treat1) and line for BSC NSCLC cases
Line 1
Drug(s)
2
Line 2
Line 3
Dose
N
%
N
%
N
CIS + VIN
75 mg/m2 + 20 mg/m2
75 mg/m2 + 25 mg/m2
75 mg/m2 + 30 mg/m2
100 mg/m2 + 25 mg/m2
100 mg/m2 + 40 mg/m2
120 mg/m2 + 30 mg/m2
NS
3
16
4
14
1
1
9
2.0
10.7
2.7
9.3
0.7
0.7
6.0
-1
------
-5.9
------
--------
--------
CIS + ETO
25 mg/m2 + 75 mg/m2
25 mg/m2 + 100 mg/m2
30 mg/m2 + 100 mg/m2
50 mg/m2 + 50 mg/m2
75 mg/m2 + 100 mg/m2
100 mg/m2 + 100 mg/m2
NS
1
9
1
3
2
1
10
0.7
6.0
0.7
2.0
1.3
0.7
6.7
------3
------17.6
--------
--------
CIS + GEM
75 mg/m2 + 1000 mg/m2
50 mg/m2 + 1250 mg/m2
75 mg/m2 + 1250 mg/m2
1
---
0.7
---
-1
1
-5.9
5.9
----
----
CIS + PAC
NS
1
0.7
--
--
--
--
CAR + PAC
3 mg/ml.min + 60 mg/m2
NS
1
-1
4
20
3
0.7
-0.7
2.7
13.3
2.0
-1
-----
-5.9
-----
-------
-------
CAR + VIN
6 mg/ml.min +25 mg/m2
NS
26
1
17.3
0.7
2
--
11.8
--
---
---
CAR + ETO
6 mg/ml.min+ 75 mg/m2
NS
6
1
4.0
0.7
---
---
---
---
CAR + ETO + ADR + BLE NS
--
--
1
5.9
--
--
VIN
25 mg/m2
30 mg/m2
NS
5
1
1
3.3
0.7
0.7
1
-2
5.9
-11.8
DOC
36 mg/m2
75 mg/m2
100 mg/m2
NS
-----
-----
1
1
-2
5.9
5.9
-11.8
-----
-----
-1
--
-100.0
--
NS
3
2.0
--
--
--
--
150
100.0
17
100.0
1
100.0
Other
Total
%
1. Dose given on the first cycle
2. ADR: adriamycin, BLE: bleomycin, CAR: carboplatin, CIS: cisplatin, DOC: docetaxel, ETO: etoposide, GEM: gemcitabine,
PAC: paclitaxel, VIN: vinorelbine, NS: not stated
14
Table 15. Distribution of chemotherapy by dose (intent to treat1) and line for stage IIIb BSC
NSCLC cases
Drug(s)2
Dose
Line 1
Line 2
Line 3
N
%
N
%
N
%
CIS + VIN
75 mg/m2 + 20 mg/m2
75 mg/m2 + 25 mg/m2
100 mg/m2 + 25 mg/m2
120 mg/m2 + 30 mg/m2
NS
1
6
1
1
3
3.0
18.2
3.0
3.0
9.1
-1
----
-14.3
----
------
------
CIS + ETO
25 mg/m2 + 100 mg/m2
50 mg/m2 + 50 mg/m2
75 mg/m2 + 100 mg/m2
NS
5
1
1
2
15.2
3.0
3.0
6.1
---1
---14.3
-----
-----
CIS + GEM
50 mg/m2 + 1250 mg/m2
--
--
1
14.3
--
--
CAR + PAC
1
5
3.0
15.2
---
---
---
---
CAR + VIN
6
18.2
2
28.6
--
--
CAR + ETO + ADR + BLE NS
--
--
1
14.3
--
--
VIN
--
--
1
14.3
--
--
33
100.0
7
100.0
--
--
Total
25 mg/m2
15
Table 16. Distribution of chemotherapy by dose (intent to treat1) and line for stage IV BSC
NSCLC cases
Drug(s)2
Dose
Line 1
N
Line 2
Line 3
%
N
%
N
%
CIS + VIN
75 mg/m2 + 20 mg/m2
75 mg/m2 + 25 mg/m2
75 mg/m2 + 30 mg/m2
100 mg/m2 + 25 mg/m2
100 mg/m2 + 40 mg/m2
NS
2
10
4
13
1
6
1.7
8.5
3.4
11.1
0.9
5.1
-------
-------
-------
-------
CIS + ETO
25 mg/m2 + 75 mg/m2
25 mg/m2 + 100 mg/m2
30 mg/m2 + 100 mg/m2
50 mg/m2 + 50 mg/m2
75 mg/m2 + 100 mg/m2
100 mg/m2 + 100 mg/m2
NS
1
4
1
2
1
1
8
0.9
3.4
0.9
1.7
0.9
0.9
6.8
------2
------20.0
--------
--------
1
0.9
--
-1
-10.0
---
---
1
0.9
--
--
--
--
1
4
15
3
-0.9
3.4
12.8
2.6
-----
10.0
-----
------
------
CIS + GEM
75 mg/m2 + 1000 mg/m2
75 mg/m2 + 1250 mg/m2
CIS + PAC
NS
CAR + PAC
NS
---
1
CAR + VIN
NS
20
1
17.1
0.9
---
---
---
---
CAR + ETO
6 mg/ml.min+ 75 mg/m2
NS
6
1
5.1
0.9
---
---
---
---
VIN
25 mg/m2
30 mg/m2
NS
5
1
1
4.3
0.9
0.9
2
---
20.0
---
----
----
1
1
2
20.0
10.0
20.0
---
100
---
--
--
--
DOC
Other
36 mg/m2
75 mg/m2
NS
----
NS
Total
---3
2.7
117
100.0
-10
100.0
1
1
100.0
Although few of the BSC patients received more than one line of chemotherapy, Table 17
shows the chemotherapy they received in subsequent lines, relative to what they received in the
first line. There was no common pattern.
