Toxicity
Treatment interruptions because of toxicity were 4% for FOLFIRI and 9% for FOLFOXIRI (P=0.19). No toxic deaths occurred, and two patients (1.6%) in each arm died within 60 days from the treatment start, all because of rapidly progressive disease. Most commonly observed toxicities were neutropenia, diarrhoea, nausea/vomiting, stomatitis, peripheral neurotoxicity, alopecia, and thrombocytopenia.r
Grade 3 to 4 toxicities, however, were uncommon except for neutropenia. In particular, the adverse events that occurred significantly more often in patients who received FOLFOXIRI were grade 2 to 3 peripheral neurotoxicity (0% v 19%; P<0.0001) and grade 3 to 4 neutropenia (28% v 50%; P=0 .0006). Nevertheless, the incidence of febrile neutropenia was comparable between FOLFIRI and FOLFOXIRI (3% v 5% of patients; P=0.75), and there were no episodes of documented infections; granulocyte colony-stimulating factor was used in 2% of FOLFIRI cycles and in 6% of FOLFOXIRI cycles. In four patients, oxaliplatin was interrupted because of grade 3 neurotoxicity (n=3) or allergic reaction (n=1).r
In the HCOG trial, there were two treatment-related deaths in the FOLFIRI arm and two in the FOLFOXIRI arm. All four treatment-related deaths were due to febrile neutropenia combined with diarrhoea. The death rates within the first 60 days of treatment were 2.7% (95% CI, 1.1–4.6%) for patients treated with the FOLFIRI regimen and 2.9% (95% CI, 1.3–5.3%) for those treated with the FOLFOXIRI regimen.r The reasons for the lack of survival benefit and more toxicities in the HCOG trial were the use of bolus 5FU in schedule and poor performance status. Only 36% of patients had ECOG performance status of 0 in the HCOG study compared to 61% in the GONO study. There were more ECOG 2 patients in the HCOG study compared to the GONO study (11% vs 2%).
Toxicityr
Grade 3/4 |
FOLFIRI
(n=122) % |
FOLFOXIRI
(n=122) % |
p-value |
Nausea |
1 |
6 |
NS |
Vomiting |
2 |
7 |
NS |
Diarrhoea |
12 |
20 |
NS |
Stomatitis |
3 |
5 |
NS |
Neurotoxicity |
0 |
2 |
<0.0001* |
Asthenia |
3 |
6 |
NS |
Thrombocytopenia |
1 |
2 |
NS |
Anaemia |
1 |
3 |
NS |
Neutropenia |
28 |
50 |
0.0006 |
Febrile neutropenia |
3 |
5 |
NS |
NS: not significant
*Grade 2-3