Benefits and risks of palliative capecitabine based therapy to elderly patients with advanced colorectal cancer: Danish single centre experiences

Figures & data

Table I.  Gender, tumour characteristics and previous therapy according to age of patients with advanced colorectal cancer treated with capecitabine or XELOX.

	Capecitabine or XELOX								Capecitabine
	<70 years		≥70 years			70–74 years			<75 years		≥75 years
	(n = 203)		(n = 57)			(n = 37)			(n = 160)		(n = 18)
	no. (%)		no. (%)		P	no. (%)		P*	no. (%)		no. (%)		P
Chemotherapy
Capecitabine	135	(67)	43	(75)	–	25	(68)	–	160		18		–
XELOX	68	(33)	14	(25)		12	(32)		–	–	–	–
Age
Median, range	61	24–69	73	70–82	–	71	70–74	–	63	24–74	75	75–82	–
Gender
Male	114	(56)	35	(61)		23	(62)		86	(54)	10	(56)
Female	89	(44)	22	(39)	0.48	14	(38)	0.39	74	(46)	8	(44)	0.88
Primary tumour site
Ascendens	38	(19)	16	(28)	0.41	11	(30)	0.79	35	(22)	5	(28)	0.99
Transversum	10	(5)	4	(7)		3	(8)		10	(6)	1	(6)
Descendens	13	(6)	5	(9)		4	(11)		10	(6)	1	(6)
Sigmoid	71	(35)	15	(26)		9	(24)		47	(29)	5	(28)
Rectum	71	(35)	17	(30)		10	(27)		58	(36)	6	(33)
Tumour stage
Locally advanced	28	(14)	5	(9)	0.31	2	(5)	0.42	28	(17)	4	(22)	0.57
Metastasized	175	(86)	52	(91)		35	(95)		132	(83)	14	(78)
Liver	138	(68)	43	(75)		28	(76)		84	(53)	10	(56)
Lung	53	(26)	12	(21)		9	(24)		48	(30)	4	(22)
Tumour sites
1	75	(37)	22	(39)	0.69	11
2	90	(44)	26	(46)		18
≥ 3	38	(19)	9	(15)		8
							(30)	0.62	63	(39)	9	(50)	0.34
							(49)		76	(48)	8	(44)
							(21)		21	(13)	1	(6)
Tumour differentiation
Unknown	110	(54)	21	(37)	0.08	18	(49)	0.23	52	(33)	1	(5)	0.63
High grade	5	(3)	0	(0)		0	(0)		5	(3)	0	(0)
Intermediate grade	76	(37)	28	(49)		14	(38)		88	(55)	14	(78)
Low grade	12	(6)	8	(14)		5	(13)		15	(9)	3	(17)
Alk.Phosph. baseline
Median, range	279	45–1889	335	18–2560	0.06	412	77–2560	0.06	289	45–2560	266	18–1761	0.47
LDH baseline
Median, range	365	45–7629	376	131–3290	0.90	385	131–3290	0.90	432	45–7629	397	178–2173	0.73
Previous colon cancer
Synchronous	116	(57)	35	(61)	0.56	24	(65)	0.25	101	(63)	10	(56)	0.39
Metachronous	87	(43)	22	(39)		13	(35)		59	(37)	8	(44)
Previous therapy
Adjuv. chemotherapy	57	(28)	12	(21)	0.29	6	(16)	0.04	43	(27)	6	(33)	0.52
Radiotherapy	30	(15)	5	(9)	0.72	3	(8)	0.12	26	(19)	2	(11)	0.53

XELOX: Capecitabine and oxaliplatin, Alk.phosph.: Alkaline phosphatase, LDH: Lactate dehydrogenase. *compared to < 70 years.

Figure 1.  Progression free survival from start of palliative capecitabine or XELOX therapy for advanced colorectal cancer according to age < 70 and ≥70 years.

Figure 2.  Overall survival from start of palliative capecitabine or XELOX therapy for advanced colorectal cancer according to age < 70 and ≥70 years.

Figure 3.  Progression free survival from start of palliative capecitabine therapy for advanced colorectal cancer according to age < 75 and ≥75 years.

Figure 4.  Overall survival from start of palliative capecitabine therapy for advanced colorectal cancer according to age < 75 and ≥75 years.

Table II.  Response rates, tolerable dose as percent of standard dose and number of treatment courses according to age groups.

