A review of the role of capecitabine in the treatment of colorectal cancer

Figures & data

Figure 1 Enzymatic conversion of capecitabine to 5FU.

Abbreviations: CE, carboxylesterase; CyD, cytidine deaminase.

Table 1 Summary of randomized trials comparing capecitabine with 5FU/LV (Mayo Clinic) regimen in metastatic colon cancer

Authors	No. pts	Regimen	RR (95% CI)	Median PFS	Median OS
Hoff et al 2001	605	Capecitabine 1250 mg/m^2	25.8	4.3 months	12.5 months
		twice daily for 2–3 weeks	(21.0%–31.2%)
		LV 20 mg/m^25FU 425 mg/m^2	11.6	4.7 months	13.3 months
		i.v. days 1–5 every 4 weeks	(8.2%–15.7%)	p = 0.72	p = 0.97
Van Cutsem et al 2001	602	Capecitabine 1250 mg/m^2	18.9	5.2 months	13.2 months
		twice daily for 2 of 3 weeks	(14.7%–23.8%)
		LV 20 mg/m^25FU 425 mg/m^2	15.0	4.7 months	12.1 months
		i.v. days 1–5 every 4 weeks	(11.1%–19.5%)	p = 0.65	p = 0.33

Abbreviations: 5FU, 5-fluorouracil; LV, leucovorin; OS, overall survival; PFS, progression-free survival; RR, response rate.

Table 2 Summary of randomized phase III trials about the combination of capecitabine plus oxaliplatin in metastatic colon cancer

Authors	No. pts	Regimen	RR	Median PFS	Median OS
Arkenau et al 2005	476	Oxaliplatin 70 mg/m^2 days 1 and 8 Capecitabine 1000 mg/ m^2 twice daily for 2 of 3 weeks or	47%	7.8 months	16.3 months
		Oxaliplatin 50 mg/m^2 LV 500 mg/m^2, 5FU 2000 mg/m^2 (infused over 24 hours), weekly for 4 of 6 weeks	49%	8.0 months p = 0.11	17.2 months p = 0.72
Massuti et al 2006	342	Oxaliplatin 130 mg/m^2 day 1 Capecitabine 1000 mg/m^2 twice daily for 2 or 3 weeks or	37%	8.9 months	18.8 months
		Oxaliplatin 85 mg/m^2 days 1 and 15 5FU 2.25 g/ m^2 48-hour i.v. infusion weekly for 6 weeks	45%	9.5 months p = 0.154	21.2 months p = 0.105

Abbreviations: 5FU, 5-fluorouracil; LV, leucovorin; OS, overall survival; PFS, progression-free survival; RR, response rate.

Figure 2 Flow chart of trial XELOX-1/NO16966.

Table 3 Comparative severe toxicity reported in the TREE-1 and TREE-2 trials (Hochster et al 2006)

Patients (%)	TREE-1 trial			TREE-2 trial
	mFOLFOX n = 49	bFOL n = 50	XELOX n = 48	mFOLFOX + bevacizumab n = 71	bFOL + bevacizumab n = 70	XELOX+ bevacizumab n = 72
Neutropenia	53	18	15	49	19	10
Dehydration	8	12	27	6	14	8
Diarrhoea	33	26	31	13	26	19
Hypertension	0	0	2	7	13	15
TE, arterial	2	0	0	0	0	3
TE, other	10	4	2	10	10	4
Nausea	16	14	19	6	11	11
Vomiting	14	10	19	1	13	10
Neurotoxicity	18	10	23	14	11	15
Hand-foot syndrome	8	2	19	0	0	10
Any grade 3/4	96	76	85	85	74	76

Abbreviations: TE, thromboembolic events.

Table 4 Comparative activity and toxicity of the assessed regimens before and after the addition of bevacizumab (Fuchs et al 2006)

Results	Without bevacizumab ± celecoxib			With bevacizumab ± celecoxib
	FOLFIRI n = 144	mIFL n = 141	CapIRI n = 145	FOLFIRI + bevacizumab n = 57	mIFL + bevacizumab n = 60
Response rate	47%	42%	38%	54%	53%
PFS months	7.6	5.8	5.5	9.9	8.3
OS months	23.1	17.6	18.9	NR	18.7
Diarrhoea	13%	19%	48%	11%	12%
Dehydration	6%	7%	19%	5%	2%
Neutropenia	40%	39%	31%	52%	29%
60-day mortality	2.9%	5.8%	3.5%	1.8%	6.8%

Abbreviations: OS, overall survival; PFS, progression-free survival.

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