The evidence supporting this protocol is provided by an open-label, multicentre, randomised phase III trial (CAIRO) involving 820 patients with advanced colorectal cancer.r
Between January 2003 and December 2004, patients were randomised to receive either first-line treatment with capecitabine 1250 mg/m2 BD for 14 days, second-line irinotecan 350 mg/m2 day 1, and third-line capecitabine 1000 mg/m2 BD for 14 days plus oxaliplatin 130 mg/m2 day 1 (sequential treatment; n=410) or first-line treatment capecitabine 1000 mg/m2 BD for 14 days plus irinotecan 250 mg/m2 day 1 and second-line capecitabine 1000 mg/m2 BD for 14 days plus oxaliplatin 130 mg/m2 day 1 (combination treatment; n=410). All treatment cycles were administered every 21 days. For patients above the age of 70, it was recommended to start irinotecan at 75% of the dose.r
The primary endpoint was overall survival and secondary endpoints included progression-free survival, tumour response, toxicity profile and quality of life.r
In a separate study, BICC-C trial, capecitabine plus irinotecan (CapeIRI) demonstrated a lower PFS compared with infusional 5FU/leucovorin/irinotecan (FOLFIRI) (5.8 vs 7.6 months; p=0.015). Higher rates of severe vomiting, diarrhoea and dehydration were also reported in the CapeIRI group.r However, the increase in toxicity may be explained by regional differences that have been observed for the tolerability of capecitabine.
Efficacy
In the CAIRO trial, the median overall survival was 16·3 (95% CI 14·3–18·1) months for the sequential treatment group and 17·4 (95% CI 15·2–19·2) months for the combination group. The hazard ratio for combination versus sequential treatment was 0·92 (95% CI 0·79–1·08; p=0·3281).r
Overall survival by treatment armr
© Lancet 2007
Toxicity
In the BICC-C study, CapeIRI (capecitabine/irinotecan) was associated with the highest rates of severe nausea, vomiting, diarrhoea, dehydration, and hand-foot syndrome. Discontinuation of study treatment for unacceptable toxicity was more common among patients treated with CapeIRI (26%) when compared with either FOLFIRI (15%) or mIFL (14%).r
Adverse Event
> Grade 3r |
FOLFIRI (n=137)
(%) |
mIFL (n=137)
(%) |
CapeIRI (n=141)
(%) |
Nausea |
9 |
7 |
18 |
Vomiting |
9 |
7 |
16 |
Diarrhoea |
14 |
19 |
48 |
Dehydration |
6 |
7 |
19 |
Neutropenia |
43 |
41 |
32 |
Febrile neutropenia |
4 |
12 |
7 |
Hand-foot syndrome |
0 |
0 |
10 |
FOLFIRI: infusional fluorouracil/leucovorin/irinotecan; mIFL: modified bolus irinotecan/fluorouracil/leucovorin; CapeIRI: capecitabine/irinotecan
© Journal of Clinical Oncology 2007