A randomized phase II study of a combination of docetaxel and S-1 versus docetaxel monotherapy in pts with NSCLC previously treated with platinum-based chemotherapy: Results of Okayama Lung Cancer Study Group (OLCSG) trial 0503

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8058 Background: Recent studies have demonstrated that docetaxel (DOC) monotherapy provides a significant survival prolongation in relapsed pts with NSCLC. However, its benefit remains modest and further improvement is needed. S-1 is a newly developed oral 5-fluorouracil derivative, possessing a promising anti-tumor activity in NSCLC. Based on a superior effect of combination of DOC and 5-fluorouracil derivative (capecitabine) to DOC alone in anthracycline-pretreated breast cancer pts, we conducted a randomized phase II study to evaluate the clinical significance of adding S-1 to DOC in the second-line setting. Methods: Pts with relapsed NSCLC to the first-line platinum-based chemotherapy were randomly allocated to DOC monotherapy (A arm; 60 mg/m2, day 1, q 3 wks) or a combination chemotherapy (B arm) of DOC (40 mg/m2, day 1, q 3 wks) and S-1 (80 mg/m2, days 1 to 15). The doses of arm B were determined based on the results of a phase I study conducted for Japanese pts with gastric cancer (Anticancer Res 24: 1843, 2004). The primary endpoint was response rate and secondary endpoints included OS, PFS and toxicity. Results: Between 2005 and 2008, 60 pts were enrolled (A/B: 29/31 pts). Demographics of the pts were as follows: M/F: 49/11, Ad/others: 40/20, ECOG-PS 0/1: 38/22. A median number of courses administered was 4 (range: 1 to 6). Objective response was obtained in 6 (20.7%) and 5 pts (16.1%) in arms A and B, respectively. With a median follow-up time of 16.9 months, MST and median PFST in arm A were longer than arm B (22.9 vs. 8.7 months and 3.7 vs. 3.4 months, respectively). The major toxicity was myelosuppression, with grade 4 neutropenia of 62% vs. 29%, whereas thrombocytopenia was generally mild. Grade 3 febrile neutropenia was observed in 4 and 1 pts, none of whom further developed grade 5 toxicity. Other grade 3 or greater non-hematological adverse events included fever (B: 1 pt), pneumonitis (B: 1 pt), liver dysfunction (B: 2 pts), skin rash (B: 1 pt), and all of them were improved with an appropriate supportive care. Conclusions: The trial suggests that docetaxel monotherapy remains a standard therapy for NSCLC pts who relapsed to platinum-based chemotherapy. No significant financial relationships to disclose.