Prognostic value of chemotherapy-induced hematological toxicity in metastatic colorectal cancer patients

Table 1 Patient characteristics according to hematological toxicity in 399 consecutive patients with metastatic colorectal cancer n (%)

	All (n = 399)		Anemia (n= 397)				Neutropenia (n= 396)				Thrombopenia (n= 396)
			No (n= 33)		Yes (n= 364)		P	No (n= 114)		Yes (n= 282)		P	No (n= 163)		Yes (n= 233)		P
Mean ± SD	65 ± 11		66.5 ± 10		64.9 ± 11.1		0.508	69 ± 11.7		63.5 ± 10.4		< 10-4	67.4 ± 11.2		63.4 ± 10.7		< 10-3
Median (min-max)	65.5 (24.7-90.7)		67.8 (50-85.8)		65.5 (24.7-90.7)			69.6 (44.4-90.7)		63.5 (24.7-85.8)			67.5 (24.7-90.7)		63.5 (28.2-88.2)
Origin							0.994					0.622					0.392
Colon	314	(79.1)	26	(78.8)	287	(78.8)		88	(77.2)	224	(79.4)		125	(76.7)	187	(80.3)
Rectum	85	(21.4)	7	(21.2)	77	(21.2)		26	(22.8)	58	(20.6)		38	(23.3)	46	(19.7)
Gender							0.554					0.106					0.559
Male	213	(53.4)	16	(48.5)	196	(53.8)		68	(59.6)	143	(50.7)		84	(51.5)	127	(54.5)
Female	186	(46.6)	17	(51.5)	168	(46.2)		46	(40.4)	139	(49.3)		79	(48.5)	106	(45.5)
WHO PS							0.233					0.024					0.139
0	134	(47.9)	16	(72.7)	117	(45.5)		26	(32.1)	107	(54.0)		49	(40.2)	84	(53.5)
1	102	(36.4)	5	(22.7)	97	(37.7)		34	(42.0)	68	(34.3)		52	(42.6)	50	(31.8)
2	33	(11.8)	1	(4.5)	32	(12.5)		16	(19.8)	17	(8.6)		14	(11.5)	19	(12.1)
3	8	(2.9)	0	(0)	8	(3.1)		3	(3.7)	5	(2.5)		5	(4.1)	3	(1.9)
4	3	(1.1)	0	(0)	3	(1.2)		2	(2.5)	1	(0.5)		2	(1.6)	1	(0.6)
Missing	119		11		107			33		84			41		76
Metastatic sites							0.264					0.646					0.774
Single	241	(60.6)	23	(69.7)	217	(59.8)		71	(62.3)	168	(59.8)		100	(61.3)	139	(59.9)
Multiple	157	(39.4)	10	(30.3)	146	(40.2)		43	(37.7)	113	(40.2)		63	(38.7)	93	(40.1)
Missing	1		0		1			0		1			0		1
Leucocyte count							0.151					0.337					0.501
< 10000	219	(74.2)	20	(87.0)	198	(73.3)		60	(70.6)	158	(76.0)		89	(72.4)	129	(75.9)
≥ 10000	76	(25.8)	3	(13.0)	72	(26.7)		25	(29.4)	50	(24.0)		34	(27.6)	41	(24.1)
Missing	104		10		94			29		74			40		63
ALP							0.138					0.023					0.344
< 300	217	(81.0)	19	(95.0)	197	(79.8)		53	(71.6)	163	(84.5)		85	(78.0)	131	(82.9)
≥ 300	51	(19.0)	1	(5.0)	50	(20.2)		21	(28.4)	30	(15.5)		24	(22.0)	27	(17.1)
Missing	131		13		117			40		89			54		75
Prior anemia							< 10-4					0.103					0.763
Grade 0	175	(44.8)	28	(84.8)	145	(40.7)		41	(38.0)	132	(47.1)		69	(42.3)	104	(45.2)
Grade 1-2-3-4	216	(55.2)	5	( 15.2)	211	(59.3)		67	(62.0)	148	(52.9)		89	(54.6)	126	(54.8)
Missing	8		0		8			6		2			5		3
CEA
n	307		23		282			90		215			126		179
Mean ± SD	455.3 ± 1979.3		43.7 ± 116.3		491.1 ± 2061.4		0.008	714.8 ± 2643		349.6 ± -1629.8		0.389	487.6 ± 1736.2		436.1 ± 2148.4		0.219
Median (min-max)	18 (0.1-20820)		5.7 (0.3-508.9)		19.4 (0.1-20820)			19.2 (0.1-18380)		15.6 (0.2-20820)			21.1 (0.4-14660)		15.4 (0.1-20820)
LDH
n	261		20		240			73		187			103		157
Mean ± SD	496.4 ± 860.1		299.6 ± 225.4		513.3 ± 892.8		0.282	506.7 ± 837.6		493 ± 873.1		0.374	530.8 ± 982.5		474.5 ± 774.8		0.244
Median (min-max)	233 (82-7230)		224 (117-878)		234 (82-7230)			249 (113-6190)		227 (82-7230)			248 (83-7230)		227 (82-6450)
Vital status							0.04					0.015					0.842
Death	311	(77.9)	21	(63.6)	288	(79.1)		98	(86.0)	211	(74.8)		128	(78.5)	181	(77.7)
Censored	88	(22.1)	12	(36.4)	76	(20.9)		16	(14.0)	71	(25.2)		35	(21.5)	52	(22.3)