16
Table 17. Sequence of chemotherapy treatments for the BSC NSCLC cases who received line 2
and line 3 treatments
Chemotherapy
Line 1
Line 2
Line 3
CAR + PAC
CAR + PAC
CAR + PAC
CAR + PAC
CAR + VIN
CIS + ETO
CIS + ETO
CIS + GEM
CIS + VIN
CIS + VIN
CIS + VIN
VIN
CAR + VIN
CIS + ETO
CIS + GEM
DOC
CIS + VIN
CIS + GEM
CAR + VIN
DOC
DOC
DOC
VIN
CAR + PAC
Count
%
1
3
1
1
1
1
1
1
1
2
3
1
5.9
17.6
5.9
5.9
5.9
5.9
5.9
5.9
5.9
11.8
17.6
5.9
Total
17
100.0
1. ADR: adriamycin, BLE: bleomycin, CAR: carboplatin, CIS: cisplatin, DOC: docetaxel, ETO: etoposide, GEM:
gemcitabine, PAC: paclitaxel, VIN: vinorelbine
3.5 Metastases
In order to be classified as a Stage IIIb or IV lung cancer, metastases must have occurred.
Of the 150 BSC patients, 119 (79.3%) had at least two metastases at the time of diagnosis or
since diagnosis, and three had six metastases (Table 18). Of the patients that had at least one
metastases, the majority were to the lymph nodes (24.7%), followed by the chest wall (20.7%)
and bone (16.0%).
Table 18. Number of metastases in the BSC NSCLC cases by site1
1
2
3
4
5
6
Site
N
%
N
%
N
%
N
%
N
%
Lymph nodes –extrathoracic
Lymph nodes –supraclavicular
Lymph nodes –mediastinal
Chest wall
Lung
Bone
Adrenal
CNS
Liver
Cutaneous
Other
21
16
-31
28
24
9
8
6
4
3
14.0
10.7
-20.7
18.7
16.0
6.0
5.3
4.0
2.7
2.0
36
4
1
14
16
22
8
5
9
3
1
30.3
3.4
0.8
11.8
13.4
18.5
6.7
4.2
7.6
2.5
0.8
11
3
-3
5
14
9
13
2
4
6
15.7
4.3
-4.3
7.1
20.0
12.9
18.6
2.9
5.7
8.6
3
----6
3
9
2
3
--
11.5
----23.1
11.5
34.6
7.7
11.5
--
1
--1
1
2
1
2
--2
10.0
--10.0
10.0
20.0
10.0
20.0
--20.0
------1 33.3
------1 33.3
1 33.3
-----
150 100 119
100
70
100
25
100
10
100
3
Total
1. If a person had more than one metastasis at the same site it was only counted once.
17
N
Total
%
N
%
72
23
1
50
50
68
30
38
20
14
12
19.0
6.1
0.3
13.2
13.2
18.0
7.9
10.1
5.3
3.7
3.2
100 377
100
3.6 Performance status
The performance status of patients was measured by oncologists at CancerCare Manitoba
using the Eastern Cooperative Oncology Group (ECOG) Performance Status.24 Unfortunately,
this information was poorly reported by physicians. Although comments were often present in
the charts, it was not possible to derive an ECOG score from the comments alone. At the start of
treatment the ECOG was not recorded for 55.3% of patients (Table 19). The ECOG was not
available for 86% of the patients at the time they entered the BSC phase of their treatment. For
those for whom the ECOG was available, at the start of treatment 53.7% were status 1. This
proportion had declined somewhat at the time of BSC to 42.9%. Although the numbers were too
small to track changes over time for individuals, there was an overall decline in status by the
time the patients reached the BSC phase. At start of treatment 23.9% of patients had an ECOG
status code of 2 or greater, while at the time of BSC the percentage had increased to 42.9%.
Table 19. Performance status of BSC NSCLC cases
Before chemotherapy
ECOG code1
NS
0
1
2
3
4
5
3
Total
At BSC date2
Number
%
Number
%
83
15
36
15
1
---
55.3
10.0
24.0
10.0
0.7
---
129
3
9
5
1
-3
86.0
2.0
6.0
3.3
0.7
-2.0
150
100.0
150
100.0
1. ECOG codes
0: Fully active, able to carry on all pre-disease performance without restriction
1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g.,
light housework, office work
2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up about more than 50% of waking
hours
3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5: Dead
2. For three people, the death and BSC dates were the same
3. NS: not stated
18
3.7 Survival
Of the 150 BSC patients, 140 had died and 2 had moved out of the province as of March
31, 2002. At the end of follow-up, the 150 BSC patients had accrued a total of 7744.4
person-weeks (mean 51.6 weeks) accrued from the date they were diagnosed with cancer and
3906.0 person-weeks (mean 26.1) from the date they went onto BSC (Table 20). Table 20 also
shows the results from the date of first and last chemotherapy.
