1. CALGB A Randomized Trial of Dose-Dense vs Conventionally Scheduled and Sequential vs Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer
Citron M, et al. J Clin Oncol. 2003;21:

2. C9741—Protocol 2X2 Factorial Design q3wk q2wk + Filgrastim SEQUENTIAL
24 wk “Seq Q2”
36 wk “Seq Q3”
CONCURRENT
16 wk “Con Q2”
24 wk “Con Q3”
Doxorubicin 60 mg/m2
Cyclophosphamide 600 mg/m2
Paclitaxel 175 mg/m2 over 3 h
With Permission from Citron M, et al. J Clin Oncol. 2003;21:

3. C9741—Major Toxicities Seq q3 Seq q2 Con q3 Con q2 No. treated 484 493
501
495
No. with detailed data
103
101
104
Granulocytes < 0.5/µL
24% 3%
43% 9%
Febrile neutropenia, hospitalized 2% 6%
Red cell transfusion 0% 4%
13%
Platelet transfusion
Neurologic: severe sensory loss or motor weakness 5% 7%
Citron M, et al. J Clin Oncol. 2003;21: Erratum published in J Clin Oncol, 2003;21:2226.

4. C9741—Disease-Free Survival by Dose Density
By Density
1.0
q 2
0.8
q 3
0.6
Proportion Disease-Free
q2wk
N = 988
Events = 136
q3wk
N = 985
Events = 179
0.4
0.2
RR = 0.74; P = .010
0.0 1 2 3 4
Years from Study Entry
With permission from Citron M, et al. J Clin Oncol. 2003;21:

5. Cox Model—Retrospective Analysis of Dose Density (q2) Therapy by ER Status in C9741
ER = estrogen receptor; DFS = disease-free survival; OS = overall survival Courtesy of Marc Citron, MD. With permission from C. Hudis, MD.

6. C9741—DFS by Dose Density at Median 5-Year Follow-up
1.0
0.9
q2wk
0.8
0.7
q3wk
0.6
Disease-Free Survival
0.5
0.4
0.3
Q2 n = 988 Events = 230
Q3 n = 984 Events = 278
P = .012
0.2
0.1
0.0 1 2 3 4 5 6 7
Year
Hudis C, et al San Antonio Breast Cancer Symposium. Abstract 41. With permission from C. Hudis, MD.

7. C9741—DFS by ER Status and Dose Density at 5-Year Median
1.0
0.9
ER+ q2wk
0.8
ER+ q3wk
0.7
0.6
ER- q2wk
Disease-Free Survival
0.5
ER- q3wk
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7
Year
ER+ q2 n = 636 Events = ER- q2 n = 336 Events = 99
ER+ q3 n = 639 Events = ER- q3 n = 327 Events = 127
P = NS
P = .014
ER = estrogen receptors With permission from Hudis C, et al San Antonio Breast Cancer Symposium. Abstract 41.

8. Dose-Dense Chemotherapy-Induced Pulmonary Toxicity
Courtesy of Marc Citron, MD.

9. Accelerated vs Standard FEC Regimen GONO-MIG1 Protocol
FEC14 = q2wk (w/G-CSF) for 10 wk
FEC21 = q3wk for 15 wk
F = fluorouracil 600 mg/m2
E = epirubicin 60 mg/m2
C = cyclophosphamide 600 mg/m2
Accrued N = 1214
10.4 yr median follow-up
359 events
Venturini M, et al. J Natl Cancer Inst. 2005;97:

10. Accelerated vs Standard FEC Regimen GONO-MIG1 Results
No significant differences in:
• Event-free survival
- HR for FEC14/FEC21 = 0.88, 95% CI (0.71–1.08) P =.219
• Risk of death
- HR for FEC14/FEC21 = 0.87, 95% CI (0.67–1.13) P = .293
Toxicity
FEC14
FEC21
Asthenia
36%
29%
Anemia
38%
19%
Bone pain
33% 4%
Leukopenia
12%
45%
FEC = fluorouracil, epirubicin, cyclophosphamide; HR = hazard ratio. Venturini M, et al. J Natl Cancer Inst. 2005;97:

11. GONO-MIG1—Accelerated FEC Provides No Significant Benefit for HER2 Negative
EFS OS
HER2 negative
HER2 negative
92%
100
100 90
82% 90
91% 80 80
81% 70 70 60 60 50 50
% Event Free
% SURVIVAL 40 40
FEC21
FEC21 30 30 20 20
HR = 0.91 (0.65–1.27)
P = .57 10
FEC14
HR = 0.79 (0.49–1.28)
p = .34 10
FEC14 1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10
Years
Years
No. at risk
No. at risk
FEC14
320
309
286
266
235
179
105 52 16 1
FEC14
320
318
314
308
297
244
161 92 31
FEC21
308
297
281
247
227
178
107 52 16
FEC21
308
307
303
296
286
233
160 92 37 1
GONO-MIG1 = Gruppo Oncologico Nord-Ovest-Mammella Intergruppo; FEC = fluorouracil, epirubicin, cyclophosphamide;
EFS = event-free survival; OS = overall survival.
With permission from Del Mastro L, et al. Br J Cancer. 2005;93:7-14.

12. GONO-MIG1—Accelerated FEC Showed Trend Toward Benefit for HER2 Positive
EFS OS
HER2 positive
HER2 positive
100
100
90%
FEC21 90 90
78%
FEC21 80 80 70
FEC14 70
75% 60
FEC14
63% 60 50 50
Eent Free (%)
Survival (%) 40 40 30 30 20 20
HR = 0.54 (0.27–1.11)
P = .092
HR = 0.59 (0.25–1.37)
P = .22 10 10 1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10
Years
Years
No. at risk
No. at risk
FEC14 50 50 44 39 33 27 15 10 5
FEC14 50 50 50 47 46 39 23 14 5
FEC21 53 48 41 32 31 23 16 7 2
FEC21 53 52 47 45 42 33 20 9 4
GONO-MIG1 = Gruppo Oncologico Nord-Ovest-Mammella Intergruppo; FEC = fluorouracil, epirubicin, cyclophosphamide;
EFS = event-free survival; OS = overall survival.
With permission from Del Mastro L, et al. Br J Cancer. 2005;93:7-14.