Page 86 - Read Online

Wada et al. Hepatoma Res 2018;4:8 I http://dx.doi.org/10.20517/2394-5079.2017.39 Page 3 of 8

Of 128 patients, 116 were diagnosed with HCC based on the results of a pathological examination. The
remaining 12 patients showed specific radiologic findings according to the criteria of the AASLD and
elevated serum a-fetoprotein (AFP) levels. No patients with differentiated intracholangiocellular carcinoma
and mixed-form liver cancer were included in this study.

Sorafenib was administered to patients with advanced HCC if: (1) they were not eligible for or their disease
progressed after surgery, locoregional therapy, or TACE; (2) their ECOG PS was 0-1; (3) their liver function
was classified as Child-Pugh A or B; and (4) they had adequate hepatic function (albumin > 2.5 g/dL, total
bilirubin < 3.0 mg/dL, and alanine aminotransferase and aspartate aminotransferase levels < 5 times the
upper limit of the normal range). Radiologic tumor progression was confirmed by contrast-enhanced
CT or MRI. The starting dosage of sorafenib was 800 mg/day p.o. However, considering the possibility
of having to discontinue sorafenib treatment at an early stage due to adverse events, the initial dosage
for patients with comorbidities was reduced to 400 mg/day. Moreover, the initial dosage for patients aged
≥ 75 years, those with a body weight ≤ 40 kg, and those with a history of treatment for varices or ascites was
200-400 mg/day. The dose was increased to the standard dose according to each patient’s tolerance.
Treatment was continued until tumor progression, unacceptable toxicity associated with sorafenib, or
withdrawal of consent. Second-line treatments after radiologic confirmation of PD included continuous
sorafenib treatment, even in palliative patients upon their request. However, patients with Child-Pugh C or a
PS > 2 at the time of confirmation of PD received best supportive care.

This study was approved by the Ethics Committee of the National Hospital Organization Kyushu Medical
Center and performed in compliance with the Declaration of Helsinki. All patients provided written
informed consent for sorafenib treatment.

Assessments
Tumor measurements were performed at baseline and every 2 months during treatment by contrast-
enhanced CT or MRI. Patients visited the clinic every 2 to 4 weeks to assess treatment compliance and
adverse effects. The survival status of the study participants was obtained from hospital records. Local
[15]
response was determined by the mRECIST criteria . We assessed the cause of progression (patterns of
progression) based on the following: 20% increase in tumor size against a known baseline lesion or the
emergence of a new lesion.

Follow-up
All patients were followed-up at our outpatient clinic according to a standardized protocol that included
tumor marker tests every month and MDCT or MRI every 8 weeks until the patient’s death or last visit.

Statistical analysis
Statistical analyses were conducted using the JMP version 11.0 software (SAS Institute, Cary, NC, USA).
Categorical variables were analyzed with the Chi-square or Fisher’s exact test, as appropriate. Continuous
variables were analyzed using the Student’s t-test or the Mann-Whitney U test, as appropriate. Time to
tumor progression (TTP), OS, and PPS were evaluated through the Kaplan-Meier method, and comparisons
between groups were performed using the log-rank test. Univariate and multivariate analyses were
performed using a Cox proportional hazards model and the backward elimination procedure. A P-value of
< 0.05 was considered significant.

RESULTS
Baseline characteristics of the patients
The average age of the 128 study participants (105 men and 23 women) was 68.9 years [Table 1]. Most
(n = 100) had a PS of 0. Regarding the preservation of liver function, 71, 43, and 14 study participants had