Table 20. Number of person-weeks accrued by BSC NSCLC cases from diagnosis date, first and
last chemotherapy date and BSC date
From
N
Total
Mean
Median
Minimum
Maximum
From diagnosis date
First day of chemotherapy
Last day of chemotherapy
From BSC date1
150
150
150
150
7744.4
6709.1
4506.0
3906.0
51.6
44.7
30.0
26.0
40.6
31.8
17.8
13.8
8.1
4.3
4.0
0.0
206.7
195.7
184.7
180.7
1. BSC date was defined as 28 days after the last chemotherapy treatment ended
The survival curves based on these four dates are shown in Figure 2. Tables 21-24 provide
survival information from each of the four dates by line and stage at diagnosis. The median
survival time since diagnosis was 40.6 weeks, with 30.7% of the cases surviving one year and
11.7% surviving at least two years (Table 21). Since the BSC date the median survival was 13.8
weeks with 16.8% surviving one year and 5.8% surviving two years (Table 24). The median
survival of people diagnosed with stage IV NSCLC was less than that of those diagnosed with
stage IIIb NSCLC, although the differences were not statistically significant. For example, from
BSC date the median survival of stage IV patients was 12.4 weeks compared to 21.4 weeks for
Stage IIIb patients.
The impact of receiving one or two lines of chemotherapy on survival varied according to
the starting point from which survival was calculated, although it needs to be recognized that
these findings are based on only a small number of patients who received more than one line of
chemotherapy. Median survival from date of diagnosis (Table 21) and from date of first
chemotherapy (Table 22) was significantly longer for patients receiving two lines of
chemotherapy than those receiving only one line. However, from the date of last chemotherapy
(Table 23) or from the date of BSC (Table 24), the patients who received more than one line of
chemotherapy had a slightly shorter median survival than those who received only one line of
19
chemotherapy, although the differences were not significant. A similar pattern was observed
among patients diagnosed at stage IV. Patients diagnosed with stage IIIb NSCLC and who
received two lines of chemotherapy had a shorter, but not significantly shorter, survival than the
IIIb patients who received only one line.
Figure 2. Survival distribution of BSC NSCLC cases by diagnosis date, dates of first and last
chemotherapy and BSC date.
1.00
0.75
Diagnosis Date
First Day of Chemotherapy
Survival
Last Day of Chemotherapy
BSC Date
0.50
0.25
0.00
0
26
52
78
104
Weeks
20
130
156
Table 21. Survival of BSC NSCLC patients from diagnosis date, by stage at diagnosis and line
Median
Stage
Line
Total
1
1+2
1 + 2 +3
IIIb
1
1+2
IV
1
1+2
1 + 2 +3
N
150
133
16
1
33
26
7
117
107
9
1
(weeks)
40.6
38.1
61.6
41.4
53.6
55.4
47.3
38.6
36.3
83.3
41.4
Survived 1 year
Survived 2 years
1
(%)
(%)
35.4 – 45.7
33.7 – 43.4
47.3 – 94.3
-36.7 – 67.0
35.4 – 79.3
36.7 – 94.3
32.1 – 42.7
31.4 – 41.3
47.3 - 107.1
--
30.7
27.8
56.3
-51.5
53.9
42.9
24.8
21.5
66.7
11.7
11.0
18.8
-10.1
13.2
-12.0
10.3
33.3
--
95% CI
--
1. 95% confidence interval
Table 22. Survival of BSC NSCLC patients from first date of chemotherapy, by stage at
diagnosis and line
Median
Stage
Line
Total
1
1+2
1 + 2 +3
IIIb
1
1+2
IV
1
1+2
1 + 2 +3
N
150
133
16
1
33
26
7
117
107
9
1
(weeks)
31.8
30.4
60.6
27.1
43.0
46.6
36.4
29.4
29.0
78.0
27.1
Survived 1 year
Survived 2 years
1
(%)
(%)
28.7 – 37.7
26.7 – 34.1
36.4 – 88.4
-30.4 – 60.9
26.7 – 71.0
29.4 – 88.4
27.0 – 36.1
25.1 – 33.0
45.9 – 96.1
--
26.7
23.3
56.3
-45.5
46.2
42.9
21.4
17.8
66.7
--
8.9
8.6
12.5
-10.2
13.5
-8.5
7.5
22.2
--
95% CI
Table 23. Survival of BSC NSCLC patients from last day of chemotherapy, by stage at
diagnosis and line
Median
Stage
Total
Line
1
1+2
1 + 2 +3
IIIb
1
1+2
IV
1
1+2
1 + 2 +3
N
150
133
16
1
33
26
7
117
107
9
1
(weeks)
17.8
18.0
17.4
6.6
25.4
26.1
14.0
16.4
16.4
19.4
6.6
95% CI
1
14.9 – 20.3
14.9 – 20.4
12.3 – 29.0
-17.3 – 40.9
17.6 – 52.3
10.0 – 35.6
13.7 – 19.1
12.6 – 19.1
14.7 – 29.0
--
21
Survived 1 year
Survived 2 years
(%)
(%)
18.9
19.6
14.3
-30.3
34.6
14.3
15.6
15.9
---
5.8
6.3
--7.6
9.6
-5.5
5.6
---
Table 24. Survival of BSC NSCLC patients from BSC date, by stage at diagnosis and line
Median
Stage
Line
Total
1
1+2
1 + 2 +3
IIIb
1
1+2
IV
1
1+2
1 + 2 +3
N
150
133
16
1
33
26
7
117
107
9
1
(weeks)
13.8
14.0
13.4
2.6
21.4
22.1
10.0
12.4
12.4
15.4
2.6
95% CI
1
10.9 – 16.3
10.9 – 16.4
8.3 – 25.0
-13.3 – 36.9
13.6 – 48.3
6.0 – 31.6
9.7 – 15.1
8.6 – 15.1
10.7 – 25.0
--
Survived 1 year
Survived 2 years
(%)
(%)
16.8
17.3
14.3
-21.2
23.1
14.3
15.6
15.9
---
5.8
6.3
--7.6
9.6
-5.5
5.6
---
4. DISCUSSION
This report has provided some descriptive epidemiological information on all lung cancer
patients diagnosed in Manitoba between 1997 and 2000. Similar descriptive information as well
as survival analyses have been provided for 150 patients diagnosed with stage IV/IIIB
(supraclavicular node involvement or pleural effusion) NSCLC who received either first or
second line chemotherapy and survived more than 28 days after completion of chemotherapy.
