Patient characteristics.
Between the two groups, no statistical difference was confirmed in the age, TNM stage and operative procedure (Tabel 1).
Table 1. Patient characteristics
|
PEG(-)
|
PEG(+)
|
P- value
|
Number of patients
|
49
|
36
|
|
Age at the operation (y/o)
|
51.6 ± 11.8
|
51.7 ± 9.7
|
0.948
|
Subtype
|
|
|
|
ER(+), PgR(+), HER2 (-)
|
48
|
36
|
0.024
|
ER(-), PgR(-), HER2 (-)
|
1
|
0
|
|
Stage
|
|
|
|
I
|
23
|
9
|
0.199
|
II
|
26
|
27
|
|
Operative procedure
|
|
|
|
Total mastectomy
|
29
|
27
|
0.140
|
Partial mastectomy
|
20
|
9
|
|
Tabel 2 indicates the age distribution of the two groups. Neither the mean age nor the age distribution showed statistical difference between the two groups. Those mean that no significant factor that would influence the chemotherapeutic course and the onset of adverse events was find out.
Table 2
The age distribution of the patients enrolled
|
Age distribution
|
|
30s
|
40s
|
50s
|
60s
|
70s
|
PEG(-)
|
9
|
15
|
9
|
12
|
4
|
PEG(+)
|
2
|
18
|
7
|
9
|
0
|
Although TC chemotherapy commonly applied to the hormonal-positive and HER2-negative patient (9), PEG(-) group included one patient of hormonal-negative and HER2-negative (Tabel 1).
Adverse events
Major adverse events are summarized in Table 3.
Table 3
Summary of adverse events
|
PEG(-)
|
PEG(+)
|
|
Symptoms
|
Grade 1 and 2
|
Grade 3 and 4
|
Grade 1 and 2
|
Grade 3 and 4
|
P-value
|
Neutrophil count decreased
|
2
|
21
|
5
|
6
|
0.0238
|
Fever
|
11
|
0
|
5
|
0
|
N.A.
|
Neuralgia
|
19
|
0
|
25
|
0
|
N.A.
|
Rash acneiform
|
35
|
2
|
29
|
0
|
0.4998
|
Nausea
|
15
|
0
|
17
|
1
|
1.0000
|
Diarrhea
|
16
|
0
|
20
|
1
|
1.0000
|
Anorexia
|
7
|
1
|
10
|
1
|
1.0000
|
Arthralgia and myalgia
|
14
|
0
|
3
|
1
|
0.2222
|
Dysgeusia
|
13
|
0
|
16
|
0
|
N.A.
|
Fatigue
|
32
|
0
|
18
|
1
|
0.3725
|
Edema
|
20
|
0
|
20
|
0
|
N.A.
|
Statistical analysis could not be performed on the symptoms of neuralgia, dysgeusia and edema, because those categories included zero-factors in the both groups of PEG(-) and PEG(+). N.A.: not available |
The number of the patients that were diagnosed as “neutrophil count discount” ranging with Grade 3 to 4 was 21 and 6 in PEG(-) and PEG(+), respectively (P = 0.0238). The odds ratio for the onset of “neutrophil count decreased” ranging with Grade 3 to 4 of PEG(+) compared to that of PEG(-) was 0.1143 (95% confidence interval, 0.0175–0.7446). The number of patients who had experienced the hospitalization for treatments of the adverse symptoms was 4 and 1 in PEG(-) and PEG(+), respectively (P = 0.5645). There were 3 patients affected with FN only in PEG(-) group. The median neutrophil count (range) on the admission of those 3 patients was 32 (18–234) /mL. The median duration (range) of the hospital stay was 6 (5–8) and 5 (5–7) days in PEG(-) and PEG(+), respectively. The other reasons for the hospitalization included general fatigue, nausea and anorexia. The two groups contained one by one patient who was admitted 3 to 4 times.
RDI and laboratory data
Table 4 demonstrate the detail data for the calculation of RDIs of each agent. As expected, the RDIs of PEG(+) was significantly higher than those of PEG(-). And the P values of docetaxel and cyclophosphamide are 0.0074 and 0.0331, respectively. Effectiveness of pegfilgrastim for keeping higher RDI was clearly verified.
Table 4
The detail data for the calculation of dose intensity
|
Docetaxel
|
Cyclophosphamide
|
PEG(-)
|
PEG(+)
|
PEG(-)
|
PEG(+)
|
Actual Dose (mg)
|
433.8 ± 58.4
|
449.1 ± 46.0
|
3489.7 ± 453.3
|
3608.0 ± 367.9
|
Actual Time (week)
|
9.7 ± 1.3
|
9.2 ± 0.6
|
9.7 ± 1.3
|
9.2 ± 0.6
|
Actual dose intensity (mg/week)
|
45.2 ± 8.8
|
48.9 ± 6.8
|
364.2 ± 69.8
|
392.9 ± 54.6
|
Standard Dose (mg)
|
459.9 ± 37.4
|
460.1 ± 34.3
|
3679.6 ± 299.7
|
3681.0 ± 275.1
|
Standard Time (week)
|
9
|
9
|
9
|
9
|
Standard dose intensity (mg/week)
|
51.1 ± 4.1
|
51.1 ± 3.8
|
408.8 ± 33.3
|
409.0 ± 30.5
|
Relative dose intensity (%)
|
87.7 ± 14.0*
|
94.5 ± 8.6†
|
88.2 ± 14.0*
|
94.8 ± 8.3†
|
Both Actual Dose and Standard Dose indicate the total amount of the agents that were administered through the 4 courses of chemotherapy. Both Actual Time and Standard time was decided as the interval from the day1 of the 1st course to the same day1 of the 4th course. The values of the table are expressed by mean with standard deviation excluding “Standard Time.” The significant difference was identified in “Relative dose intensity” between PEG(-) and PEG(+). P value of the each pair, * and †, in Docetaxel and Cyclophosphamide are 0.0074 and 0.0331, respectively.
The trend of laboratory tests during the TC chemotherapy are demonstrated in Fig. 1. The factors evaluated included neutrophil, platelet, hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatine (Fig. 1).
Interestingly, the counts of neutrophils of PEG(-) showed significantly higher number than those of PEG(+) in each cycle and that increased significantly in each cycle. The counts of lymphocyte decreased gradually in each cycle, however no significant difference between the two group was recognized excluding that of the 1st cycle. The hemoglobin level during the chemotherapy of PEG(+) decreased gradually and the difference between the 2 groups at 4th cycle was 1.02 g/dL with statistical significancy. The hemoglobin level of the 2 group at the 4th cycle was 11.92 and 10.90 g/dL.
Disease- free survival
A total of 13 patients, which consist of 10 in PEG(-) and 3 in PEG(+), experienced the recurrence of the primary breast cancer. And 2 patients expired due to the recurrence. Six and 2 patients were lost from the follow-up in PEG(-) and PEG(+), respectively. The mean DFS period of each group and the Kaplan-Meier curve were demonstrated in Table 5 and Fig. 2, respectively. Because the number of events were so small that the difference of disease-free survival rates of each group could not reach the significant level.
Table 5
|
Disease-free survival period
(mean ± standard error)
|
95% confidence interval
|
Log-rank test (P valure)
|
PEG(-)
|
9.92 ± 0.40
|
9.12–10.72
|
0.7773
|
PEG(+)
|
6.32 ± 0.31
|
5.69–6.94
|
The unit for the survival period and 95% confidence interval is year.
Solid and Dotted curves indicate PEG(-) and PEG(+), respectively. No significant difference between the two groups was recognized with log-rank test