TAXTOX – a retrospective study regarding the side effects of docetaxel given as part of the adjuvant treatment to patients with primary breast cancer in Denmark from 2007 to 2009

Figures & data

Table I. Patients characteristics.

Patients characteristic	Numbers (N) 1143	(%) 100
Age
<31	20	1.7
31–40	102	8.9
41–50	389	34.0
51–60	501	43.8
61–70	121	10.6
71–80	9	0.8
81–90	1	0.1
Nodal status
0	433	37.9
1–3	482	42.2
>3	222	19.4
Unknown	6	0.5
Size
0–20 mm	564	49.3
21–50 mm	528	46.2
>50 mm	42	3.7
Unknown	9	0.8
Malignancy grade
Grad I	179	15.7
Grad II	473	41.4
Grad III	410	35.9
Non-ductal	81	7.1
ER status
Negative	368	32.2
Positive	767	67.1
Unknown	8	0.7

Figure 1. Cause of treatment termination - after cycle 3 and before cycle 6. E=epirubicin, C=cyclophosfamide, D=docetaxel.

Table II. The maximum incidence of the recorded and non-recorded non-hematological side-effects.

	Grade 0	Grade 1	Grade 2	Grade 3	Grade 4	Overall 1–4	Data not available
Stomatitis	175 (15.3%)	230 (20.1%)	606 (53.0%)	14 (1.2%)	0	850 (74.3%)	118 (10.3%)
Diarrhea	213 (18.6%)	130 (11.4%)	71 (6.2%)	14 (1.2%)	2 (0.2%)	217 (19.0%)	713 (62.4%)
Muscles and joint pain	42 (3.7%)	188 (16.4%)	343 (30.0%)	76 (6.6%)	3 (0.3%)	604 (53.3%)	491 (43.0%)
Neuropathy	520 (45.5%)	160 (14.0%)	209 (18.3%)	30 (2.6%)	1 (0.1%)	400 (35.0%)	223 (19.5%)
Skin rash*	194 (17.0%)	151 (13.2%)	121 (10.6%)	17 (1.5%)	—	289 (25.3%)	660 (57.7%)
Nail problems†	128 (11.2%)	212 (18.5%)	107 (9.4%)	—	—	319 (27.9%)	696 (60.9%)
Vomiting	593 (51.9%)	170 (14.9%)	131 (11.5%)	21 (1.8%)	2 (0.2%)	324 (28.3%)	226 (19.8%)
Nausea	305 (26.7%)	350 (30.6%)	295 (25.8%)	26 (2.3%)	3 (0.3%)	674 (59.0%)	164 (14.4%)
Fatigue	42 (3.7%)	272 (23.8%)	195 (17.1%)	25 (2.2%)	2 (0.2%)	494 (43.2%)	607 (53.1%)
Edema‡	166 (14.5%)	121 (10.6%)	64 (5.6%)	4 (0.3%)	—	189 (16.5%)	788 (68.9%)
Others	246 (21.5%)	264 (23.1%)	143 (12.5%)	20 (1.7%)	4 (0.3%)	431 (37.7%)	466 (40.8%)

According to NCI CTC version 2.0 the highest grade of side-effects regarding nails† is grade 2, skin* grade 3 and Edema‡ grade 3.

Table III. Impact of growth factor on FN in the different cohorts – 2007 vs. 2008.

	2007 without G-CSF		2008 with G-CSF
	Patients n =	Numbers of FN	Patients n =	Numbers of FN
1 EC	654	28 (4.3%)	489	16 (3.2%)
2 EC	654	8 (1.2%)	489	6 (1.2%)
3 EC	654	4 (0.6%)	489	10 (2.0%)
1 D	654	100 (15.3%)	489	18 (3.7%)
2 D	620	19 (3.1%)	476	5 (1.0%)
3 D	599	21 (3.5%)	463	4 (0.8%)

EC, Epirubicin and Cyclophofamide; D, Docetaxel.

Table IV. Non-hematological side-effects of adjuvant taxane-containing treatment for early breast cancer, reported in the literature.