The majority of lung cancer patients in Manitoba (79.7%) were NSCLC. Similar
proportions have been reported in other regions.2,5-7 The NSCLC cases consisted of more males
(58.1%) than females. Women with NSCLC tended to be diagnosed at a younger age than men.
Similar findings have been reported by Radzikowska et al.25
The sample of BSC NSCLC patients may not be representative of all Manitoba BSC
patients. All the patients in the BSC sample received chemotherapy prior to BSC, but it is not
known what percentage of all Manitoba BSC patients had similar treatment. Also, amongst all
BSC patients chemotherapy may have been provided to some after they were put on BSC in
order to improve quality of life.16,26,27 None of the BSC sample had chemotherapy after the BSC
date. The BSC sample also had to have survived at least 28 days after their last chemotherapy
treatment.
There were 150 patients who were initially diagnosed with NSCLC in the period of 1997 to
June 2000 and who subsequently met our BSC definition. The proportion of these patients
22
increased with time, i.e. in 1997 17% of patients met the criteria for BSC and 40% of patients did
so in 1999. This suggests that oncologists are recognizing more and more the survival benefit of
treating late stage NSCLC patients with chemotherapy. The majority of the sample of BSC
NSCLC patients was 55 to 74 years of age. However, it is interesting to note that patients over
75 years of age were also being treated with chemotherapy and presumably benefiting from it.
Gridelli reported that patients over 70 years of age with late stage NSCLC who received BSC
plus vinorelbine survived longer and had a better quality of life than those patients who received
BSC only.28
Of the 150 patients, only a small number (17), received second line chemotherapy, which
is not surprising given the fact that the benefit of second line chemotherapy in NSCLC has only
become evident recently.29-32 A small proportion of patients who had second line chemotherapy
received the treatment on average 16 weeks after completion of first line treatment, suggesting
that most of the patients would have had good initial response to first line chemotherapy, and
second line treatment was initiated primarily for subsequent progression. Given the recency of
the evidence indicating a benefit of second line chemotherapy, in the future there may well be an
increasing proportion of patients receiving second line chemotherapy.
Most (93.3%) of the patients in the sample has received either cisplatin or carboplatin in
combination with other drugs. This is in keeping with the American Society of Clinical
Guidelines that suggest that chemotherapy should be a platinum based combination regimen.20
There have been many large randomized trials comparing various chemotherapy regimens for
metastatic NSCLC.
Apart from small differences in tolerability, there were no significant
differences seen in response rates or survival.5,19,32-36
One of the most commonly used
combination regimens in the studies was vinorelbine with a platinum agent. Vinorelbine is the
preferred choice in Canadian centres due to its low drug acquisition cost.
The median survival time during the phase of BSC was 13.8 weeks. This indicates a
substantial proportion of patients tolerated the chemotherapy well and lived a reasonable period
of time following the 10 to 12 weeks of chemotherapy.
The one and two year survival percentages from the date of first chemotherapy were 26.7%
and 8.9% respectively, and the median was 31.8 weeks. Without chemotherapy, approximately
5% of patients with stage IV NSCLC cases live one year.16 Giaccone, in a review of selected
randomized trials conducted between 1994 and 2000, concluded that ‘present chemotherapy can
23
induce a median survival of about 9 months in patients with stage IV and stage III with
malignant pleural effusion, with a 1-year survival of about 35-40%”.22 More recently, Schiller et
al. found that a group of late stage NSCLC patients randomized to four different platinum based
chemotherapy regimens had a median survival time of 8.0 months and a survival rate at one year
of 34%.35 The survival of these patients has improved with chemotherapy.
