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. 2022 Feb 19;27(5):371–379. doi: 10.1093/oncolo/oyab030

Table 4.

Incidence rate of grade 3/4 adverse events of special interest in each study and meta-analysis of risk difference.

Bi-weekly schedule Weekly schedule Pooled Risk Difference (%)a
Adverse events CECOGN = 77 NORDICN = 152 CELINEN = 60 OPTIMIXN = 99 APEC
(FOLFIRI)N = 101
APECN
(FOFOLX)N = 188
CECOGN = 75 NORDICN = 109 CRYSTALb
(CELINE)N = 303
CRYSTALb
(OPTIMIX)N = 303
CRYSTALb
(APEC)N = 303
CRYSTALb
(APEC)N = 303
Bi-weekly -Weekly Mean (95% CI)
Paronychia NR NR 18.3 NR 9.9 7.4 NR NR 4.6 4.3 4.7 4 6.2 [2.6, 9.7]
Neutropenia 36 40 NR 32 35.6 38.8 31 49 29.1 29.4 29.5 29.4 4.0 [−0.9, 8.9]
Diarrhea 10 9 0 13.1 11.9 8.5 8 16 12.5 14.6 14.7 14.2 −4.6 [−7.6, −1.7]
Rasha 17 9 8.3 NR 4 15.4 15 29 7.4 10.7 9.7 9.5 −3.1 [−11.1, 4.9]
Dermatitis acneiform 8 NR NR NR 5 1.6 4 NR NR NR 4.6 4.8 −1.0 [−3.5, 1.6]
Palmar-plantar Erythrodysesthesia Syndrome NR NR NR NR 2 4.3 NR NR NR NR 4 4.2 −0.8 [−3.4, 1.8]
Cardiopulmonary arrest NR NR NR NR 3 1.6 NR NR NR NR 7.2 5.5 −4.1 [−6.7, −1.5]
Hypomagnesemia 1 NR NR 1 NR NR 1 NR NR NR NR NR 0.7 [−1.4, 2.7]
Nail toxicity 6 2 NR 6.1 NR NR 8 6 NR 4.3 4.7 4 −1.2 [−4.6, 2.2]
Sepsis NR NR NR NR 4 2.1 NR NR NR NR 1.4 0.8 1.9 [−0.2, 4.0]
Acne-like rash 25 NR NR 15.2 10.9 18.6 19 NR NR 18.6 17.4 16.7 −1.0 [−5.2, 3.1]
Infusion related reaction 3 NR 1.7 0 0 4.8 3 NR 0.8 0.8 1.4 1.5 0.7 [−0.7, 2.2]

The estimated pooled risk difference is a weighted average effect size by sample size of each study through the selected studies.

The adverse events rates for CRYSTAL study presented on this table were adjusted to match with the baseline disease characteristics of study CELINE, OPTIMAX, APEC-FOLFIRI arm and APEC FOLFOX arm respectively.

Abbreviations: N, number of patients; NR, not reported.