A phase II study of S-1 in combination with sorafenib in metastatic renal cell carcinoma.

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529 Background: The potential of S-1, an oral fluoropyrimidine derivative anticancer agent, for the treatment of metastatic renal cell carcinoma (mRCC) has been shown in two phase II studies. We therefore studied the efficacy and safety profile of S-1 in combination with sorafenib in Japanese patients with mRCC. The recommended dosage of this combination therapy was based on the results of an associated phase I study, presented at the 2012 Genitourinary Cancers Symposium (Abstract #447). Methods: In this phase II study, we enrolled patients with clear-cell or papillary carcinoma who had received no previous treatment or not more than 1 regimen of cytokine therapy. S-1 was administered orally at 80-120 mg/day according to body surface area for 28 consecutive days of a 42-day cycle in combination with sorafenib (800 mg/day) until disease progression. The primary endpoint was the objective response rate (ORR), reviewed by an independent review committee. Results: A total of 21 patients aged 41-78 years were enrolled and were fully assessable for efficacy and safety. Most patients (90.5%) had clear-cell carcinoma, and 8 (38.1%) had received prior cytokine treatment. The ORR was 52.4% (90% CI, 32.8-71.4). One (4.8%) of the 21 patients had a complete response to this combination therapy, 10 (47.6%) had partial responses, and 10 (47.6%) had stable disease. The median progression-free survival was 9.8 months (95% CI, 6.5-14.3). There were no deaths. This combination therapy was well tolerated, and most adverse events were grade 2 or lower. The most common grade ≥3 drug-related adverse events were hypophosphatemia (71.4%) and elevated lipase levels (33.3%). Conclusions: Combination therapy with S-1 plus sorafenib showed promising results regarding the primary endpoint of ORR and had an acceptable toxicity profile in patients with mRCC. Clinical trial information: JapicCTI-090973.