It is very encouraging to observe that the survival results for our population-based BSC
sample was only slightly lower than the survival reported in the clinical studies. However direct
comparisons with the results from this study and most clinical trials are problematic, as most of
the latter measured survival from date of randomization, whereas the closest comparable date in
this study was date of first chemotherapy. Furthermore, most clinical trials have strict inclusion
criteria, such as good performance status, whereas the present study included all cases. When
one considers that the date of first chemotherapy will be after the randomization date, then the
results of this study would be similar to those reported by Schiller et al. 35
Similar to results reported in recent studies29-32, the BSC patients who received second line
chemotherapy appear to have a significantly better one-year survival than patients who received
only first line chemotherapy, from both time of diagnosis (56% vs. 27%) and time of first
chemotherapy (56% vs. 23%). There wasn’t a significant survival difference between the two
groups from time of last chemotherapy or from BSC date. However, it needs to be noted that
only a small number of patients (n=17) had two lines of chemotherapy, and as previously stated,
the patients who received second line chemotherapy had a relatively long progression free
interval between lines.
In conclusion, this report has provided extensive detail about the chemotherapy those
NSCLC patients in their BSC phase received and information about their survival. Due to the
relatively small sample of patients, there was not enough power to statistically test if there were
differences in survival among patient subgroups. For example, given the relatively recent
introduction of the use of second line chemotherapy treatment for BSC patients there were few
patients who had this treatment, and thus it was not possible to determine if second line
chemotherapy resulted in an increased survival. This question could be addressed by expanding
the study sample to include BSC cases diagnosed since June of 2000. Relevant issues not
examined in this study include what was the response rate to first line chemotherapy, what were
the indications for second line chemotherapy, that is who responded to first line chemotherapy
24
and who did not, and were there any differences in the survival of patients who responded
relative to those that did not. Unfortunately, these questions are not easily answered, as the
databases do not have any information of responder status. In order to answer these questions,
which are of great interests to oncologists, would require an extensive review of the charts to
determine responder status.
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18. Okawara G, Rusthoven J, Newman T, Findlay B, Evans W. Unresected stage III non-smallcell lung cancer. Provincial Lung Cancer Disease Site Group. Cancer Prev Control
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19. Goss GD, Logan DM, Newman TE, Evans WK. Use of vinorelbine in non-small-cell lung
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20. American Society of Clinical Oncology. Clinical practice guidelines for the treatment of
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26. Paesmans M. Benefits of chemotherapy for quality of life in patients with advanced
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27. Rivera MP. Management of patients with advanced non-small-cell lung cancer. Curr Opin
Pulm Med 2001;7(4):247-58.
28. Gridelli C. The ELVIS trial: a phase III Study of single-agent vinorelbine as first-line
treatment in elderly patients with advanced non-small cell lung cancer, Oncologist
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Lee JS, Moore M, Gandara D, Karp D, Vokes E, Kris M, Kim Y, Gamza F, Hammershaimb
L, Tax 320 Non-Small-Cell Lung Cancer Study Group. Randomized phase III trial of
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cancer previously treated with platinum-containing chemotherapy regimens. J Clin Oncol
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2000;2:96-101.
31. Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O’Rourke M, Levitan N, Gressot
L, Vincent M, Burkes R, Coughlin S, Kim Y, Berile J. Prospective randomized trial of
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treated with platinum-based chemotherapy. J Clin Oncol 2000;18:2095-103.
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32. Shepherd FA, Fossella FV, Lyynch T, Armand J-P, Rigas JR, Kris MG. Docetaxel (taxotere)
shows survival and quality-of-life benefits in the second-line treatment of non-small cell lung
cancer: a review of two phase III trials. Semin Oncol 2001;28(Suppl 2):4-9.
33. Haura EB. Treatment of advanced non-small-cell lung cancer: a review of current
randomized clinical trials and an examination of emerging therapies. Cancer Control
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34. Carney DN. Lung cancer – time to move on from chemotherapy. NEJM 2002;346:126-127.
35. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH.
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27
28
Appendix 1. Classification of lung cancer according to morphology
Type
Non-small cell
ICD-0 code
80103
80123
80213
80313
80523
80703
80713
80723
80743
81403
82503
82513
82603
82623
83103
84303
84803
84813
84903
85603
90523
Description
Carcinoma NOS, malignant
Large cell carcinoma
Anaplastic carcinoma
Giant cell carcinoma
Papillary squamous cell carcinoma (papillary epidermoid carcinoma)
Squamous cell carcinoma, malignant
Keratinizing squamous cell carcinoma
Large cell, nonkeratinizing squamous
Squamous cell carcinoma, spindle cell (epidermoid carcinoma, spindle cell)
Adenocarcinoma, malignant
Bronchiolo-alveolar adenocarcinoma
Alveolar adenocarcinoma (alveolar carcinoma)
Papillary adenocarcinoma
Villous adenocarcinoma
Clear cell adenocarcinoma, NOS
Mucoepidermoid carcinoma
Mucinous adenocarcinoma
Mucin-producing adenocarcinoma
Signet ring cell carcinoma (adenocarcinoma)
Adenosquamous carcinoma
Epidethelioid mesothelioma, malignant (epithelioid mesothelioma, NOS)
Small cell
80023
80413
80423
80433
80443
80453
80733
Malignant tumor, small cell type
Small cell carcinoma nos.
