Colorectal Cancer: Open Access

A Comparison of Clinical Outcomes of Combination of Sorafenib and Cytotoxic Chemotherapy in Patients with Progression after Sorafenib; Initinal responder versus primary non responder

Recently regorafenib is approved as second line therapy in hepatocellular carcinoma (HCC) patients with progression after sorafenib in the basis of RESORCE study, but that was performed in patients with minimal duration of sorafenib usage above 4 months (initial responder, IR), then did not include patients with progression within 3 months (primary nonresponder; PN). We aimed to evaluate the efficacy and safety of using combination therapy of sorafenib and cytotoxic agent in patients with advanced HCC with progressive disease on sorafenib monotherapy; IR versus PN. Eligible advanced HCC patients with documented radiological evidence of disease progression with sorafenib treatment were recruited in our hospital from January 2011 to April 2017. All patients received doxorubicin at 60 mg/m2 every 3 weeks for a maximum of 6 cycles or tegafur/uracil 125mg/m2 twice daily with sorafenib for unlimited cycles. Twenty patients (IR; 9 patients, PN; 11 patients) were enrolled in the study. Doxorubicin was used in 5 patients (IR; 3, PN; 2) and tegafur/uracil was used in 15 patients. The median overall survival (OS) was 15 months (range 3.5-31) in IR, 7 months (range 4-14) in PN and the median progression-free survival (PFS) was 5 months (range 2-13) in IR, 3 months (range 2-9) in PN. Therefore OS and PFS in IR seem to be more longer than that in PN, but were not significant statistically (OS; 15 months versus 7 months, p-value=0.061, PFS; 5 months versus 3 months, p-value=0.136). Response rate in IR was followings; 2 partial response (PR), 6 stable disease (SD), that in PN; 2 PR, 5 SD. Especially, among 8 patients with complete remission of intrahepatic lesion (IR 5 patients, PN 3 patients), all patients achieved disease control (2 patients with PR, 6 patients with SD). Our study suggests that the combination of sorafenib and cytotoxic agent can be relatively effective strategy that achieves promising rates of local and systemic control in HCC patients refractory for sorafenib monotherapy despite of primary responsiveness. Moreover, it may be most effective for patients with complete remission of intrahepatic lesion.

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Author(s): Sang Youn Hwang

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