Clinical Outcome and Prognostic Factors of Sorafenib in Japanese Patients with Advanced Renal Cell Carcinoma in General Clinical Practice

Abstract

Objective: Effects of sorafenib in general clinical practice, especially those with patients of Asian ethnicity, have been rarely investigated. We assessed efficacy, safety and prognostic factors for progression-free survival in Japanese patients receiving sorafenib for advanced renal cell carcinoma. Methods: We performed a retrospective analysis of 159 Japanese patients with renal cell carcinoma. Progression-free survival was estimated by the Kaplan -Meier method. Objective response (per Response Evaluation Criteria in Solid Tumors) and safety were assessed. Cox proportional hazards model was used to identify independent prognostic factors for progression-free survival. Results: The median progression-free survival was 9.0 months (95% confidence interval, 7.5 -10.6 months). In 142 patients with measurable lesions, the objective response rate was 21.8%, and disease control was achieved in 85 (59.9%) patients. Adverse events of any grade occurred in 152 patients (95.6%). Most common adverse events causing discontinuation or interruption of sorafenib were hand-foot skin reaction (22%), rash (10.7%) and liver dysfunction (10.7%). Dose reduction or therapy interruption due to adverse events was required in 128 patients (80.5%). Univariate and multivariate analysis revealed that favorable prognosis according to Memorial Sloan-Kettering Cancer Center prognostic factors and relative dose intensity during the first month of treatment of !50% were significant factors for predicting superior progression-free survival with sorafenib treatment. Conclusions: Sorafenib was effective in Japanese patients with advanced renal cell carcinoma in general clinical practice and was tolerated although most patients required dose reduction or interruption of therapy. Future studies should establish new strategies for treatment without sacrificing both efficacy and patient quality of life.

Efficacy and safety of sorafenib in advanced renal cell carcinoma patients: Results from a long-term study

“…The DCR obtained in our study was similar to that of previous studies (4,12,13). Concerning the median PFS time, significant differences existed in various reports.…”

“…However, in the current study, the results of the univariate analysis revealed that the grade of HFSR was not a predictive factor for tumor response to sorafenib. Compared with the TARGET study (4), our data indicated that the skin toxicity including HFSR in Chinese patients was much more frequent (60 vs. 33%) and more severe (26.7 vs. 6% with grade ≥3), as in the case of previous data obtained from Asia (11)(12)(13)22), and the resultant dose reduction may conceal the relevance between the grade of HFSR and the tumor response to sorafenib. A possible reason for the significant differences in the incidence of HFSR may include the difference in body surface area.…”

“…In another study on the treatment of sorafenib in 98 Chinese advanced RCC patients, the median PFS time was 60 weeks (13), which is very close to our data. In Japanese patients, PFS time was reported from 7.4 to 9 months (12,14). We considered different ethnic background as an important factor leading to these differences.…”

“…The dose of 600 mg per day may thus be a better choice than 400 mg per day to balance the safety against the efficacy of sorafenib in Asian patients with advanced RCC. Since there is a high incidence of dose reduction in Asian patients due to sorafenib-related adverse events (11)(12)(13)22), further studies are required to investigate the feasibility of such therapy regimens which show preference for a daily dose of 600 mg rather than 400 mg when the reduction of the initial dose (800 mg per day) is required.…”

CXCL10 and CCL2 mRNA expression in monocytes is inversely correlated with the HLA-DR lower fraction of monocytes in patients with renal cell carcinoma

“…Renal cell carcinoma (RCC) is known to be resistant to conventional chemotherapeutic agents and is known to induce an immunosuppressive environment. Although tyrosine kinase inhibitors (TKIs), including sorafenib and sunitinib, are widely utilized for the treatment of patients with metastatic RCC and TKIs are expected to act as adjuvants for immunotherapeutic effects (3,4), the anticancer effects of TKIs may be unable to overcome the immunosuppressive microenvironment of RCC hosts (5).…”