	Capecitabine or XELOX								Capecitabine
	<70 years		≥70 years			70–74 years			<75 years		≥75 years
	n = 203)		(n = 57)			(n = 37)			(n = 160)		(n = 18)
	(no. (%)		no. (%)		P	no. (%)		P*	no. (%)		no. (%)		P
Best response
CR	21	(10)	5	(9)	0.61	0	(0)	0.11	12	(7)	5	(28)	0.0006
PR	46	(23)	16	(28)		8	(22)		38	(24)	8	(44)
NC	74	(36)	19	(33)		13	(35)		57	(36)	5	(28)
PD	36	(18)	9	(16)		9	(24)		38	(24)	0	(0)
Not evaluated	26	(13)	8	(14)		7	(19)		15	(9)	0	(0)
Capecitabine% of standard dose
100%	127	(63)	31	(54)	0.47	22	(59)	0.55	102	(64)	7	(39)	0.22
75%	60	(30)	21	(37)		12	(32)		40	(25)	9	(50)
50%	16	(8)	5	(9)		3	(8)		18	(11)	2	(11)
Oxaliplatin% of standard dose
100%	42	(62)	10	(71)	0.87	8	(22)	0.83	–	–	–	–	–
75%	21	(31)	3	(21)		3	(8)
50%	4	(6)	1	(7)		0	(0)
Treatment courses
≤ 3	68	(34)	22	(39)	0.44	19	(51)	0.007	56	(35)	2	(11)	0.0003
4–6	80	(39)	21	(37)		16	(43)		57	(36)	4	(22)
7–9	41	(20)	9	(16)		2	(5)		34	(21)	7	(39)
10–12	14	(7)	5	(9)		0	(0)		13	(8)	5	28)
Courses to best response
≤ 3	68	(64)	21	(55)	0.78	15	(41)	0.32	66	(41)	6	(33)	0.002
4–6	28	(26)	11	(29)		5	(14)		30	(19)	6	(33)
7–9	8	(7)	6	(16)		0	(0)		8	(5)	6	(34)
10–12	3	(3)	0	(0)		0	(0)		3	(2)	0	(0)
Discontinuation
Toxicity	11	(8)	6	(14)	0.26	5	(14)	0.20	16	(10)	1	(6)	0.62
Non-compliance	2	(1)	0	(0)		0	(0)		2	(1)	0	(0)

*compared to < 70 years.

Table III.  Baseline and worst performance status and weight change during capecitabine based chemotherapy for advanced colorectal cancer according to age groups

	Capecitabine or XELOX								Capecitabine
	<70 years		≥70 years			70–74 years			<75 years		≥75 years
	(n = 203)		(n = 57)			(n = 37)			(n = 160)		(n = 18)
	no. (%)		no. (%)		P			no. (%)			P*	no. (%)		no. (%)		P
Performance status, baseline	131	(65)	27	(47)	0.17	17	(46)	0.08	89	(56)	8	(44)
0													0.59
1	56	(27)	25	(44)		16	(43)		54	(34)	9	(50)
2	16	(8)	5	(9)		4	(11)		17	(10)	1	(6)
Performance status, worst
0	68	(35)	12	(21)	0.68	7	(19)	0.003	48	(30)	4	(22)	0.38
1–2	102	(53)	35	(61)		20	(54)		89	(56)	14	(78)
3–4	15	(8)	5	(9)		5	(14)		20	(12)	0	(0)
5	7	(4)	5	(9)		5	(13)		3	(2)	0	(0)
Weight change
5% loss	19	(9)	6	(11)	0.94	6	(16)	0.60	21	(13)	0	(0)	0.004
− 5–5%	94	(46)	28	(49)		17	(46)		95	(59)	9	(50)
5–10% increase	29	(14)	12	(21)		7	(19)		22	(14)	5	(28)
10–20% increase	11	(5)	5	(9)		3	(8)		8	(5)	2	(11)
> 20% increase	2	(1)	1	(2)		0	(0)		2	(1)	1	(6)

*compared to < 70 years.

Table IV.  Worst CTC grade toxicity during capecitabine based chemotherapy of advanced colorectal cancer according to age of patients.