WHO PS: WHO performance status; ALP: Alkaline phosphatase; CEA: Carcinoembryonic antigen; LDH: Lactate dehydrogenase.

Table 2 Treatment characteristics according to hematological toxicity in 399 consecutive patients with metastatic colorectal cancer n (%)

	All (n = 399)		Anemia (n= 397)				Neutropenia (n= 396)				Thrombopenia (n= 396)
			No (n= 33)		Yes (n= 364)		P	No (n= 114)		Yes (n= 282)		P	No (n= 163)		Yes (n= 233)		P
Lines of chemotherapy							0.3					< 10-4					0.053
< 2	46	(11.5)	2	(6.1)	44	(12.1)		25	(21.9)	21	(7.4)		25	(15.3)	21	(9)
≥ 2	353	(88.5)	31	(93.9)	320	(87.9)		89	(78.1)	261	(92.6)		138	(84.7)	212	(91)
Lines of chemotherapy
n	399		33		364			114		282			163		233
Mean ± SD	4.4 ± 2.5		5 ± 2.8		4.4 ± 2.5		0.266	3.4 ± 2.1		4.9 ± 2.6		< 10-4	3.9 ± 2.4		4.9 ± 2.6		< 10-4
Median (min-max)	4 (1-13)		4 (1-11)		4 (1-13)			3 (1-9)		5 (1-13)			3 (1-12)		5 (1-13)
Number of drugs							0.760					< 10-4					< 10-3
1	20	(5)	2	(6.1)	18	(4.9)		13	(11.4)	7	(2.5)		15	(9.2)	5	(2.1)
2	79	(19.8)	5	(15.2)	74	(20.3)		34	(29.8)	45	(16.0)		42	(25.8)	37	(15.9)
3	300	(75.2)	26	(78.8)	272	(74.7)		67	(58.8)	230	(81.6)		106	(65.0)	191	(82.0)
Bevacizumab							0.613					0.022					0.245
Yes	226	(57.1)	17	(53.1)	209	(57.7)		54	(48.2)	171	(60.9)		86	(53.8)	139	(59.7)
No	170	(42.9)	15	(46.9)	153	(42.3)		58	(51.8)	110	(39.1)		74	(46.3)	94	(40.3)
Missing	3		1		2			2		1			3		0
Anti- EGFR mab							0.789					0.004					0.096
Yes	165	(41.6)	14	(43.8)	150	(41.3)		34	(30.4)	130	(46.1)		59	(36.6)	105	(45.1)
No	232	(58.4)	18	(56.3)	213	(58.7)		78	(69.6)	152	(53.9)		102	(63.4)	128	(54.9)
Missing	2		1		1			2		0			2		0
Granulocyte-colony stimulating factor use							0.838					< 10-4					0.003
Yes	105	(26.7)	9	(28.1)	95	(26.5)		10	(9.2)	94	(33.5)		30	(18.8)	74	(32.2)
No	288	(73.3)	23	(71.9)	264	(73.5)		99	(90.8)	187	(66.5)		130	(81.3)	156	(67.8)
Missing	6		1		5			5		1			3		3
EPO use							0.049					0.57					0.41
Yes	76	(19.4)	2	(6.3)	74	(20.7)		23	(21.1)	52	(18.6)		34	(21.3)	41	(17.9)
No	316	(80.6)	30	(93.8)	284	(79.3)		86	(78.9)	228	(81.4)		126	(78.8)	188	(82.1)
Missing	7		1		6			5	(4.6)	2			3		4
Surgery of primary tumor							0.052					0.059					0.487
Yes	323	(81.2)	31	(93.9)	291	(80.2)		86	(75.4)	235	(83.6)		129	(79.6)	192	(82.4)
No	75	(18.8)	2	(6.1)	72	(19.8)		28	(24.6)	46	(16.4)		33	(20.4)	41	(17.6)
Missing	1		0		1			0		1			1		0
Surgery of metastatic site							0.148					0.007					0.001
Yes	102	(25.7)	13	(40.6)	103	(28.4)		22	(19.6)	94	(33.3)		33	(20.4)	83	(35.8)
No	295	(74.3)	19	(59.4)	260	(71.6)		90	(80.4)	188	(66.7)		129	(79.6)	149	(64.2)
Missing	2		1		1			2		0			1		1

