PHASE II STUDY OF S-1 MONOTHERAPY WITH APPLICATION OF DOSE-ADJUSTMENT BY CREATININE CLEARANCE IN CHEMONAIVE ELDERLY PATIENTS WITH ADVANCED NON-SMALL-CELL LUNG CANCER

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Abstract

Objective

The aim of this study was to evaluate the efficacy and toxicity of S-1, with adjusted doses based on body surface area (BSA) and creatinine clearance (Ccr), in chemonaive elderly patients with advanced non-small-cell lung cancer (NSCLC). Pharmacokinetic analysis was also carried out to evaluate the adequacy of the tailored S-1 dose.

Methods

Twenty-three patients with age 75 or older were enrolled from December 2007 to October 2009. S-1 was administered orally on days 1–28 twice daily (q42 days) until the first occurrence of disease progression, unacceptable toxicity or patient refusal. Doses of S-1 were adjusted based on individual Ccr and BSA. Pharmacokinetic studies were also carried out in 8 patients on day 7 of the first cycle. The primary objective is disease control rate (DCR; CR + PR + SD) and the secondary objectives are objective response rate (ORR), safety, overall survival (OS), progression-free survival (PFS) and clinical benefit rate (CBR; the rate of CR + PR + SD >24 weeks).

Results

The ORR was 8.7% (2/23), DCR was 69.6% (16/23) and the CBR was 30.4% (7/23). The median survival time (MST) was 228 days and the median PFS was 117 days. As for safety, grade 3/4 hematologic toxic effects have never been observed. As non-hematologic toxic effects, only one patient (4.3%) has experienced grade 3 anorexia and nausea/vomiting. In the pharmacokinetic study group (n = 8), the maximum plasma concentration (Cmax) and the area under the plasma concentration curve (AUC) of 5-FU were similar among eight patients irrespective of Ccr values which were comparable with the reported values in patients with normal renal function who received a standard dose of S-1 (80 mg/m2/day).

Conclusions

Our results suggest that tailored S-1 monotherapy is useful and tolerable as the first-line treatment in elderly patients with advanced NSCLC even when their renal functions are impaired.

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