Table 4.

Factors that altered the time to first occurrence of serious ADRs of interest

ADR	Factor	HR	95% CI	P value
Serious hand–foot skin reaction	Initial daily dose
	800 mg	1
	<800 mg	0.28	0.14–0.55	0.0002
	Sex
	Male	1
	Female	1.63	1.14–2.33	0.0075
	Age
	<65	1
	≥65, <75	0.67	0.46–0.97	0.0343
	Body weight
	<Median	1
	≥Median	0.66	0.47–0.93	0.0161
	ECOG PS
	0	1
	1	0.58	0.37–0.89	0.0137
	Bone metastasis
	No	1
	Yes	0.55	0.36–0.85	0.0066
Serious hepatic dysfunction	Initial daily dose
	800 mg	1
	<800 mg	0.50	0.29–0.85	0.01
	Hemoglobin
	<Median	1
	≥Median	1.81	1.28–2.54	0.0007
Serious hemorrhagic events	ECOG PS
	0	1
	1	1.85	1.26–2.71	0.0018
	≥2	2.84	1.49–5.43	0.0016
	Hemoglobin
	<Median	1
	≥Median	0.62	0.42–0.91	0.0159
	Renal comorbidity
	No	1
	Yes	2.01	1.19–3.38	0.0090
	Prior surgery
	No	1
	Yes	0.62	0.41–0.96	0.032

The following factors were used for multivariate analysis: initial daily dose, sex, age (<65, ≥65 to <75, ≥75), body weight (cut-off, male/female 60.9/50.0 kg), ECOG PS, metastatic status (lung only vs. others), metastases in bone, brain, liver, lung, kidney and others, ALT (17.0 IU/l), AST (20.5 IU/l), platelets (216 000/μl), creatinine (1.04 mg/dl), hemoglobin (11.6 g/dl), cardiac, hepatic, pulmonary and renal comorbidity, allergy, prior surgery and prior IFN-α.

CI, confidence interval.