	Capecitabine or XELOX								Capecitabine
	<70 years		≥70 years			70–74 years			< 75 years		≥75 years
	(n = 203)		(n = 57)			(n = 37)			(n = 160)		(n = 18)
	no. (%)		no. (%)		P	no. (%)		P*	no. (%)		no. (%)		P
Anemia
Grade 1–2	57	(28)	22	(39)	0.20	14	(38)	0.38	64	(40)	7	(39)	0.34
Grade 3–4	2	(1)	0	(0)		0	(0)		1	(1)	0	(0)
Thrombocytopenia
Grade 1–2	25	(12)	9	(16)	0.31	5	(14)	0.92	5	(3)	0	(0)	0.42
Grade 3–4	0	(0)	1	(2)		0	(0)		0	(0)	1	(6)
Leucopenia
Grade 1–2	14	(7)	4	(7)	0.95	2	(5)	0.85	15	(9)	2	(11)	0.39
Grade 3–4	1	(0)	0	(0)		0	(0)		1	(1)	0	(0)
Infection
Grade 1–2	16	(8)	9	(16)	0.03	5	(14)	0.15	19	(12)	4	(22)	0.83
Grade 3–4	9	(5)	5	(9)		5	(14)		8	(5)	0	(0)
Nausia and vomiting
Grade 1–2	94	(47)	28	(49)	0.48	18	(49)	0.72	2	(1)	2	(11)	0.50
Grade 3–4	6	(3)	0	(0)		0	(0)		0	(0)	0	(0)
Mucositis
Grade 1–2	66	(33)	23	(40)	0.37	14	(38)	0.65	66	(41)	9	(50)	0.88
Grade 3–4	1	(1)	0	(0)		0	(0)		3	(2)	0	(0)
Diarrhoea
Grade 1–2	92	(46)	23	(40)	0.30	12	(32)	0.24	56	(35)	9	(50)	0.43
Grade 3–4	11	(6)	10	(18)		10	(27)		1	(1)	0	(0)
Cutaneous PPE
Grade 1–2	99	(50)	30	(53)	0.74	15	(41)	0.08	73	(46)	10	(56)	0.80
Grade 3–4	29	(15)	6	(11)		3	(8)		9	(6)	0	(0)
Myocardial ischaemia
Grade 1–2	3	(2)	3	(5)	0.57	2	(5)	0.86	4	(3)	1	(6)	0.98
Grade 3–4	4	(2)	0	(0)		0	(0)		4	(3)	0	(0)
Fatigue
Grade 1–2	147	(74)	45	(79)	0.06	27	(73)	0.06	4	(3)	1	(6)	0.95
Grade 3–4	11	(6)	4	(7)		4	(11)		4	(3)	0	(0)
Pain
Grade 1–2	26	(13)	5	(9)	0.93	4	(11)	0.89	117	(73)	16	(89)	0.81
Grade 3–4	0	(0)	0	(0)		0	(0)		12	(8)	0	(0)
Sensoric neuropathy
Grade 1–2	54	(27)	7	(12)	0.02	7	(19)	0.10	64	(40)	7	(39)	0.34
Grade 3–4	2	(1)	0	(0)		0	(0)		1	(1)	0	(0)

*compared to < 70 years.

Table V.  Summary of studies comparing efficacy and toxicity of capecitabine based chemotherapy for advanced colorectal cancer according to age.

Reference	Regimen	No.pt.	pts.by age	Age groups compared	Difference in efficacy	Difference in toxicity
						CTC grade 3–4
Present study	Cap.1250 mg/m^2 bid 2 weeks + / − Oxaliplatin 130 mg/m^2	260 pt.	57 pt.≥70 yr	<70 vs ≥ 70	Response rate:NS	NS
					Time to progression: Hazard ratio 1.09
Cassidy 2004 [9]	Cap.1000 mg/m^2 bid 2 weeks and Oxaliplatin 130 mg/m^2	96 pt.	48 pt.≥65 yr	<60 vs ≥60	Response rate: NS
				<65 vs ≥ 65		NS
Van Cutsem 2004 [11],	Cap.1250 mg/m^2 bid 2 weeks vs. 5-FU (Mayo)	Cap. 603 pt	716 pt.>60 yr	≥60 vs >60	Response rate:NS	NS
Cassidy 2002 [12]		5-FU 604 pt.			Time to progression: Hazard ratio 0.99
Bajetta 2004 [13]	Cap. 1000–1250 mg/m^2 bid 2 weeks and	140 pt.	Median 61 yr	<65 vs ≥ 65	Response rate: P = 0.02	NS
	Irinotecan 240–300 mg/m^2				Time to progression: Hazard ratio 1.00

Cap.:capecitabine, NS: not significant.

Cassidy J, Tabernero J, Twelves C, Brunet R, Butts C, Conroy T, et al. XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol 2004; 22: 2084–91

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Van Cutsem E, Hoff PM, Harper P, Bukowski RM, Cunningham D, Dufour P, et al. Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials. Br J Cancer 2004; 90: 1190–7

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Cassidy J, Twelves C, Van Cutsem E, Hoff P, Bajetta E, Boyer M, et al. First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann Oncol 2002; 13: 566–75

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Bajetta E, Di Bartolomeo M, Mariani L, Cassata A, Artale S, Frustaci S, et al. Randomized multicenter Phase II trial of two different schedules of irinotecan combined with capecitabine as first-line treatment in metastatic colorectal carcinoma. Cancer 2004; 100: 279–87

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