GCSF: Granulocyte-colony stimulating factor; EPO: Erythropoietin.

Table 3 Univariate and multivariate analysis (Cox regression) of factors associated with overall survival in 399 consecutive patients with metastatic colorectal cancer

		Univariate analysisn= 399				Multivariate analysisn= 214
		HR	95%CI		P	HR	95%CI		P
Age					< 10-4
	≥ 75	1.77	1.33	2.35
Sex					0.615
	Male	1
	Female	1.06	0.85	1.33
Origin					0.04				0.0767
	Colon	1				1
	Rectum	0.75	0.57	0.99		0.68	0.44	1.04
WHO PS					< 10-4				0.021
	0	1				1
	1-2-3-4	2.15	1.63	2.82		1.53	1.07	2.19
CEA					< 10-4				0.143
	< 200	1				1
	≥ 200	2.31	1.72	3.09		1.37	0.90	2.09
Prior anemia					< 10-4				0.188
	No	1				1
	Yes	1.83	1.45	2.31		0.79	0.55	1.13
Anemia					0.005				0.029
	No	1				1
	Yes	1.91	1.22	2.98		2.19	1.08	4.41
Thrombopenia					0.003				0.036
	No	1				1
	Yes	0.70	0.56	0.88		0.69	0.49	0.98
Neutropenia					< 10-4				< 10-4
	No	1				1
	Yes	0.55	0.44	0.705		0.43	0.29	0.64
Metastatic sites					0.005				0.026
	1	1				1
	> 1	1.40	1.11	1.77		1.49	1.05	2.11
Surgery of the primary tumor					< 10-4				< 10-3
	No	1				1
	Yes	0.33	0.25	0.44		0.46	0.30	0.70
Surgery of metastatic site					< 10-4				< 10-3
	No	1				1
	Yes	0.27	0.21	0.36		0.48	0.31	0.74
ALP					< 10-4				0.007
	< 300	1				1
	≥ 300	3	2.16	4.18		1.81	1.18	2.78
LDH					< 10-4				< 10-3
	< 233	1				1
	≥ 233	2.15	1.62	2.85		2.03	1.38	2.97
Leucocyte count					< 10-4
	< 10000	1
	≥ 10000	2.04	1.53	2.73
Anti-EGFR Mab					0.006
	No	1
	Yes	0.73	0.58	0.91
Bevacizumab					< 10-4				0.107
	No	1				1
	Yes	0.61	0.49	0.76		0.76	0.55	1.06
Chemotherapy lines					< 10-4
	< 2	1
	≥ 2	0.46	0.32	0.66
Chemotherapy molecules					< 10-4
	1	1
	2	0.5	0.29	0.87
	3	0.35	0.21	0.58

WHO PS: WHO performance status; ALP: Alkaline phosphatase; LDH: Lactate dehydrogenase.