Oat cell carcinoma (C34)
Small cell carcinoma, fusiform cell
Intermediate, small cell carcinoma
Small cell - large cell carcinoma
Small cell, nonkeratinizing squamous
Other
80003
80013
80203
80333
81233
82003
Neoplasm nos., malignant
Tumor cells, malignant
Undifferentiated carcinoma
Pseudosarcomatous carcinoma
Basaloid carcinoma
Adenoid cystic carcinoma (adenocyctic carcinoma, cylindroma NOS,
bronchial adenoma cylindroid, edenocarcinoma, cylindroid)
Carcinoid NOS (except appendix: …
Neuro-endocrine carcinoma
Mixed cell carcinoma
Mucinous cystadenoma, borderline malignancy (psedomucinous cystadenoma
borderline malignancy, mucinous tumor NOS or low malignant potential)
Acinar cell carcinoma (acinar cell adenocarcinoma, acinar adenocarcinoma,
acinar carcinoma)
Malignant melanoma NOS
Sarcoma NOS
Fibrosarcoma
Carcinosarcoma NOS
Fibrous mesothelioma
Diffuse lymphoma, small and large cell
Diffuse lymphoma, large cell NOS
Diffuse lymphoma, large cell cleav…
Lymphoma, immunoblastic, NOS p 96123
Monocytoid B-cell lymphoma
82403
82463
83233
84723
85503
87203
88003
88103
89803
90513
96753
96803
96813
96843
97113
29
Appendix 2. Morphology of the trachea, bronchus and lung cancer cases diagnosed in Manitoba,
1997-2000
Type
ICD-O
NSCLC 80103
80123
80213
80313
80523
80703
80713
80723
80743
81403
82503
82513
82603
82623
83103
84303
84803
84813
84903
85603
90523
SCLC
80413
80423
80443
80453
Other
80003
80013
80203
80333
81233
82003
82403
82463
83233
84723
85503
88003
88103
89803
Missing
Total
1997
Count
%
135
18.0
41
5.5
3
0.4
1
0.1
145
19.4
13
1.7
1
0.1
1
0.1
205
27.4
28
3.7
5
0.7
4
0.5
8
1.1
1
0.1
4
0.5
75
10.0
5
0.7
6
0.8
52
7.0
3
0.4
1
0.1
7
0.9
2
0.3
2
0.3
748
100.0
1998
Count
%
172
22.0
35
4.5
2
0.3
2
0.3
1
0.1
137
17.5
17
2.2
1
0.1
0
211
26.9
21
2.7
1
0.1
7
0.9
0
3
0.4
1
0.1
3
0.4
16
2.0
0
2
0.3
0
85
10.9
4
0.5
2
0.3
1
0.1
49
6.3
0
0
1
0.1
0
0
6
0.8
1
0.1
0
0
0
0
1
0.1
1
0.1
0
783
100.0
1999
Count
%
169
22.2
22
2.9
4
0.5
123
16.2
19
2.5
1
0.1
193
25.4
33
4.3
3
0.4
1
0.1
2
0.3
1
0.1
13
1.7
1
0.1
5
0.7
89
11.7
3
0.4
3
0.4
4
0.5
58
7.6
1
0.1
1
0.1
1
0.1
6
0.8
1
0.1
1
0.1
1
0.1
1
0.1
760
100.0
30
2000
Count
%
163
21.3
32
4.2
3
0.4
2
0.3
129
16.9
16
2.1
2
0.3
202
26.4
47
6.1
3
0.4
5
0.7
1
0.1
7
0.9
1
0.1
81
10.6
1
0.1
5
0.7
2
0.3
49
6.4
1
0.1
7
0.9
3
0.4
1
0.1
1
0.1
1
0.1
765
100.0
Total
Count
%
639
20.9
130
4.3
5
0.2
11
0.4
2
0.1
534
17.5
65
2.1
5
0.2
1
811
26.5
129
4.2
1
18
0.6
1
5
0.2
1
8
0.3
42
1.4
3
0.1
18
0.6
1
330
10.8
13
0.4
16
0.5
7
0.2
208
6.8
1
4
0.1
2
0.1
1
1
26
0.9
6
0.2
1
1
1
2
0.1
1
4
0.1
1
3056 100.0
Appendix 3.1 Distribution of chemotherapy according to schedule (line and cycle) for BSC NSCLC cases
Drugs
1
Cycle 1
Cycle 2
Cycle 3
Cycle4
Cycle 5
Cycle 6
Cycle 7
Cycle 8
Cycle 9
Cycle10
N
N
N
N
N
N
N
%
N
%
N
%
N
%
N
%
%
%
%
%
%
%
Total
Line 1
CIS + VIN
CIS + ETO
CIS + ETO + ADR
CIS + GEM
CIS + PAC
CAR + PAC
CAR + VIN
CAR + ETO
CAR + GEM
VIN
Other
48
27
-1
1
29
28
7
-7
3
31.8
17.9
-0.7
0.7
19.2
18.5
4.6
-4.6
2.0
36
20
1
1
1
28
27
5
-4
2
28.8
16.0
0.8
0.8
0.8
22.4
21.6
4.0
-3.2
1.6
28
13
1
3
-16
26
4
-4
--
29.5
13.7
1.1
3.2
-16.8
27.4
4.2
-4.2
--
15
8
1
3
-9
17
3
-3
1
25.0
13.3