Non-hematological side-effect	All grade 1–4%	Grade 1 + 2%	Grade 3 + 4%
Stomatitis literature	34–73.7 [15,17,20]	1–71 [10,15,17,20]	1.0–9 [8,12–21]
Diarrhea literature	35.2 [17]	31.4 [17]	1.5–4 [15,17–19,21]
Myalgia* literature	23.4–33 [14,15,17]	20.6–32 [14,15,17]	0.8–12.4 [9,11,12,14,15,17–19,21]
Neuropathy literature	18–49.7 [10,13,17,20,21]	15–49.5 [10,13,17,20,21]	0–18 [9–14,17–21]
Skin rash literature	26.5–56.5 [17,20]	25.7–55.6 [17,20]	0.3–3.3 [17–21]
Nail problems literature†	18.5–55.9 [17,20]	18.1–55.9 [17,20]	0.4–10.3 [8,17]
Vomiting literature	10.7–44.5 [15,17,20]	10.2–40.2 [15,17,20]	0.5–11.2 [8,12,14,15,17–20]
Edema literature	28–63.2 [15,17,20,21]	27.9–61.6 [15,17,20,21]	0.1–4.8 [8,15,17–21]
Nausea literature‡	0–80.5 [15,17,21]	3–75.4 [10,15,17]	2.0–11.2 [8,12,14,15,17–19]
Allergic reaction	0.6–13.7 [10,13,17,18,20]	0.5–11.7 [10,13,18,20]	0.1–2.0 [10–13,17,18,20,21]
Fatigue literature	78–91.2 [15,17,20]	69.6–83 [15,17,20]	1.1–22 [12,14,15,17–21]

Numbers in brackets refer to the studies reporting the side effect. *Included in some of the reported numbers is also atralgia, †According to NCI CTC version 2.0 the highest grade of side-effect regarding Nails is grade 2, ‡Registered as grade 2 + 3 + 4 in CALBG 9344.

Table V. Hematological side-effects of adjuvant taxane-containing treatment for early breast cancer, reported in the literature and in this study DBCG 07/08.

Study (ref) A. Toxicity grade scale definition B. Definition of FN: Fever and…	N	Treatment regimes	FN
MDACC [9] A. Not stated B. Not stated	265	4 P*(250)+4 FAC(500,50,500)	17%
CALBG 9344 [10] A. Not stated B. Not stated	1570	4 AC(60/75/90†, 600) + 4P*(175)	Not stated
NSABP B-28 [11] A. Not stated B. Not stated	1531	4 AC(60,600) + 4P*†(225)	P-cycles alone 3%
HeCOG [12] A. WHO B. Not stated	523 540	4EP‡ (83,187) + 3CMF(840,57,840) 3E(110) + 3P(250) + 3 CMF	5.9% 4.6%
ECTO [6] A. NCI CTC version 2.0 B. ANC < 0.5	451	4 A(60)P(200) + 4 CMF(600,40,600)	7.7%
GEICAM 9906 [7] A. NCI CTC 1.0 B. Not stated	614	4 FEC(600,90,600) + 8P*(100)	5.1%
US Oncology [8,9] A. NCI CTC version 1.0 B. ANC < 0.5	506	4 DC(75,600)	5%
PACS 01 [14] A. WHO B. Not stated	996	3 FEC(500,100,500) + 3 D*(100)	11.2%
BCIRG 001[10] A. NCI CTC 1.0/2.0) B. ANC < 1.0	745	6 D*†AC(75,50,500)	28.8%
ECOG 2197 [11] A. NCI CTC 2.0 B. ANC < 1.0	1441	4 AD*† (60,60)	17%
UK TACT study (CRUK01/001) [12] A. NCI CTC 2.0 B. ANC < 1.0	2073	4FEC(600,60,600) + 4 D†(100)	7%
FINHER [13] A. NCI CTC 2.0 B. ANC < 1.0	502	3D*(80/100) + 3 EC (600,60,600)	(100) = 36.9% (80) = 14.9%
BIG 2-98 [15] A. NCI CTC 1.0 B. ANC < 1.0	960 959	3A (75) + 3 D(100) + 3 CMF (100,40,600) 4A(50)D‡ (75) + 3 CMF	12% 16%
DBCG 07/08 A. NCI CTC 2.0 B. Leuco < 1.5 and/or ANC < 1.0	654 489	3 CE(90) + 3 D(100) 2007 3 CE(90) + 3 D‡(100) 2008	25% 10%

A, doxorubicin; C, cyclophosfamide; E, epirubicin; M, methotrexate; F, fluorouracil; P, paclitaxel; D, docetaxel.

*Secondary G-CSF after 1 FN, †Prophylactics antibiotic used secondary, ‡Primary G-CFS.

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