1.7
5.0
-15.0
28.3
5.0
-5.0
1.7
8
5
1
--8
8
-1
2
--
24.2
15.2
3.0
--24.2
24.2
-3.0
6.1
--
4
4
1
--8
7
-1
2
--
14.8
14.8
3.7
--29.6
25.9
-3.7
7.4
--
------2
1
--1
------50.0
25.0
--25.0
-------1
--1
-------50.0
--50.0
-------1
----
-------100
----
-------1
----
-------100
----
139
77
5
8
2
98
115
23
2
22
8
27.9
15.4
1.0
1.6
0.4
19.6
23.0
4.6
0.4
4.4
1.6
Total2
151
100
125
100
95
100
60
100
33
100
27
100
4
100
2
100
1
100
1
100
499
100
-----------
-----------
-----------
-----------
-----------
-----------
-----------
12 22.2
2
3.7
4
7.4
6 11.1
5
9.3
3
5.6
1
1.9
14 25.9
3
5.6
4
7.4
Line 2
CIS + ETO
CIS + GEM
CIS + VIN
CAR + PAC
CAR + VIN
CAR + ETO + ADR
DOC
VIN
Other
3
2
1
1
2
-1
4
3
--
17.6
11.8
5.9
5.9
11.8
-5.9
23.5
17.6
--
2
-1
1
1
1
-3
-1
20.0
-10.0
10.0
10.0
10.0
-30.0
-10.0
2
-1
1
1
1
-3
-1
20.0
-10.0
10.0
10.0
10.0
-30.0
-10.0
2
-1
1
1
1
-2
-1
22.2
-11.1
11.1
11.1
11.1
40.0
--20.0
---20.0
-20.0
1
--1
---1
---
33.3
--33.3
---
22.2
-11.1
2
--1
---1
-1
33.3
---
-----------
Total
17
100
10
100
10
100
9
100
5
100
3
100
--
--
--
--
--
--
--
--
54
100
--
--
--
--
--
--
--
--
1
100
Line 3
DOC
1
100
--
--
--
--
--
--
--
--
--
--
1. ADR: adriamycin, BLE: bleomycin, CAR: carboplatin, CIS: cisplatin, DOC: docetaxel, ETO: etoposide, GEM: gemcitabine, PAC: paclitaxel, VIN: vinorelbine
2. Two patients (one on cycle 1 and one on cycle 2) had their drugs changed on the same day they started treatment, which is why the sums for cycle 1 and 2 are higher than those
of other tables
31
Appendix 3.2 Distribution of chemotherapy according to schedule (line and cycle) for stage IIIb BSC NSCLC cases
Drugs1
Cycle 1
Cycle 2
Cycle 3
Cycle4
Cycle 5
Cycle 6
Cycle 7
Cycle 8
Cycle 9
Cycle10
N
N
N
N
N
N
N
%
N
%
N
%
N
%
N
%
14.3
14.3
---
---
---
---
---
---
---
---
34
22
31.8
20.6
28.6
42.9
---
---
---
---
---
---
---
---
19
32
17.8
29.9
100
--
--
--
--
--
--
--
--
107
100
%
%
%
%
%
%
Total
:Line 1
CIS + VIN
CIS + ETO
CAR + PAC
CAR + VIN
Total
12
9
6
6
33
36.4
27.3
18.2
18.2
100
10
6
5
5
26
38.5
23.1
19.2
19.2
100
7
3
3
8
21
33.3
14.3
14.3
38.1
100
3
2
1
6
12
25.0
16.7
8.3
50.0
100
1
1
2
4
8
12.5
12.5
25.0
50.0
100
1
1
2
3
7
Line 2
CIS + ETO
CIS + GEM
CIS + VIN
CAR + VIN
CAR + ETO + ADR
VIN
Total
1
1
1
2
-1
1
7
14.3
14.3
14.3
28.6
-14.3
14.3
100
1
-1
1
1
--4
25.0
-25.0
25.0
25.0
--100
1
-1
1
1
--4
25.0
-25.0
25.0
25.0
--100
1
-1
1
1
--4
25.0
-25.0
25.0
25.0
--100
1
------1
100
-----
------
------
------
------
------
------
------
------
------
------
5
1
4
5
3
25.0
5.0
20.0
25.0
15.0
---
---
---
---
---
---
---
---
---
---
---
1
1
5.0
5.0
100
--
--
--
--
--
--
--
--
--
--
20
100
1. ADR: adriamycin, BLE: bleomycin, CAR: carboplatin, CIS: cisplatin, ETO: etoposide, GEM: gemcitabine, PAC: paclitaxel, VIN: vinorelbine
of other tables
32
Appendix 3.3 Distribution of chemotherapy according to schedule (line and cycle) for stage IV BSC NSCLC cases
Drugs
1
Cycle 1
Cycle 2
Cycle 3
Cycle4
Cycle 5
Cycle 6
Cycle 7
Cycle 8
Cycle 9
Cycle10
N
N
N
N
N
N
N
%
N
%
N
%
N
%
N
%
------2
1
--1
4
------50.0
25.0
--25.0
-------50.0
--50.0
105
55
5
8
2
79
83
23
2
22
8
26.8
14.0
1.3
2.0
0.5
20.2
21.2
5.9
0.5
5.6
2.0
100
-------1
---1
-------100
----
100
-------1
---1
-------100
----
100
-------1
--1
2
100
392
100
33.3
--
---
---
---
---
---
---
---
---
7 20.6
1 2.9
33.3
33.3
---
-----
-----
-----
-----
-----
-----
-----
-----
6 17.6
14 41.2
2 5.9
4 11.8
100
--
--
--
--
--
--
--
--
34
--
--
--
--
--
--
--
--
%
%
%
%
%
%
Total
Line 1
CIS + VIN
CIS + ETO
CIS + ETO + ADR
CIS + GEM
CIS + PAC
CAR + PAC
CAR + VIN
CAR + ETO
CAR + GEM
VIN
Other
Total
36
18
-1
1
23
22
7
-7
3
118
30.5
15.3
-0.8
0.8
19.5
18.6
5.9
-5.9
2.5
100
26
14
1
1
1
23
22
5
-4
2
99
26.3
14.1
1.0
1.0
1.0
23.2
22.2
5.1
-4.0
2.0
100
21
10
1
3
-13
18
4
-4
-74
28.4
13.5
1.4
4.1
-17.6
24.3
5.4
-5.4
-100
12
6
1
3
-8
11
3
-3
1
48
25.0
12.5
2.1
6.3
-16.7
22.9
6.3
-6.3
2.1
100
7
4
1
--6
4
-1
2
-25
28.0
16.0
4.0
--24.0
16.0
-4.0
8.0
-100
3
3
1
--6
4
-1
2
-20
15.0
15.0
5.0
--30.0
20.0
-5.0
10.0
-100
Line 2
CIS + ETO
CIS + GEM
CAR + PAC
DOC
VIN
Other
Total
2
1
1
4
2
-10
20.0
10.0
10.0
40.0
20.0
-100
1
-1
3
-1
6
16.7
-16.7
50.0
-16.7
100
1
-1
3
-1
6
16.7
-16.7
50.0
-16.7
100
1
-1
2
-1
5
20.0
-20.0
40.0
-20.0
100
1
-1
1
-1
4
25.0
-25.0
25.0
-25.0
100
1
-1
1
--3
100
Line 3
DOC
1
100
--
--
--
--
--
--
--
--
--
--
1 100
1. ADR: adriamycin, BLE: bleomycin, CAR: carboplatin, CIS: cisplatin, DOC: docetaxel, ETO: etoposide, GEM: gemcitabine, PAC: paclitaxel, VIN: vinorelbine
of other tables
33
Appendix 3.4 First line chemotherapy for the 17 stage IIIb and IV BSC NSCLC cases who received second line chemotherapy
Drugs
1
Cycle 1
Cycle 2
Cycle 3
Cycle4
Cycle 5
Cycle 6
Cycle 7
Cycle 8
Cycle 9
Cycle10
N
N
N
N
N
N
N
%
N
%
N
%
N
%
N
%
20.0
-20.0
20.0
-----
-----
-----
-----
-----
-----
-----
-----
6
1
7
5
9.5
1.6
11.1
7.9
Stage IV
--1 20.0
--20.0
1
-----
-----
-----
-----
-----
-----
-----
-----
-----
11.1
7.9
4.8
11.1
4.8
3.2
--
--
--
--
--
--
--
--
7
5
3
7
3
2
63
%
%
%
%
%
%
Total
Stage IIIb
CIS + VIN
CIS + ETO
CAR + PAC
CAR + VIN
CIS + VIN
CIS + ETO
CIS + GEM
CAR + PAC
CAR + VIN
VIN
Total2
2
1
3
1
11.8
5.9
17.6
5.9
4
1
1
3
-1
17
23.5
5.9
5.9
17.6
-5.9
100
2
1
3
1
12.5
6.3
18.8
6.3
2
1
1
3
1
1
16
12.5
6.3
6.3
18.8
6.3
6.3
100
1
-1
1
10.0
-10.0
10.0
2
1
1
1
1
1
10
20.0
10.0
10.0
10.0
10.0
10.0
100
1
-1
1
11.1
-11.1
11.1
2
1
1
1
1
-9
22.2
11.1
11.1
11.1
11.1
-100
1
-1
1
16.7
-16.7
16.7
1
1
-1
--6
16.7
16.7
-16.7
--100
1
-1
1
5
1. CAR: carboplatin, CIS: cisplatin, ETO: etoposide, GEM: gemcitabine, PAC: paclitaxel, VIN: vinorelbine
34
100
100
Appendix 3.5 First and second line chemotherapy for the stage IV BSC NSCLC cases who received second line chemotherapy
Drugs
1
Cycle 1
Cycle 2
Cycle 3
Cycle4
Cycle 5
Cycle 6
Cycle 7
Cycle 8
Cycle 9
Cycle10
N
N
N
N
N
N
N
%
N
%
N
%
N
%
N
%
%
%
%
%
%
%
Total
Line 1
CAR + PAC
CIS + GEM
GEM + VIN
Total
1
1
-2
50.0
50.0
-100
1
-1
2
50.0
-50.0
100
--1
1
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
2
40.0
---
---
---
---
---
---
---
---
20.0
40.0
--
--
--
--
--
--
--
--
1
2
5
-100
---
---
---
---
Line 2
-----
100
--
--
--
--
--
1. CAR: carboplatin, CIS: cisplatin, GEM: gemcitabine, PAC: paclitaxel, VIN: vinorelbine
35
--
100

Survival of Stage 3,4 Non-Small-Cell Lung Cancer

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